A STUDY ON ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN ELDERLY

submitted in partial fulfillment of the regulations

M.D., IN GERIATRIC MEDICINE

THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY

DEPARTMENT OF GERIATRIC MEDICINE

MADRAS MEDICAL COLLEGE

DISSERTATION ON

A STUDY ON ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN ELDERLY

submitted in partial fulfillment of the regulations

for the award of the degree of

M.D., IN GERIATRIC MEDICINEBRANCH – XVI

THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITYCHENNAI

DEPARTMENT OF GERIATRIC MEDICINE

MADRAS MEDICAL COLLEGE

CHENNAI – 600003

MAY 2018

A STUDY ON ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN ELDERLY

submitted in partial fulfillment of the regulations

M.D., IN GERIATRIC MEDICINE

THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY

DEPARTMENT OF GERIATRIC MEDICINE

MADRAS MEDICAL COLLEGE

CERTIFICATE

This is to certify that the dissertation titled “A STUDY ON

ASSOCIATION OF THYROID FUNCTION AND FRAILTY

IN ELDERLY” is the bonafide work done by

Dr. ARULMOZHISELVAN.V , Post Graduate Student, Department of

Geriatric Medicine, Madras Medical College, Chennai – 600003, in

partial fulfilment of the University rules and regulations for the award of

MD DEGREE in GERIATRIC MEDICINE BRANCH – XVI , under

our guidance and supervision, for the examination to be held on

May 2018.

Prof. Dr.G.S.SHANTHI, M.D.(Geriatrics),

Professor and Head,

Department of Geriatric Medicine,

Madras medical college,

Rajiv Gandhi Govt. General Hospital

Chennai – 600003

Prof. Dr. R.NARAYANABABU, M.D., D.C.H.,

Dean

Madras medical college,

Rajiv Gandhi Govt. General Hospital

Chennai – 600003

DECLARATION

I solemnly declare that this dissertation titled “A STUDY ON

ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN

ELDERLY” was done by me at Madras Medical College, Chennai –

600003,during the period February 2017 to July 2017 under the guidance

and supervision of Prof. Dr.G.S.SHANTHI, M.D.(Geriatrics), to be

submitted to the The TamilnaduDr.M.G.R. Medical University, towards

the partial fulfilment of requirements for the award of MD DEGREE IN

GERIATRIC MEDICINE BRANCH – XVI .

Place : Chennai Dr. ARULMOZHISELVAN.V,

Date : MD GERIATRIC MEDICINE,

Post Graduate Student,

Department of Geriatric Medicine,

Madras Medical College,

Rajiv Gandhi Govt. General Hospital

Chennai – 600003.

ACKNOWLEDGEMENT

I thank Prof. Dr.R.NARAYANABABU, M.D., D.C.H., Dean, Madras

Medical College, for permitting me to conduct the study and use the hospital

resources in the study.

I express my heartfelt gratitude to Prof. Dr.G.S.SHANTHI,

M.D.(Geriatrics), Professor and Head, Department of Geriatric Medicine, for

her inspiration, advice and guidance in making this work complete.

I also extend my sincere thanks to Prof. Dr.S.DEEPA, M.D., Associate

Professor, Department of Geriatric Medicine for guiding me duringthe study

period.

I am extremely thankful to Dr.K.UMA KALYANI, M.D., D.Diab.,

Assistant Professor, Dr.M.SENTHIL KUMAR, M.D., AssistantProfessor,

Dr.D.THANGAM, M.D., Assistant Professor and Dr.C.PRIYA MALINI,

M.D., D.Diab., Assistant Professor, Department of GeriatricMedicine, for

guiding me during the study period.

I thank my friend Dr.PADMANABAN, M.D., Biochemistry who has

helped me throughtout the study.

I thank our physiotherapists who has helped me in data collection.

I also thank all the postgraduate students, my colleagues and

paramedical staffs for their cooperation which enormously helped me in this

study. I am also indebted to thank all the patients and their caring relatives,

without whom this study would not have been possible.

Above all I thank the Lord Almighty for his kindness and benevolence

LIST OF ABBREVIATIONS AND SYMBOLS

TSH Thyroid Stimulating Hormone

fT4 Free Thyroxine

fT3 Free Triiodothyronine

UN United Nations

US United States

SRS Sample Registration System

WHO World Health Organisation

ATP Adenosine TriPhospate

MVO2 Max Maximal Oxygen Consumption

RMR Resting Metabolic Rate

ADL Activities of Daily Living

SHARE Survey of Health, Ageing and Retirement in Europe

↑ Increase

↓ Decrease

→ Leads to

↔ No change / equivocal

ROS Reactive Oxygen Species

TNF-α Tumor Necrosis Factor-α

PUFA Poly Unsaturated Fatty Acids

CP-II CarnitinPalmitoylTransferaseII

ALT Alanine Transaminase

HDL High density Lipoprotein

BNP Brain Natriuretic Peptide

S.D. Standard Deviation

LBW Low Birth Weight

DHEA DeHydroEpiAndrosterone sulphate

Vit D Vitamin D

GH Growth Hormone

IGF-1 Insulin like Growth Factor

CNS Central nervous System

CNTF CiliaryNeuroTrophic Factor

DM Diabetes Mellitus

CCF Congestive Cardiac Failure

LH Lutenising Hormone

FSH Follicle Stimulating Hormone

T Testosterone

E Estrogen

WBC White Blood Corpuscles

CD Cluster Differentiation

CCR5 C-C Chemokine Receptor 5

Il-6 Interleukin -6

CHS Cardiovascular Health Study

TUG Timed Up and Go test

SPPB Short Physical Perfomance Battery

SOF Study of Osteoporotic Fracture

BGS British Geriatric Society

GEM Geriatric Evaluation & Management

CGA Comprehensive Geriatric Assessment

PACE Program for All Inclusive Care for the Elderly

RAA Renin Angiotensin Aldosterone System

Vit-C Vitamin C

Ab Antibody

ACEIs Angiotensin Converting Enzyme Inhibitors

MIT MonoIodoThyronine

DIT DiIodoThyronine

TRH Thyrotrophin Releasing Hormone

TBG Thyroxine Binding Globulin

TTR Transthyretin

TRE Thyroid hormone Receptor Response Element

DNA Deoxyribo Nucleic Acid

RXR Retinoid X receptor

TR Thyroid hormone Receptor

CoA Co-Activator

Co-R Co-Repressor

mRNA Messenger Ribo Nucleic Acid

Na+ Sodium

K+ Potassium

Na+K+ ATPase Sodium Potassium Adenosine TriPhosphatase

FFA Free Fatty Acids

TGL Triglycerides

LDL Low Density Lipoprotein

BP Blood Pressure

MAP Mean Arterial Pressure

O2 Oxygen

CO2 Carbon di oxide

NHANES II National Health and Nutrition Examination Survey

Ca-ATPase Calcium ATPase

Na-K pump Sodium Potassium Pump

N Number of Samples

CKD Chronic Kidney disease

COPD Chronic Obstructive Lung Disease

BA Bronchial Asthma

CAD Coronary Artery Disease

CVA Cerebro Vascular Accident

CLIA ChemiLuminescentImmuno Assay

CES Center for Epidemiologic Studies

PASE Physical Activity Scale for Elderly

BMI Body Mass Index

SPSS Statistical Package for the Social Sciences

Std. Standard

Ft. Feet

Kg Kilogram

MrOS study Osteoporotic Fractures in Men Study

WHAS study Women’s Health and Aging Study

inCHIANTI

study Invecchiare in Chianti, aging in the Chianti area study

LIST OF FIGURES

Figure 1 Percentage distribution of population aged 65 and over by region:

2015 and 2050

Figure 2 Hypothesized levels of the syndrome of frailty(

Figure 3 Vicious Cycle of Energetic Frailty(1)

Figure 4 Phenotypic and index method

Figure 5 Mechanisms of sarcopenia

Figure 6 Hormones and frailty

Figure 7 Inflammatory and immunologic changes and frailty

Figure 8 Metabolic Causes of Frailty

Figure 9 Other risk factors for fraility

Figure10 Frailty trajectory

Figure 11 Thyroid hormones formation & secretion

Figure 12 Thyroid hormones structure

Figure 13 Regulation of thyroid hormone secretion

Figure 14 Thyroid hormone action

Figure 15 Hand grip dynamometer

LIST OF CHARTS

Chart 1 Decadal growth in elderly population in relation to that of general

population

Chart 2 Vulnerability of frail elderly people to a sudden, change in health

status after a minor illness

Chart 3 Pathway towards frailty, disability and death.

Chart 4 Age distribution in total

Chart 5 Sex distribution in total

Chart 6 Frequency distribution of frailty phenotype categories

Chart 7 Prevalence of individual components of frailty phenotype criteria

Chart 8 Frequency distribution of individual components of frailty phenotype

Chart 9 Frequency distribution no. Of components of frailty phenotype

Chart 10 Median age of study groups

Chart 11 Age distribution among the study groups

Chart 12 Sex distribution among the study groups

Chart 13 Median bmi of study groups

Chart 14 Bmi distribution among the study groups

Chart 15 Median hand grip of study groups

Chart 16 Median 15 ft walking time of study groups

Chart 17 Median pase score of study groups

LIST OF TABLES

Table 1 Percentage share of elderly population aged 60 and above

to total population

Table 2a Life expectancy at birth

Table 2b Life expectancy at birth and at old age in India

Table 3a Phenotypic and index method

Table 3b Phenotypic and index method

Table 4 Risk factors of Sarcopenia

Table 5 Thyroid hormones action on metabolism

Table 6 Aging Changes of Thyroid Gland

Table 7 Hormonal changes in thyroid dysfunction

Table 8 Summary of studies on thyroid abnormalities and frailty.

Table 9 Criteria Used to define Frailty

Table 10 PASE Scoring

Table 11 Age distribution in total

Table 12 Sex distribution in total

Table 13 Frequency distribution of Frailty Phenotype Categories

Table 14 Prevalence of individual components of frailty phenotype

criteria

Table 15 Frequency distribution of individual components of frailty

phenotype

Table 16 Frequency distribution of no. Of components of frailty

phenotype

Table 17 Total Descriptives of other characteristics of the study

sample

Table 18 Median age of study groups

Table 19 AGE DISTRIBUTION AMONG THE STUDY GROUPS

Table 20 SEX DISTRIBUTION AMONG THE STUDY GROUPS

Table 21 Descriptives of baseline characteristics & their significance

Table 22 Median BMI of study groups

Table 23 Median hand grip of study groups

Table 24 Median 15 ft walking time of study groups

Table 25 Median PASE score of study groups

Table 26 Correlation between BMI and ft3,ft4 & TSH

Table 27 BMI category vs ft3,ft4 , TSH

Table 28 Frailty categories vs ft3 , ft4 , TSH

Table 29 THYROID FUNCTION CATEGORY * FRAILTY

CATEGORY

Table 30 Individual components of frailty phenotype and

ft3,ft4,TSH

Table 31 Correlations between individual components of frailty

phenotype and ft3 ,ft4 and TSH

TABLE OF CONTENTS

Sl.no. CONTENTS Page no.

1 INTRODUCTION 1

2 AIM AND OBJECTIVES 5

3 REVIEW OF LITERATURE 6

4 MATERIALS AND METHODS 63

5 RESULTS 71

6 DISCUSSION 99

7 STRENTHS AND LIMITATIONS 103

8 CONCLUSION 104

9 BIBLIOGRAPHY

10 PROFORMA

11 INFORMATION SHEET

12 CONSENT FORM

13 ETHICAL COMMITTEE APPROVAL FORM

14 URKUND ANALYSIS RESULT

15 ANTI PLAGIARISM CERTIFICATE

16 ANNEXURES

a) QUESTIONNAIRE FOR PASE

(PHYSICAL ACTIVITY SCALE FOR ELDERLY)

b) ACTIVITY CATEGORIES FOR PASE

c) TO COMPUTE A PASE SCORE:

d) SOF CRITERIA FOR FRAILTY

e) CLINICAL FRAILTY SCALE

f) PRISMA-7 QUESTIONNAIRE

g) EDMONTON FRAIL SCALE

17 MASTER CHART

INTRODUCTION

1

INTRODUCTION

Worldwide the elderly population growth is remarkably increasing

due to improvement in life expectancy, better availability of Basic Health

Care services and advanced medical care and improvement in socio

economic status. According to 2011 Census the share of population aged

≥60 years is 8% in India and in Tamilnadu it is 10.5%(3).

William Shakespeare in his work “as you like it; act II, scene VII”

said, “the SIXTH age shifts into the lean and slipper'd Pantaloon, With

spectacles on nose and pouch on side; his youthful hose, well sav’d, a

world too wide for his shrunk shrank; and his big manly voice, Turning

again toward childish treble, pipes and whistles in his sound”(4). Aging is

an inevitable event after birth. Surprisingly the fastest growing section of

most population, worldwide is the oldest old i.e., those aged >= 80 yrs.

and above, especially in developing countries like India and China. Not

everyone can age successfully.

According to Dorothy Thompson, “age is not measured by years.

Nature does not equally distribute energy some people are born old and

tired while others are going strong at 70”(5). There is heterogeneity in the

aging process and it varies from individuals to individuals(6). Meanwhile

some underlying genetic and environmental factors will lead a proportion

of elderly population to experience chronic diseases or conditions,

2

disability, decreased functional capacity, decline in cognition and will

disengage them with life due to complex mechanisms(6–8).

As a novel attempt, to explain the heterogeneity of aging in elderly

population, the concept of frailty has evolved and the conceptual

knowledge about frailty is vital for clinical practitioners and policy

makers(9).The term “Frailty” is used to characterise the weak and

vulnerable subgroups of older adults(10)(11). Frailty is a compelling

concept and it forms the central core of geriatric medicine.

Frailty is a specific entity and is described in Literature as a

“biological syndrome of increased vulnerability to adverse health

outcomes which has been triggered by minor stressors due to poor

resolution of homeostasis as a consequence of age-related decline across

many physiological systems(12).” It can be shortly said as “an expression

of the lack of adaptive capacity of the organism(13)”. So the elderly frail

are visibly more vulnerable, withdrawn, unsteady and weak due to less

efficient network of homeostasis and they are at increased risk of adverse

outcomes like disability, dependence, recurrent hospitalization,

institutionalization, falls, injuries, and acute illness, delayed recovery

from illness, delirium, iatrogenesis & decreased survival. The condition

“Frailty” can exist independently of age, disability and chronic diseases

and may be an independent physiologic process involving multiple

3

systems(11). Although the general tendency for older adults is to get

worse than to improve, there is evidence that frailty can be resisted &

older people can regain at least some functioning i.e., it can be reversed

or delayed(14)(15). The cornerstone of geriatric medicine concerns the

early identification, evaluation and treatment of frail elderly and

prevention of loss of independence and disability. However little is

known about the development and progression of frailty.

Neuromuscular, endocrine, inflammatory & immunologic changes

which occur with aging, oxidative stresses have been implicated in the

genesis and progression of frailty. Body composition which in turn is

determined by lean body mass (muscle mass & visceral organs) plays a

vital role in the health of elderly. Muscle mass & strength are decreased

in thyroid disorders like hyperthyroidism (thyrotoxic myopathy) and

hypothyroidism (muscle weakness).

Moreover, the symptoms of hyperthyroidism (weight loss, muscle

weakness, exhaustion) and hypothyroidism (muscle weakness, fatigue,

reduced muscle strength, loss of appetite) have resemblance to that of

frailty phenotype. However these symptoms are often overlooked in

elderly. Also Subclinical dysfunctions of thyroid are common in elderly

and patients with subclinical thyroid dysfunction don’t manifest these

overt symptoms.

4

Subclinical thyroid dysfunctions have been associated with various

adverse health outcomes(16–22). All these adverse outcomes might have

direct or indirect relationship with frailty. Hence we propose this study to

investigate into the relationship between thyroid function and frailty in

elderly individuals by hypothesizing that slight differences in thyroid

hormones and TSH in elderly individuals are associated with frailty and if

significant relationship is found to have existed, it helps in management

of frail individuals.

AIMS AND OBJECTIVES

5

AIMS AND OBJECTIVES

AIM:

To investigate into the relationship between Thyroid Function and

Frailty in elderly.

OBJECTIVES:

By simple random sampling, selecting 200 patients and categorize

them as frail, intermediate/pre-frail, non-frail/robust by applying Fried's

Frailty Phenotype criteria.

1) To find the prevalence of Frailty in OP and IP patients attending a

tertiary care centre.

2) To do Thyroid Function Test to find association between fT4,

fT3,TSH levels and Frail, Pre-frail, Robust/Non-frail Category.

3) To find correlation between fT4, fT3, TSH and individual

components of Frailty Phenotype Criteria

REVIEW OF LITERATURE

6

REVIEW OF LITERATURE

DEFINITION OF ELDERLY

Definition of elderly is arbitrary. There is no standard United

Nations numerical criterion. However “the cut-off of 60 years and above

is agreed by UN for defining elderly.” >65 years of age is considered by

most developed countries to define the older population

(23).Conventionally, “the chronological age of 65 years and above is

depicted as the Cut-off for elderly(24).” National policy on Older persons

defines “Elderly as the citizens who have crossed the age of 60 years and

above in India(25).”

DEMOGRAPHICS OF ELDERLY

Global Scenario

At a faster rate, the global population is growing old, owing to

decreased fertility, improving health and longevity. Remarkably, there is

great rise in elderly population at never before seen rate. 562 million

people (8%) constituted the elderly population >65 years, when world

population reaches 7 billion in 2012. 3 years after the elderly population

rose by 0.5% i.e., 617 million, 8.5% of total population. This rising trend

in older population is because of US and European baby boomer

7

generations post world war and also due to a novel increase of elderly

population in Latin America and Asia(26).

Japan remains as the World’s oldest country because 26.6% of

Japan’s population are above the age of 65.The Graying nations

succeeding Japan are Germany, Italy, Greek and many other European

countries. By 2050, the older population aged 65 and above is estimated

to be 39% of the total population in Japan and the world will continue to

view Japan as the oldest country. The other Graying nations estimated to

be the successors of Japan in order are South Korea (35.9%), Hong Kong

(35%), Taiwan (34.9%) and other European countries(26).

Variations exist between different countries and countries with

respect to onset and duration of the stages of demographic transition. The

transition was started in the more developed countries like Western and

Northern countries of Europe and Japan in the last century itself and this

transition took decades to complete in many countries. This process of

demographic transition has found its inception in less developed countries

in Latin America and Asia in recent decades. However the transition

occurs more rapidly(27).

8

Figure 1 percentage distribution of population aged 65

and over by region: 2015 and 2050

DEMOGRAPHIC TRANSITION

8.5% of population aged over 65 is expected to increase by 12.1%

in 2030 and 18.8% in 2015 in Asia. From 2015-2050, the oldest

population in 23 Asian countries is estimated to be quadrupled(26). Due

to increasing life expectancy at older ages, Elderly population aged or

over 80, about 126.5 million globally in 2015 is going to be tripled

around 446.6 million(28).

The oldest old (80 and above) are different from rest of the older

population and are likely to have problems which needs long-term care.

More public resources will be consumed by them and there will be a

hefty burden for families in providing informal care(29).

9

By 2020, elderly population is going to be more than children

under age 5 populations historically for the first time. In 2050, the

proportion of world’s population aged 65 and above is estimated by UN

to be doubled from 7.6% presently to 16.2% (28).

China and India, the two population giants are in different path of

aging mainly because of varied fertility trends and methods of family

planning. China’s share of older population aged 65 and above is 10.1%

whereas India shares only 6 percent and the share by China is expected to

double by 2030 to 238.8 million (17.2%) of Total Population.

Indian Scenario

As per census 2011, India’s total population was 1210.9 million

with elderly above 60 years contributes 8.6% to total population i.e.

around 103.9 million with 51.1 million are elderly males (8.2%) and 52.8

million are elderly females (9%) with respect to residence, the proportion

of rural elderly population was 8.8%. In urban areas it was 8.1

percent(30).

10

Table 1 Percentage share of elderly population aged 60 and above

to total population(30)

Census Person Male Female Rural Urban

1961 5.6 5.5 5.8 5.8 4.7

1971 6.0 5.9 6.0 6.2 5.0

1981 6.5 6.4 6.6 6.8 5.4

1991 6.8 6.7 6.8 7.1 5.7

2001 7.4 7.1 7.8 7.7 6.7

2011 8.6 8.2 9.0 8.8 8.1

The percentage share of elderly to total population of India since

1961 rose by 3 percent in 2011 and this proportion of elderly is projected

to rise to 10.7 percent by the year 2021(30)

11

Chart 1 Decadal growth in elderly population in relation to that of

general population (28)

Till 2001, there is a decreasing trend in the decadal growth in

elderly population like that of general population. In the last one decade

(2001-2011), the growth in elderly population rose to 36 percent from 25

percent in the earlier decade.

According to population census 1991, the elderly males exceeded

in number than that of elderly females. Interestingly reversal of trend has

been observed. The female elders outnumbered the male. Comparing to

elderly male, elderly females are more vulnerable which policy makers

should concern (30)

12

State Wise Scenario

According to census 2011, South Indian State Kerala has the

highest proportion of elderly aged 60 and above (12.6%).Following

Kerala, Goa has 11.2% and Tamilnadu has 10.4%.The increased

proportion in these states is because of the declining fertility increasing

longevity and better medical facilities available. North East States like

Meghalaya, Arunachal Pradesh have less than 5% of elderly

population(31)

Life Expectancy at Birth

Table 2alife expectancy at birth(32)

2015 Expected at 2050

World General Population 68.6 76.2

Female 70.7 78.8

Male 66.6 73.7

Asia General 71.0 78.5

Female 73.0 81.1

Male 69.1 76.0

(Source :US Census Bureau, 2013; International Data Base)(32)

13

As of 2015, life expectancy at birth is >80 years for 24 countries

with Japan, Singapore, Hong Kong in the leading list.

In United States life expectancy at older ages in 2009 has increased

to 19.1 years from 11.9 years in 1900. Amidst the same period, the life

expectancy at age 80 has increased to 9.1 years from 5.3 years(33). Even

countries, like Afghanistan with lowest life expectancy at older ages are

also projected to see improvement with 11 years to 13 years for male by

2050, 12.1 year to 15 years for female during the same period for Afghan

elderly aged 65 years above(26).

In Indian rural areas, life expectancy at birth has increased to 66.3

years in 2009-2013 from 48 years in 1970-75.Whereas in urban areas the

increase is from 58.9 years to 71.2 years.

LIFE EXPECTANCY

Table 2b life expectancy at birth and at old age in india(34)

India

At Birth At old age

1970-75 2009-2013 1970-75 2009-2013

Rural 48 66.3 13.5 17.5

Urban 58.9 71.2 15.7 19.1

Source : Census SRS Statistical Report 2013(34)

14

In India

Kerala has the highest life expectancy at birth, 71.8 years for men

and 77.8 years for women, followed by Maharashtra and Punjab. Punjab

has the highest life expectancy at the age of 60 years (19.3 years) for

males followed by Himachal Pradesh (18.3 Years) and Kerala (18 years)

and it is lowest for Assam and Madhya Pradesh (15.4 years).For women,

Kerala has the highest life expectancy at the age of 60 years (21.6 years)

and Bihar has the lowest (17.5 years)(30).

The increase in life expectancy is due to falling tobacco use among

male population and decreasing cardiovascular mortality in both male and

female population. Other contributing factors are improvements in

housing, sanitation, nutrition, the control of infectious diseases and

maternal mortality and the advent of antibiotics and vaccination(14).

However, disability free life expectancy is not increasing as fast as

life expectancy in many countries. Hence measures to achieve better

living in addition to longevity have to gain the momentum.

To live with dignity and with optimum health are fundamental

rights of an individual and elderly are no exception. The supreme aim in

elderly care is to maintain their functional status. For this the best strategy

is to move from recovery from disability (Recovery is difficult when

15

there is already established disability) to avoiding the decline of

functional status shortly prevention from disability(35).

There are some questions to answer: Whether disability is

avoidable? Is disability an unavoidable consequence of the aging

process? The available data support the answer that disability can be

avoided (36),(37).

In short, the challenge for the future is to prevent or delay

disability? To face this challenge, the focus should be on the people at

risk. In the past, the people at risk were thought to have chronic diseases

as they are the most common factor in adverse outcomes of health. But

chronic diseases do not seen to be an appropriate predictor in older

people.

By 1980, the concept of frailty found its origin and it’s gaining

acceptance as a predictor of morbidity and mortality. There is no

universally accepted definition of frailty. As per Fretwell statement in

1990, “Frailty in an individual is defined as an inherent vulnerability to

challenge from the environment”. In 1993, according to W.Bortz, “active

life expectancy is threatened by the development of frailty.”

In the mid-to-late 1990s Rockwood and colleagues proposed that

frailty be defined as a state in which there was a dependence on others for

16

performing function of daily living. Later this group developed a Frailty

Index, a longer Clinical Frailty Scale and a brief screening tool known as

frail(10).

DEFINITION OF FRAILTY

Frailty is theoretically defined as a clinically recognizable state of

increased vulnerability resulting from aging- associated decline in reserve

and function across many physiological systems such that the ability to

cope with everyday or acute stressors is compromised(38).

Fried and colleagues defined it “as a biologic syndrome of

decreased reserve and resistance to stressors, resulting from cumulative

decline across multiple physiologic system and causing vulnerability to

adverse outcomes(12).”

As per world report on aging and health, by WHO(39) , “the

definition of frailty remains contested , but it can be considered as a

progressive age-related decline in physiological systems that results in

decreased reserves of intrinsic capacity , which confers extreme

vulnerability to stressors and increases the risk of a range of adverse

health outcomes”.

17

FRAILTY IS AT THE CORE OF GERIATRIC MEDICINE

Frailty forms the central core of geriatric medicine(38) for the

following reasons

� Frail elders are at risk for adverse outcomes of health like

disability, dependency, institutionalization, injuries, falls, poor

tolerance to hospitalization and invasive procedures, acute illness,

prolonged recovery from illness or hospitalization and the

mortality rate is being high in these individuals. And there is high

risk of iatrogenicity.

� They are in high need of health care resources.

� Caring those at risk people needs increased costs and it consumes

time and the caring requires special expertise skills.

� The prevalence of frailty increases with increase in age.

� Severity of Frailty spans from subclinical to a clinical stage to

impending death and it underlies the heterogeneity of health status

in elderly.

� With increasing age, there is increased vulnerability to multiple

diseases with no evident pathogenetic connections. Such

18

vulnerability is not explained by changes in recognizable risk

factors and can be attributed to poor homeostatic equilibrium.

� Diseases alone or in combination are not enough to explain

functional outcomes in elderly.

� Disease independent age related alterations in the reserve and

associated physiologic vulnerabilities is associated with variable

effects to treatments.

� Frailty is a condition of impending deterioration in health and

functional status and it requires attention to prevent disability and

other associated outcomes and it needs expert skills to diagnose

intervene frail elders.

� In most countries, health care cost, reimbursement is based on

specific diagnostic categorization and treatment and the

reimbursement is not based on presence or absence of frailty or

frailty even in the absence of disease.

But specialized geriatric care (expert care) needs a greater real cost

of caring. Redesign of care and reimbursement will match the needs,

improve the outcomes and balance the overall costs.

19

THEORIES OF FRAILTY(1)

1) Rockwood posits deficit accumulation theory

According to this, frailty results from accumulation of potentially

unrelated diseases, subclinical dysfunctions and disability across organs,

parts and system of the body. A simple count of all deficits (symptoms,

signs, disease, geriatric conditions, laboratory abnormalities, disabilities)

leads to a close response relationship with mortality.

2) Unique pathophysiologic process

Frailty is due to a primary defect in basic biologic system (energy

production, distribution and utilization) which in turn affects key

physiologic systems (neuroendocrine, inflammatory and immunologic

processes) leading to a short circuit in the homeostatic regulatory network

in which each system have mutual effect on each other and compensate to

a degree when any one is impaired. Compromised homeostasis results in

increased vulnerability to adverse outcomes triggered by minor

stressors(1).

20

Figure 2 hypothesized levels of the syndrome of frailty(1)

3) Energetic Pathway of Frailty

Every living cell needs energy for its life and this energy is

acquired in the form of phosphate release from ATP. ATP is stored only

for 6 sec. Neverthless ATP is constantly resynthesized to maintain the

harmony. ATP can be synthesized both by aerobic and anaerobic

pathways. Most energy generated in our body is through aerobic

metabolism (maximum oxygen consumption -MVO2 max that energy

21

generated in a time unit). Large amount of energy produced is spent in

resting metabolic rate - to maintain homeostatic equilibrium.

Normally, an extra amount of energy is needed for compensatory

mechanisms to balance the unstable homeostasis caused by pathologies

(Homeostatic effort). The remaining energy is spent for cognitive and

physical activities. Elderly who are unhealthy and with chronic disease

have a higher RMR than people of same age and sex. Homeostatic effort

is increased rapidly with health status deterioration and with increasing

work load, the individual starts experiencing fatigue within the range of

energy used for physical activity as most energy is usually spent in

performing basic ADLS and they feel exhausted and ultimately land up in

sedentary existence (decreased physical activity) and in long term the

total amount of energy produced is reduced thereby triggering a vicious

cycle, leading to progressive, accelerated decline in physical

junction(1)(40).

22

Figure 3 Vicious Cycle of Energetic Frailty(1)

OPERATIONAL DEFINITIONS

To provide frail elderly patients the care they used, it is foremost

important to identify Frailty with a proper diagnostic criterion. However

there is no gold standard criterion to define frailty. In an attempt to

standardize the definition of Frailty, Fried et al (2001) proposed the

“phenotypic method(12).” Later Rockwood and colleagues proposed the

“Index Method(40).”

23

Figure 4 phenotypic and index method

Table 3a phenotypic and index method

Frailty Phenotype Frailty Index

Qualitative Quantitative

Rules based method Index Based method

Several specific signs and

symptoms are defined which

together from a geriatric

syndrome

Based on counting of number of

health deficits.

Excluded the presence of

disease and disability

Includes disease and disabilities along

with symptoms, signs and lab values

Clinically recognizable. Helps

in recognizing the biological

nature of frailty not interfered

with disease or disability .

Attractive mathematical model that

support the idea of reduced

homeostatic reserve. “The more

deficits, the individuals have

24

Frailty Phenotype Frailty Index

accumulated the more likely they are

to be frail”.

categorically defines the

presence/ absence of a

condition of risk for

subsequent adverse events

Allows frailty to be graded rather than

present or absent

Cognitive impairment which

has been associated with

functional decline and

disability is not taken into

account.

More sensitive predictor of adverse

outcomes like worsening health status,

rate of institutionalization and death

because of its finer graded risk scale.

Table 3b phenotypic and index method

Phenotypic Method Index method

Frailty status is identified by

the occurrence of atleast 3 of

the following 5 phenotypes

1. Unintentional weight loss

2. Poor hand grip strength

3. Self reported

exhaustion(s/o poor

endurance & low energy)

4. Slow gait speed

5. Low physical activity

Frailty status has been marked as a

state at risk caused by accumulation of

deficits, which has been counted and

an index is derived from the

information gathered from

Comprehensive Geriatric Assessment.

Frailty Index =

No. of Deficits in an individual

---------------------------------------

Total No. of deficits measured

25

Phenotypic Method Index method

Frailty phenotypic method

takes approximately only 10-

20 min to ascertain the frailty

status and it might serve as a

basis for detection of frailty

in routine care to predict and

prevent the adverse outcomes.

Biologically rooted and

affords a pathophysiological

understanding of frailty.

Despite it’s a sensitive indicator in

predicting adverse outcomes

individually large no. of information

around 70 items collected and they

make the approach less attractive in

clinical practice and primary care (time

consuming).

Also the inclusion of co-morbidity and

disability in this method impairs the

use of frailty index in prevention.

The diffuse set of impairments

amalgamated by the FI is not amenable

to targeted therapeutic interventions.

Both the above methods have considerable overlap in identifying

frailty and demonstrate a convergence in predicting adverse outcomes.

Those two different models should be considered complimentary in the

evaluation of the older person.

Regardless of the definition, literature shows that frail elderly

persons have changes in the 4 main domains of the aging phenotype

namely body composition, homeostatic dysregulation, energetic failure,

and neurodegeneration(40).

26

EPIDEMIOLOGY

Global epidemiology

There are many epidemiologic studies of frailty and there are

discrepancies in data on frailty prevalence which can be attributed to

different operational definitions of frailty inclusion or exclusion criteria,

study population and the study setting. Fried’s Frailty phenotypic criteria

or their modifications were used in most studies.

In US, several recent and older community based studies in elderly

population >65 years of age in men and women, depict the prevalence of

frailty to range from 4 to 26% and the prevalence increases with increase

in age i.e., 3 to 7% aged 65-75 years, 20 to 26% >80 years and 1/3 of 90

years are frail(42)(2).

In the SHARE study(43) (the largest survey performed in Europe

and Israel, covering 10 European countries and Israel) the overall

prevalence of Frailty was determined to be 17% ranging from 5.8% in

Switzerland to 27.3% in Spain. The prevalence of Pre-frailty was higher

in Germany (34.6%) and Spain (50.9%).

Prevalence varies according to sex (more in women as women’s

life expectancy is more than men and tends to live longer than men and so

the frailty status is common in elderly women), ethnicity (higher in

27

Hispanic and African Americans), socioeconomic status (poor education

and poverty are closely associated with frailty)(44).

INDIAN EPIDEMIOLOGY

Only few studies are available to show the prevalence of frailty in

India. The level of frailty was higher in the higher income countries than

the lower income countries which were evident in a study done across 14

countries of higher income status and 6 countries of lower income status

including India. The variability in prevalence between developed and

lower income countries was due to increased life expectancy in wealthier

countries where advanced health care system, social support increase the

longevity of life(86).

A hospital based study of 250 individuals showed the prevalence of

frailty to be 33%(88). Based on frailty Index, cumulative deficit model

comprising about 40 variables, a large population study conducted across

6 countries including India, the prevalence of frailty was found to be

55.5% in India(87).

FRAILTY AND AGING

The definition of Frailty (i.e., a state in which, Dysregulated

multiple system results in decline in functional reserves and increases the

vulnerability to stressors) has similarity to that of aging (i.e., a process in

28

which loss of molecular/ cellular functional properties results in

diminished adaptability responses to internal/external stress thereby an

augmented vulnerability to disease and mortality).

Failing homeostasis forms the basis of both. The failure in

homeodynamics in aging process is global whereas the failure of

homeodynamics circles around energy metabolism and neuromuscular

changes(45).

This is evident from the following schematic illustration and it

shows that chronological and biological ages are not synonymous.

Chart 2 Vulnerability of Frail elderly people to a sudden, change in

health status after a minor illness(12)

The blue line represents a fit elderly individual who, after a minor

stressor event such as an infection, has a small deterioration in function

and then returns to homoeostasis. The red line represents a frail elderly

29

individual who, after a similar stressor event, undergoes a larger

deterioration, which may manifest as functional dependency, and who

does not return to baseline homoeostasis. The two horizontal dashed lines

represent the homoeostasis level of functional abilities before the stressor

event.

Frailty is a synergistic, multifactorial, complex phenomenon in

which sarcopenia (or) melting of muscle mass is the central component

and initiator of a circle of frailty. Frailty is self perpetuating.The

development of Frailty results in a negative spiral which further leads to

greater frailty and risk of adverse outcomes like disability, etc.

chart3 pathway towards frailty, disability and death.(2)

Excessive loss of energy and reserves bends ‘‘successful’’ ageing

toward prefrail and frail status, which also can happen due to disease

alone. Green dotted lines depict potential reversibility, which

is more feasible in prefrailty, but is possible even in the disability stage.

The risk of frailty increases on reaching a critical mass of dysregulation

30

due to constellation of decrease in energy reserves. Frailty may also be

reversible to a point (green dotted lines) if appropriate steps of prevention

(Primary/ Secondary) are taken. If not intervened, a point of no return is

reached and irreversible disabilities will develop. This idea of continum

of frailty should be taken into account while planning for prevention and

treatment in later and end stage frailty.

Frailty is considered a biological syndrome of decreased

physiological reserve. To understand its casuality, the basic principles of

disease mechanism and pathophysiology must be considered.

31

BASIC FRAMEWORK OF FRAILTY(14)figure4

Genetic Factors Environmental Factors

Molecular (or) biological level

damage more than as expected in

aging

Physiological system affected and

dysregulated

Other factors

1. Poor nutrition

2. Sedentary life style

3. Sarcopenia and its risk factors

4. Neuroendocrine changes with

aging

5. Oxidative stress ↑ed free

radicals, ROS, ↓ed

Antioxidants.

6. ↑Inflammatory Phenomena

7. ↓Immune mechanism

Compromised network of

Homeostasis

Manifestation as Frailty

To be identified at this level and

therapeutic interventions to be

planned to prevent adverse

outcomes Failure of compensatory

mechanisms even in response to

minor stressful events

Clinically evident as ↓ed functional capacity frail status

Will develop adverse outcomes. Hospitalization → institutionalisation →

Disability → can progress upto death

Falls, fear of falling → Hip

Fracture

Depression

32

A large number of direct, indirect and interacting risk factors are

involved in its causation. Many factors thought to be influential, have yet

to be thoroughly studied and their pathways to be elucidated. The main

links in this process are discussed here.

CELLULAR RESPONSES TO STRESSORS(45)

The cellular responses to stressors involves

1) Apoptosis (by controlled cell death, removes damaged/ aberrant

cells).

2) Senescence (alters the phenotype and blocks further proliferation)

Repair (removes damaged proteins, lipids and organelles and recycles

constitutent parts). Dysregulation of these responses, can contribute to the

failure in homeodynamics seen in frailty.

1) Increased apoptosis → Tissue/ organ atrophy → Weakness

2) Expression of senescent cellular phenotype → Increased

proinflammatory cytokine release →Dysregulated inflammatory

state.

3) Deficits in repair in specific tissue (muscle, nervous, bone) →

Oxidative stress and further damage due to other products of

impaired repair response.

33

Oxidative Stress

Imbalance among reactive oxygen species, free radicals and

antioxidants lead to oxidative stress and this imbalance stimulate

apoptotic effects of TNF-α and they are thought to be associated with

aging and sarcopenia.

POOR NUTRITION

Poor appetite regulation in elderly and the deficient intake of

multiple nutrients like Vitamin B6, Vitamin B12, Vitamin C, Beta-

Carotene, Selenium, Vitamin E, and PUFA are all independent correlate

with frailty in several studies(46)(47).

Low levels of certain proteins like carnitine, mitochondrial CP-II,

ALT, nutritional markers like HDL Cholesterol, BNP correlate with

frailty(35).

Body composition:

1) Advancing age is linked with profound changes in body

composition and the most remarkable of which is sarcopenia, a

major cause of physical function decay, disability and mortality.

2) Frailty and sarcopenia resembles the problem of the egg and the

chicken.

34

3) It is unfortunate that a clear defining architecture to accommodate

and study the two conditions, sarcopenia and Frailty has yet to

come.

4) However the two would converge in near future because both

conditions deal with the common subclincal and clinical

manifestations of aging. From a practical view point sarcopenia

may be considered a chief component in the pathway of Road to

Frailty(48).

5) The term “Sarcopenia” is delineated as loss of muscle mass and

decline in muscle function which occurs with aging.

6) Operationally it is described as an appendicular lean body mass <2

S.D. below that of a young healthy population corrected for height

in meters squared(49)

The following are the changes occurring in muscular system with aging

� Lean body mass (composed of Muscle & Visceral organs)

decreases steadily from thirties and the % represented by muscle

decline rapidly in late life.

� Decrease in muscle mass due to atrophy of muscle fibres (Fast

twitch fibers>Slow twitch fibres) is probably because of

progressive loss of motor neurons.

� Fat and fibro connective tissue accumulates inside muscle and it

affects muscle quality and function.

35

Both decrease in muscle mass and decrease in muscle quality and

function leads to decrements in muscle strength and it contributes to

weakness and decreased functional capacity and loss of independence.

Diminished muscular strength is also a predictor of mortality

independently.

Many candidate mechanisms may lead to sarcopenia, some of

which are portrayed in figure No.5 and Table 4.

Figure 5 mechanisms of sarcopenia

36

Table 4 Risk factors of sarcopenia

Risk factors of sarcopenia

Factors Aging process Chronic health

conditions

constitutional

� female sex

� LBW

� genetic

susceptibility

lifestyle

� malnutrition

� low protein

intake

� smoking

� physical

inactivity

living conditions

� immobility

� starvation

� deconditioning

increased muscle turn over

� ↑protein degradation(catabolism)

� ↓protein synthesis(anabolism)

reduced number of muscle cells

� ↑myostatin

� ↑apoptosis

endocrine deregulation

� ↓testosterone,DHEA

� ↓oestrogen, ↓vit.D3

� ↑thyroid function

� ↓GH,IGF-1

� ↑Insulin resistance

Changes in neuromuscular system

� ↓ CNS input (loss of a-motor

neurons)

� Neuromuscular disjunction

↓CNTF, ↓motor unit firing

rate

Mitochondrial dysfunction

� ↓Peripheral vascular flow

� cognitive

impairment

� mood disturbances

� osteoarthritis

� chronic pain

� DM

� CCF

� Renal failure

� Liver failure

� Respiratory failure

� obesity

� catabolic effects of

drugs

� cancer?

� chronic

inflammatory

state?

Most sarcopenic individual have lost fat as well. However a subset

of individuals remain fat whicle losing muscle mass. These individuals

have been characterized as the “Sarcopenic obese” or the “Fat frail”.

37

“Myosteatosis”- the infiltration of fat into muscle appears to be a separate

condition related to insulin resistance. Longitudinally, those sarcopenic

obese individuals have been found to be the most likely to develop future

disability and mortality.

Other changes in Body composition(40)

Though the fat mass increases in middle age and declining in late

life, the visceral fat continues to accumulate and it increases the waist

circumference across life span.

Fibroconnective tissue also increases in multiple organ systems. In

bony tissue, bone strength is decreased due to progressive

demineralization and modification of bony architecture and so the

fracture risk is augmented. Due to influence of gonadal hormones and

peak bone mass, there are sex differences in bony strength.

HORMONAL CHANGES(50)

Via the hypothalamus- Pituitary axis, the neural system and the

endocrine system are linked and through the signaling action of a series

of homeostatic hormones they control the metabolism and energy

utilization.

The 3 main endocrine changes occurring with aging which are

presumed to be in the causative pathway of Frailty are

38

1) ↓in GH levels → ↓ in IGF-1 production by liver.

2) ↓in Estrogen and Testosterone → ↑ release of LH & FSH

3) ↑ in Cortisol Secretion + ↓ in DHEA production

Other proposed hormonal changes implicated in the genesis of

Frailty are all in its infancy level.

Figure 6Hormones and frailty

T _ testosterone; E _ estrogen; GH _ growth hormone; IGF-1 _

insulin growth factor 1; DHEA _ dehydroepiandrosterone; Vit D _

vitamin D.

39

Inflammaging and immune system alterations in frailty(51).

Figure 7 inflammatory and immunologic changes and frailty

40

Metabolic Causes of Frailty(49)

Figure 8 Metabolic Causes of Frailty

41

Other risk factors for fraility(49)

Figure 9 Other risk factors for fraility

FRAILITY AND DISABILITY

The terms disability, co-morbidity were considered synonymous

previously. Now they should be regarded as separate clinical entity

although interrelated.

Disability is considered as difficulty or dependency in carrying out

activities essential to living independently. It can be caused by a disease

42

or several disease in combination. The two key factors which differential

frailty from disability are

1) Disabilty can result from dysfunction of single or multiple systems.

Whereas frailty is always due to multisystem contributions.

2) Disability is not necessarily associated with instability whereas for

frailty, instability is intrinsic.

Frailty is not the stage prior to disability, rather it predisposes to

stage of disability. Disability can follow from a previous stage of

robustness or from the stage of frailty or from the previous state of

dependency which is deteriorating(35).

Similarly frailty can head away to disability or recover to previous

level of functional status or be maintained.

FRAILTY AND COMORBIDITIES

Not all older adults with co-morbid diseases are frail. Also not all

frail elderly people have multiple co-morbid diseases. This is evident

from CHS in which 67.7% frail elderly had multimorbidity among the 9

diseases considered. However only 9.7% of older adults with

multimorbidity were frail. It suggests that frailty may be caused either

by mechanisms other than that for chronic diseases or by the mechanisms

43

involved in chronic diseases which have reached a severe or advanced

state(52).

Frailty Trajectory(53)

Figure 10 frailty trajectory

IDENTIFICATION OF FRAILTY STATUS

To avoid the development of disability, frailty status has to be

identified in its earlier course to implement strategies for prevention and

treatment in early stages.

44

USE OF BIOMARKERS(2)

A biomarker is defined as “A characteristic that is objectively

measured and evaluated as an indicator of normal biological process,

pathogenic process or pharmacologic responses to a therapeutic

intervention”.

Functional, biological (laboratory variables), imaging, related

parameters may be considered as biomarkers.

Some of the currently proposed biomarkers are

1) Physical performance and muscle strength measures (Gait speed

and Grip strength).

2) Body composition measures (Appendicular mass and

anthropometry values).

3) Inflammatory markers (IL-6 and CRP).

4) Antioxidants and oxidative markers.

5) Nutritional parameters (Albumin, Hb, urinary creatinine)

6) Hormonal Levels (GH, IGF-1, Testosterone, DHEA) and much

more.

However none are good biomarkers for detecting frailty. Their use

is currently restricted to research.

45

SCREENING TOOLS FOR FRAILTY

There are several instrumental tools to screen for frailty. Most of

the screening tools assess physical functioning gait speed and cognition.

The most commonly cited, screening is Fried’s Frailty phenotype.

It was developed on the basis of observation of progressive weakness and

declines in activity in older adults most vulnerable to adverse outcomes

and has been validated in the cardiovascular health study (CHS)

involving over 5000 men and women age >65 years.

Other tools which are used to screen frailty are

1) Single item surrogate assessments of frailty include TUG and Hand

grip strength.

2) SPPB(54)(It includes balance test , chair stand test and 5 m gait

speed test).

3) FRAIL Scale(55)

Fatigue (“are you fatigued?”)

Resistance (“can you climb one flight of stairs”)

Ambulation (“can you walk one block?”)

I llness (greater than five)

Loss of weight (greater than 5 percent)

46

“Yes” to three or more questions indicates frailty. “Yes” to

one or two questions indicates pre-frailty.

4) SOF Frailty Tool(56) (Annexure d))

Frailty is defined as the presence of atleast two of three

components:

• Weight loss of 5 percent in last year

• Inability to rise from a chair five times without use of arms

• A “No” response to the questions “ do you feel full of

energy”

5) PRISMA questionnaire(57) (Annexure e))

6) Clinical Fraility Scale(58) (Annexure f))

It is a rapid frailty screening tool that is scored between 1(very fit)

and 7(severely frail) based on self report of co-morbidities and the

need for help with activities of daily living(ADLs)

7) BGS Guidelines(59)

• It recommends assessment of the elderly for presence of

frailty at all encounters with health care workers. It includes

Gait speed , the Timed-Up and- Go test and the PRISMA

questionnaire.

• Edmonton frail scale is recommended for elective surgery.

8) Rockwood Frailty Index

The deficit accumulation or index approach to measue frailty is

based on the accumulation of illnesses, functional and cognitive

declines and social situations that are added together to calculate

47

frailty. It requires 20 or more medical and functional –related

questions. The higher the number of deficits , the higher the frailty

score.

9) Edmonton Frail Scale(60) (Annexure g))

PREVENTION AND MANAGEMENT

Frailty is often identified at the end stage when there is clinically

evident history of recurrent falls and injuries, disability, recurrent hospital

visits due to acute illness, poor recovery from acute stress. Due to risk of

high morbidity & mortality secondary to frailty, it is imperative to

recognise them at an earlier stage & strategies for intervention to be

implemented even at the prefrail stage to give healthy quality of life to

older individuals who are at risk of adverse outcomes. To date, curative

treatments for frailty are unavailable.

However the currently available evidences suggest that the

modalities available can improve clinical outcomes in this patient

population and thereby it’s possible to prevent disability and frail status

can even be reverted back to the stage of prefrailty due to its dynamic

nature. Though there is no universal consensus definition & assessment

tools for frailty, the ultimate aim is to prevent the at risk individuals from

adverse outcomes. Most management strategies concern to improve the

muscle mass, strength and energy. The proposed models in medical care

48

for elderly(61) are 1) GEM (geriatric evaluation and management) in

which direct care & follow up care is given by the interdisciplinary team,

2) CGA (comprehensive geriatric interdisciplinary assessment and

treatment) in which the consultative interdisciplinary team makes specific

recommendations to the patient’s primary care provider, 3) PACE

(Program for All inclusive Care for the Elderly) and 4) acute care for

elderly(35).

Following are the approaches which can be incorporated in clinical

practice for prevention & management of frailty.

1) To find at risk individuals in routine practice & for effective

clinical care an extensive CGA /an interdisciplinary assessment &

management is needed.

2) Identify secondary frailty from latent undertreated or end stage

disease, other catabolic states

3) Screen for factors which exacerbate vulnerability to stressors-

polypharmacy, hospitalisation, surgery or other stressors.

4) Establish patient centered goals and advise regular follow up

with geriatric interdisciplinary management team.

5) To institute preventive measures for primary frailty once

secondary frailty is ruled out.

49

PRIMARY PREVENTION (2):

It is vital to prevent the triggers. Primary prevention with probable

potential to prevent or postpone frailty focus mainly on lifestyle issues

and they are regular physical activity, vascular healthy diet , avoiding

smoking, weight control, proper nutrition, moderation with alcohol.

Recent evidences suggest drugs targeting RAA system affect body

composition & prevent sarcopenia. Drugs with potential side effects like

statins causing myopathy which probably limits the physical activity can

be avoided.

SECONDARY PREVENTION :

Aims to improve the prognosis and prevent or postpone the

development of disability and other adverse outcomes from frail status.

The therapeutic targets for frailty which are under investigation(35) are

1) Antioxidants (vit C, allopurinol)

2) Hormonal supplements (testosterone, DHEA, GH, vit D)

3) Behavioural interventions (calorie restriction & ↑ physical

activity)

4) Drugs like acetaminophen, anti myostatinAb, ACEIs

5) Genetic manipulation

6) Targeting inflammation with antirheumatic drugs.

50

Good numbers of evidence are there which show Resistance

training Exercise with proper nutrition can increase the strength in a frail

as well as non-frail group(62). Earliest the patient can start, better will be

the response. Though there are areas which need investigation, it is highly

recommended for elderly frail individuals to have regular physical

activity and exercise, especially Resistance training exercise rather than

aerobic exercise to modify frailty & its adverse outcomes.

THYROID GLAND –ANATOMIC CONSIDERATIONS

Thyroid gland one among the largest endocrine glands weighs

about 15-20 grams. It is situated in the anterior portion of neck, below

and lateral to the thyroid cartilages. It consists of 2 lateral lobes with an

isthmus which connects the two lateral lobes, and sometimes a pyramidal

lobe. Embryologically, it arises from a small tissue at the base of tongue,

which later descends down as the thyroglossal duct and occupies the

anterior portion of neck between larynx and trachea. Multiple spherical

follicles (acini) lined by polarised epithelial cells, that surround secreted

colloid is responsible for the production of thyroid hormones(63).

51

THYROID HORMONES FORMATION & SECRETION (64)

Figure 11 THYROID HORMONES FORMATION & SECRETION

THYROID HORMONES STRUCTURE (63)

Figure 12THYROID HORMONES STRUCTURE

52

REGULATION OF THYROID HORMONE SECRETION (65)

Figure 13 REGULATION OF THYROID HORMONE SECRETION

Hypothalamus secretes TRH which stimulates anterior pituitary to

produce TSH which in turn stimulates thyroid gland to synthesize T4 &

T3 from dietary iodides and follicular thyroglobulin, and are released in

to circulation. Both T3 & T4 in turn has both direct & indirect negative

feedback effect on secretion of TSH by action on anterior pituitary &

hypothalamus separately.

TRANSPORT OF THYROID HORMONES

Both T3 & T4 will bind with plasma proteins mainly with TBG

(Thyroxine – binding globulin), less withTransthyretin (TTR) and

albumin and they are released slowly to tissue cells. T4 is deiodinated

53

peripherally (Liver, Muscle, kidney & other tissues) by Deiodinase

enzymes (Type I, II, III) to T3 .About 85% of T3 is derived from T4 to

T3 conversion. The direct production from thyroid constitutes only 15%.

More over T3 is less protein bound than T4 and has quick onset of action.

Also T3 has high affinity to Thyroid hormone receptors. Reverse T3, a

biologically inactive form is also derived from deiodination of T4 inner

tyrosyl ring rather than at outer phenolic ring.

MECHANISM OF ACTION OF THYROID HORMONES (66)

There are specific thyroid hormone response elements (TRE) on

the DNA at which the thyroid hormone receptor forms a heterodimer with

RXR (Retinoid X receptor) TR-RXR. T4 exerts its action by converting

into T3. In the absence of T3 binding to TR, TR-RXR heterodimer

bounded with TRE, recruits COR – Co-repressor & results in gene

silencing. When T3 binds with TR, it disrupts CoR binding with the

heterodimer & it promotes binding of CoA (Co-activator) & increase

mRNA expression leading to formation of new proteins.

54

Figure 14 thyroid hormone action

PHYSIOLOGIC ACTIONS OF THYROID HORMONE (67):

At Cellular level

Thyroid hormones act at cellular level to increase size and number

of mitochondria and the total membrane surface area of mitochondria

increases directly proportional to the increased metabolic rate of the

whole individual. They also increase Na+ K+ ATPase activity, which in

turn causes increase in transport of Na+ & K+ ions across cell

membranes. This process uses energy and it increases the heat production

in the body. Also they activate the sodium pump & further increases heat

production. However the increase in number and activity of mitochondria

could be the result of increased activity of the cells. Also uncoupling of

oxidative phosphorylation is stimulated(64).

On Growth: the effect of thyroid hormone on growth is evident by

the growth retardation seen with lack of thyroxine in growing children. In

55

excess, it increases growth and makes the child appear taller at an earlier

age. However the eventual height of the adult is shortened due to

hastened bony maturity and early closure of epiphyses(67).

On metabolism: Basal metabolic rate� ↑ to 60-100% above

normal in case of thyroid hormone excess.

Table 5 thyroid hormones action on metabolism

Carbohydrate

metabolism Fat metabolism

Protein

metabolism Vitamins

↑ peripheral

glucose uptake

↑glycolysis

↑gluconeogenesis

↑insulin secretion

by secondary

effect

↑glycogenolysis.

All these effects

are attributed to

↑edcellular

metabolic

enzymes.

↑ lipolysis and

mobilization of lipids

from adipose tissue

↑ FFA level in plasma

and its oxidation by the

cells

↓ cholesterol, TGL ,

phospholipids levels in

plasma

↑expression of LDL

receptors on liver

resulting in ↑ hepatic

removal of cholesterol

from circulation.

↑ transcription

and translation

in protein

synthesis

↑ Catabolism

of proteins.

↑ Vitamin

requirements as

vitamins are

essential for

many bodily

enzymes, co-

enzymes which

are increased

with actions of

TH.

On Body Weight: ↓body weight & its deficiency causes weight gain

On Cardiovascular System:

56

(↑ Heart rate, ↑force of contraction, ↑cardiac output) → ↑systolic BP.

Vasodilation due to metabolites produced due to increased

metabolic activities and so decrease in diastolic BP. Pulse pressure

increased and MAP maintained(67).

On Respiration:

↑ O2 utilization, ↑ CO2 formation and so there is ↑ in rate and depth of

respiration(67).

On Gastrointestinal Tract:

↑ Appetite, ↑food intake, ↑ secretion of digestive juices, ↑gut motility

Can cause diarrhoea in hyperthyroidism and constipation in

hyperthyroidism(67).

On Central Nervous System:

TH is essential for the development of nervous system in foetal &

post natal period.

Also they stimulate CNS. Hypersecretion causes anxiety

complexes, extreme nervousness, tremors, paranoid thoughts.

Hyposecretion leads to lethargy, somnolence (excess sleep)(67).

On Skeletal Muscle:

57

Slight increase in TH makes them to react with vigor, still more

hypersecretion causes muscle weakness due to protein catabolism

whereas hyposecretion makes the muscles sluggish and they relax slowly

after a contraction(67).

On Sleep:

Due to thyroid hormones’ exhaustive effect on muscular and

central nervous system, the individual feels tired constantly. But they

can’t sleep due to its action on synapses. Hyposecretion leads to

somnolence(67).

On Sexual Function:

Hyposecretion results in ↓ sexual drive, whereas hypersecretion↓

the potency. Both hypo and hypersecretion causes menstrual

irregularities(67).

On Other Endocrine glands:

Increases the demand for secretion by other endocrine glands(67).

58

Aging Changes of Thyroid Gland(1):

Table 6 Aging Changes of Thyroid Gland

Anatomical changes of thyroid

gland with aging :

Changes in hypothalamo-

pituitary-thyroid axis with

aging:

The anatomical changes of thyroid

gland with aging are controversial.

• There may be reduction or

increase in size and weight

of the gland or no change.

• Nodularity is increased.

• It undergoes atrophy,

fibrosis or lymphocytic

infiltration.

Pituitary TSH response to TRH

↑↔↓

TSH concentration ↑↔↓

↓↓ diurnal variation of TSH

↔ thyroid gland response to TSH

↓ thyroid iodide clearance

↓ renal iodide clearance

↔serum TBG concentration

↓total T4 production

↓ T4 degradation

↓ conversion of T4 to T3

↔ serum T4 concentration

↔↓ serum T3 concentration

Hormonal changes in thyroid dysfunction:

Table 4 Hormonal changes in thyroid dysfunction

Thyroid dysfunction TSH fT3, fT4

Hyperthyroidism Undetectable/decreased Increased

Subclinical

hyperthyroidism Undetectable/decreased Normal

Hypothyroidism Increased Decreased

Subclinical

hypothyroidism Increased Normal

59

Prevalence of thyroid dysfunction in elderly:

In the Framingham heart study, 5.9% of women and 2.3% of men

aged >60 years had TSH values >10 µIU/L. 39% of whom had subnormal

free T4 levels. In elderly women, the prevalence of subclinical

hypothyroidism is upto 20% whereas in elderly men it is upto 8%(68).

The NHANES III study(69) showed that 0.7% of all individuals had a

serum TSH level <0.1 µIU/L and 1.8% had serum TSH levels below the

lower limit of reference range of 0.4 µIU/L. The prevalence of

hypothyroidism in elderly ranges from 0.5 to 3%. In elderly the classic

symptoms of thyroid dysfunction are often overlooked or misdiagnosed

as the symptoms are attributed to normal aging or confused with co-

existing illness.

Conceptual Map(70–75)

Skeletal muscle is the principal target for thyroid hormones.The

bioenergetics state depends on balance between energy production and

energy utilization i.e., between ATP production and its hydrolysis.

Thyroid hormones play vital role in myosin heavy chain

composition (DNA expression of myosins), Ca-ATPase and Na-K pump

isoforms, and has effects on protein metabolism, myofibrillar and calcium

regulatory proteins and energy metabolism (influences the activity of key

enzyme of main energetic pathways, Glycolysis & mitochondrial

60

metabolism). Moreover Oxidative phosphorylation is inefficient in

thyrotoxic skeletal muscle because of an increase in uncoupling of

oxidative phosphorylation. Thus thyroid hormones modulate the energetic

balance in muscle by modifying energy production and energy

consumption due to increased protein catabolism. Muscle weakness

occurs in thyroid hypersecretory states (Thyrotoxic myopathy).

Hypothyroidism is also associated with muscle weakness, cramps and

stiffness.

From these clinical presentations, it is evident that muscle

weakness & fatigue are common to both hypothyroidism and

hyperthyroidism in humans. This implies that thyroid disorders are

associated with decreased skeletal muscle mass and strength, a major

determinant of frailty and disability in order individuals. Chronic

inflammation & concomitant down regulation of multiple endocrine

factors characterize frailty suggesting that endocrine factors could be

useful for early identification of frailty which is a state at risk for adverse

outcomes. Also when compared to young, the prevalence of subclinical

thyroid dysfunction is high in elderly and overt symptoms of hypo/hyper

thyroidism are less likely to be recognized in elderly people with

subclinical thyroid dysfunction and the diagnosis is often overlooked.

Furthermore small differences in thyroid function in euthyroid subjects

has been associated with different clinical parameters, Metabolic

61

syndrome, Atrial fibrillation, cardiovascular mortality, risk of fracture.

Moreover, subclinical thyroid dysfunction has also been associated with

decreased functional capacity, mobility & neuromuscular abnormalities

(70–75).

A study states that low normal fT4 levels in elderly people has

survival benefit i.e.,it improves longevity(76–78). However the limited

data available evaluated the association of thyroid dysfunction (or

differences in thyroid functions between euthyroid subjects) to frailty in

elderly which in turn is a road to risk for adverse outcomes. Hence,

identification of differences in thyroid function in euthyroid elderly

subjects as a risk factor for frailty would improve understanding of

endocrine pathophysiology and will give us the chance to distinguish

elderly people at risk for poorer health outcomes.

62

Table 5 Summary of studies on thyroid abnormalities and frailty.

Summary of studies on thyroid abnormalities and frailty.

Study Design N , age Frailty index Main findings

Wang et al,

2010(79)

Cross

sectional 641 women

Cardiovascular

Health Study

index

Community-dwelling

older women

with positive TgAbs and

TPOAbs

were found less likely to

be frail than

seronegative women

Yeap et al,

2012(80)

Cross

sectional

3943 men

70-89 years FRAIL scale

High-normal FT4 level

was

independently associated

with

frailty among ageing men

Virgini et

al,

2015(81)

Prospectiv

e

Cohort

1455 men

>65 years

Cardiovascular

Health Study

Index

Subclinical

hyperthyroidism, but not

subclinical

hypothyroidism, was

found associated with

increased odds

of prevalent but not

incident frailty

Veronese et

al, 2016(82)

Prospectiv

e

Cohort

2571 (cross-

sectional)

1732

(longitudinal)

>65 years

Fried’s index

Highest TSH quintile in

men and

lowest TSH quintile in

women were

associated with frailty in

both cross-sectional

and longitudinal analysis

MATERIALS AND METHODS

63

MATERIALS AND METHODS

STUDY CENTRE : Geriatric Medicine OPD & ward (Male &

Female),

Rajiv Gandhi Government General Hospital, Chennai-3.

ETHICAL COMMITTEE

APPROVAL : Approved by the Institutional Ethical

Committee of

Madras Medical College, Chennai

STUDY DESIGN : Cross sectional study (hospital based)

PERIOD OF STUDY : 6 months (February 2017- July 2017)

SAMPLE SIZE : 200 patients

INCLUSION CRITERIA :

Persons aged above 60 years willing to consent for the study

EXCLUSION CRITERIA :

• Persons aged above 60 years not willing to consent for the study.

• Critically ill patients like advanced cardiac failure, stage 4,5

CKD.

• Acute stroke, previous stroke with major residual deficits

• Parkinson’s disease, dementia, bed ridden – immobile patients, H/o hip replacement

• Known hypothyroidism patient on thyroxine supplementation

64

• Known hyperthyroidism patient on antithyroid drugs.

• H/o medications like beta blockers, amiodarone, lithium

• H/o radiation in the past, thyroid surgeries.

• H/o malignancies.

DETAILS OF THE STUDY:

As per the above mentioned inclusion and exclusion criteria,

People aged above 60 years coming to geriatrics department, Rajiv

Gandhi Govt. General Hospital, Chennai were selected by Simple random

sampling. After getting informed written consent from all the study

participants, their literacy level, contact information were collected. Then

clinical history of selected conditions like Hypertension, Diabetes

Mellitus, Dyslipidemia, COPD, bronchial asthma, old CAD, old CVA,

Fall history were obtained. Their habitual history like smoking and

alcohol intake were obtained. Anthropometric evaluation by measuring

height, weight and calculating BMI is done. After the baseline evaluation,

Fried’s frailty phenotypic criteria was employed to assess the frailty

phenotype and it comprises of the following five components. They are

1) Shrinking/Weight loss

2) Exhaustion/poor endurance

3) Weakness

4) Slowness

65

5) Low physical activity levels

After assessment by Fried’s Frailty phenotype criteria , the study

participants were categorized into 3 groups based on the number of

components they had.

Those with ≥ 3 components were categorized as frail and those with 1-2

components as prefrail and those with none of them as non frail. Then

venous blood samples were collected from study participants of each

group for estimation of ft3 , fT4 and TSH levels by CLIA(Chemi

Luminescent ImmunoAssay) method. Then the raw data was tabulated

and analysed statistically.

Table 6 Criteria Used to define Frailty

Criteria Used to define Frailty Using a modified version of the

construct described by Fried et al

Components of

Frailty Phenotype

Assessment measures

Shrinking/Weight

loss(self reported)

Self reported unintentional weight loss of ≥5kg (not

due to dieting or exercise) in prior 12 months or

unintentional weight loss ofatleast 5% of previous

year’s body weight

Exhaustion/poor

endurance(self

Using the CES (Center for Epidemiologic Studies)-

Depression Scale, the following two statements are

66

reported) read or explained. “I felt that everything I did was an

effort in the last week“ , “I could not get going in the

last week”. The question is asked “how often in the

last week did you feel this way?”

0 = rarely or none of the time (<1day),

1 = some or a little of the time (1-2 days),

2 = a moderate amount of the time (3-4days) or

3 = most of the time.

Subjects answering “2” or “3” to either of these

questions are categorised as frail by the exhaustion

criterion

Low physical

activity levels

Scored by Physical Activity Scale for the Elderly

(PASE) ; cut off points : Men <64 , Women <52

(Rothman et al., 2008) will be used for determining

frailty by low physical activity criterion.

67

Components of

Frailty

Phenotype

Assessment measures

Slownessi.e.,low

gait speed

Time in seconds to complete a 4m/15 ft walk at usual

pace. Gender and height specific cut off points

provided by Fried et al (2001) for frailty will be used

Cut off for time to walk 15 feet

criterion for frailty

MEN

Height ≤ 173 cm ≥ 7 seconds

Height > 173 cm ≥ 6 seconds

WOMEN

Height ≤ 159 cm ≥ 7 seconds

Height > 159 cm ≥ 6 seconds

Weaknessi.e.,

low hand grip

strength

Low hand grip strength measured by Hand Held

Dynamometer.

Gender and BMI specific cut off points provided by

Fried et al (2001) for frailty will be used

Cut off for grip strength (kg)

criterion for frailty

MEN

BMI ≤24 ≤ 29

BMI 24.1-26 ≤ 30

BMI 26.1-28 ≤ 30

BMI >28 ≤ 32

WOMEN

BMI ≤23 ≤ 17

68

BMI23.1-26 ≤ 17.3

BMI 26.1-29 ≤ 18

BMI >29 ≤ 21

HAND GRIP STRENGTH

Hand Grip Strength was assessed using a hand dynamometer with

participant’s arm by their sides and elbow in right angle . They were

instructed to rest in a chair with arm support to rule out gravitational

force. They were asked to press the dynamometer for 3 times in each

hand and maximum of these values was taken as the hand grip strength.

69

Figure 15 hand grip dynamometer

70

Low Physical Activity assessed by PASE Scoring(83)

Table 7 PASE Scoring

71

STATISTICAL ANALYSIS

Descriptive statistics (median & interquartile range) were calculated for

each variable.

The F statistic test was applied to assess the statistical significance of the

relationship between frailty categories and fT4, fT3, TSH levels.

Pearson correlation test was used to find correlation between continuous

variables and fT4, fT3, TSH levels.

The potential that either an observed association or lack of association

between frailty and fT4, fT3, TSH levels could be due to confounding by

other subject characteristics was evaluated. The Pearson χ2 test was

applied to investigate relationships between frailty and these other

characteristics age (60–69, 70–79, ≥80), gender (male, female) and body

mass index ( ≤ 18.5, 18.5-24.9,25-29.9,≥ 30).

Pearson correlation was also used to find correlation between fT3, fT4,

TSH levels.

All the analyses were performed using SPSS software package version

21.

A 5% threshold was used for declaring a statistical significance in all tests.

RESULTS

72

RESULTS Table 8 age distribution in total

Age distribution

Age Group Frequency Percent

60-69(young old) 138 69.0

70-79(old old) 48 24.0

>=80(very old) 14 7.0

Total 200 100.0

73

chart 4 age distribution in total

Of the 200 subjects studied , 69%(n=138) are in the age group of 60-69

,24%(n=48) are in the age group of 70-79, only 7%(n=14) are the

oldest(very) old. This 7% can be due to either under-reporting to hospital

or they might have died.

74

Gender distribution in Total

chart 5 sex distribution in total

Table 9 Sex distribution in total

Sex distribution

Gender Frequency Percent

Male 98 49.0

Female 102 51.0

Total 200 100.0

Among the 200 who participated in this study, 102(51%) are females

aged more than 60, 98(49%) are males aged above 60.More or less equal

number of participants from both gender have took part in this study.

75

Frequency distribution of Frailty Phenotype Categories

chart 6 Frequency distribution of Frailty Phenotype Categories

Table 10 Frequency distribution of Frailty Phenotype Categories

Frequency distribution of Frailty Phenotype Categories

FRAILTY

CATEGORY

Frequency Percent

Non Frail 42 21.0

Pre Frail 86 43.0

Frail 72 36.0

Total 200 100.0

In this hospital based study in a tertiary care centre, of the 200 subjects

studied, the prevalence of frailty is found to be 36 % (n=72). The

prevalence of elderly people who are non frail and pre frail are 21%

(n=42) and 43%(n=86) respectively. This indicates the prevalence of

frailty is more in hospitalised elderly than community dwelling elders,

where the prevalence ranges from 4% to 33%.

76

Prevalence of individual components of frailty phenotype criteria

chart 7 Prevalence of individual components of frailty phenotype criteria

Table 11 Prevalence of individual components of frailty phenotype criteria

Prevalence of individual components of frailty phenotype criteria

Components of frailty phenotype Frequency Percent

WEIGHT LOSS 27 13.5%

WEAKNESS 131 65.5%

SLOWNESS 127 63.5%

EXHAUSTION 59 29.5%

LOW PHYSICAL ACTIVITY 82 41.0%

65.5%(n=131) of the subjects studied has poor hand grip , 63.5%(n=127)

of the subjects in this study takes longer duration to complete distance of

about 15 ft. 41%(n=82) of the total study participants has less than

77

normal physical activity. 29.5% (n=59) of people in this study feel

exhausted for most of the days in a week. Only 13.5% (n=27) reported

weight loss in the past year.

Frequency distribution of individual components of frailty phenotype

Chart8 Frequency distribution of individual components of frailty phenotype

Table 12 Frequency distribution of individual components of frailty phenotype

Frequency distribution of individual components of frailty phenotype Frequency distribution of individual components of frailty phenotype N % within FRAILTY CATEGORY Non Frail (N=42)

WEIGHT LOSS 0 0.0% WEAKNESS 0 0.0% SLOWNESS 0 0.0% EXHAUSTION 0 0.0% LOW PHYSICAL ACTIVITY

0 0.0%

Pre Frail (N=86)

WEIGHT LOSS 5 5.8% WEAKNESS 63 73.3% SLOWNESS 59 68.6% EXHAUSTION 6 7.0% LOW PHYSICAL 25 29.1%

78

ACTIVITY Frail (N=72)

WEIGHT LOSS 22 30.6% WEAKNESS 68 94.4% SLOWNESS 68 94.4% EXHAUSTION 53 73.6% LOW PHYSICAL ACTIVITY

57 79.2%

79.2% (n=57) of frail people are reported to have low physical activity

when compared to prefrail group 29.1% (n=25). Frail elderly people

30.6% (n=22) experience weight loss more than the prefrail people 5.8%

(n=5). Almost 94% of frail group has low grip strength (n=68) and poor

gait speed (n=68) whereas it is 73.3% (n=63) and 68.6% (n=59) in the pre

frail group respectively.73.6% of frail group(n=53) are exhausted

whereas only 7% of the prefrail group(n=6) reported exhaustion.

Frequency distribution of no. of components of frailty phenotype

chart 9 Frequency distribution no. of components of frailty phenotype

79

Table 13 Frequency distribution of no. of components of frailty phenotype

Frequency distribution of no. of components of frailty phenotype

Frequency Percent

Number of

components

.0 42 21.0

1.0 13 6.5

2.0 73 36.5

3.0 28 14.0

4.0 37 18.5

5.0 7 3.5

Total 200 100.0

Of the total 200 subjects, only 3.5% subjects(n=7) are found to have all

the 5 components of frailty phenotype. 37(18.5%) among the 72 frail

elders have 4 among the 5 components.14%(n=28) of 200 participants are

found to have 3 components of frailty. Among the pre frail group ,

36.5% in total (n=73) are found having 2 components of

frailty.21%(n=42) of the study participants have none of the 5

components.6.5%(n=13) have only a single component

Table 14 Total Descriptives of other characteristics of the study sample

Total Descriptives of other characteristics of the study sample

N(%) Median

(interquartile range)

Weight loss 27(13.5%) 2.8(1-5)

Weakness 131(65.5%) 18.8(11.88-28)

Slowness 127(63.5%) 9.8(6.53-12.08)

80

Exhaustion 59(29.5%) 2(2-3)

Low physical activity 82(41.0%) 66.5(33.6-103.18)

THYROID FUNCTION

CATEGORY

Hypothyroidism 1(0.5%)

subclinical hypothyroidism 14(7%)

Euthyroid 184(92%)

subclincal hyperthyroidism 1(0.5%)

THYROID FUNCTION TEST

fT4 1.04(0.92-1.23)

fT3 3(2.6-3.9)

TSH 2.43(1.31-3.97)

Among the subjects studied 92%(n=184) are euthyroid , 7%(n=14) have

subclinical hypothyroidism, 0.5% (n=1)have subclinical hyperthyroidism,

0.5%(n=1) have hypothyroidism. The median thyroxine level in total is

1.04(0.92-1.23).The median TSH level is 2.43(1.31-3.97) and the median

fT3 level is 3(2.6-3.9). The median hand grip strength is 18.8 kg(11.88-

28).The median PASE score is 66.5(33.6-103.18).The median time to

complete 15 ft distance is 9.8(6.53-12.08).

81

Median age of study groups

chart10 Median age of study groups

Table 15 Median age of study groups

Median age of study groups Non

frail Pre frail

Frail total Significance

Median 66 64 67 66 Chi-square 8.299 P value 0.016 Interquartile

range (63-69)

(60-70)

(65-73)

(62-70)

The median age for frail people is 67(65-73) which is higher than the

other two groups and the 75th percentile age is 73 in frail which is also

higher than the other two group. Also age difference among these three

groups is statistically significant(p=0.016) when compared to other

groups on one way ANOVA analysis

82

AGE DISTRIBUTION AMONG THE STUDY GROUPS

chart 11 AGE DISTRIBUTION AMONG THE STUDY GROUPS

Table 16 AGE DISTRIBUTION AMONG THE STUDY GROUPS

AGE DISTRIBUTION AMONG THE STUDY GROUPS

AGE DISTRIBUTION

AMONG THE STUDY

GROUPS

FRAILTY CATEGORY Total

Pearso

n Chi-

Square

=21.48

9*

*p<0.0

01

Non

Frail

Pre Frail Frail

AGE

CATEGOR

Y

60-

69(young

old)

N 33 62 43 138

% 78.6% 72.1% 59.7% 69.0%

70-79(old

old)

N 9 12 27 48

% 21.4% 14.0% 37.5% 24.0%

>=80(very

old)

N 0 12 2 14

% 0.0% 14.0% 2.8% 7.0%

Total

N 42 86 72 200

% 100.0

% 100.0%

100.0

%

100.0

%

83

37.5%(n=27) of frail people fall within the age group of 70-79 yrs when

compared to prefrail group 14%(n=12) and robust 21.4%(n=9). This

indicates that prevalence of frailty increase with increase in age. Coming

to the oldest (very) old group it is observed that there is no non frail

participant, 14%(n=12) are prefrail and 2.8% are frail. This is indicating

that when frail elderly in 70s when crosses the age of 80 might either die

or underreport to hospital due to disability or other adverse outcomes and

p value(<0.001) is significant among these groups.

SEX DISTRIBUTION AMONG THE STUDY GROUPS chart 12 SEX DISTRIBUTION AMONG THE STUDY GROUPS

Table 17 SEX DISTRIBUTION AMONG THE STUDY GROUPS

SEX DISTRIBUTION AMONG THE STUDY GROUPS

SEX DISTRIBUTION

AMONG THE STUDY

GROUPS

FRAILTY CATEGORY Total Pearso

n Chi-

Square

=

1.578

Non Frail Pre Frail Frail

Gende

r male

N 24 39 35 98

% 57.1% 45.3% 48.6% 49.0%

84

femal

e

N 18 47 37 102 p=

0.454 % 42.9% 54.7% 51.4% 51.0%

Total

N 42 86 72 200

% 100.0% 100.0% 100.0

%

100.0

%

57.1%(n=24) of non frail ,45.3%(n=39) of prefrail and 48.6%(n=35) of

frail are males. 42.9%(n=18) of non frail, 54.7%(n=47)of pre frail,

51.4%(n=37) of frail are females. When comparing between male and

female there is a slight female predominance in pre-frail and frail group.

But the differences are not statistically significant.

Table 18Descriptives of baseline characteristics & their significance

Descriptives of baseline characteristics & their significance Baseline Characteristics

Non Frail

Pre-Frail

Frail Total Significance

Literacy

Pearson Chi-Square=18.604 * p= 0.02

illiterate N 12 28 29 69 % 28.6% 32.6% 40.3% 34.5% primary N 13 28 30 71 % 31.0% 32.6% 41.7% 35.5% middle school

N 6 9 3 18

% 14.3% 10.5% 4.2% 9.0% high school N 6 12 10 28 % 14.3% 14.0% 13.9% 14.0% graduate N 5 9 0 14 % 11.9% 10.5% 0.0% 7.0% Smoking Pearson Chi-

Square= 7.779 p= 0.100

never N 28 69 60 157 % 66.7% 80.2% 83.3% 78.5% past N 8 13 10 31 % 19.0% 15.1% 13.9% 15.5%

85

current N 6 4 2 12 % 14.3% 4.7% 2.8% 6.0% Alcoholism

Pearson Chi-Square=14.928** p= 0.006

never N 35 78 51 164 % 83.3% 90.7% 70.8% 82.0% past N 4 0 6 10 % 9.5% 0.0% 8.3% 5.0% current N 3 8 15 26 % 7.1% 9.3% 20.8% 13.0% >2 unintentional falls

N 2 2 7 11 Pearson Chi-Square=4.181 p= 0.124

% 4.8% 2.3% 9.7% 5.5% SHTN N 22 44 39 105 Pearson Chi-

Square=0.142 p= 0.931

% 52.4% 51.2% 54.2% 52.5%

Diabetes mellitus

N 24 35 31 90 Pearson Chi-Square= 3.255 p= 0.196 % 57.1% 40.7% 43.1% 45.0%

Dyslipidemia

N 11 9 2 22 Pearson Chi-Square=14.897** p= 0.001 % 26.2% 10.5% 2.8% 11.0%

COPD/BA N 10 11 20 41 Pearson Chi-Square=5.768 p= 0.056

% 23.8% 12.8% 27.8% 20.5%

MI/Angina N 11 14 9 34 Pearson Chi-Square=3.579 p= 0.167

% 26.2% 16.3% 12.5% 17.0%

CVA N 1 1 0 2 Pearson Chi-Square=1.559 p= 0.459

% 2.4% 1.2% 0.0% 1.0%

Most of the illiterate and primary educated were in pre frail and frail

category. Alcoholism and dyslipidemia history shows statistical

significance but the no of samples in each category is not adequate to

explain it.

86

Median BMI of study groups

chart 13 Median BMI of study groups

Table 19 Median BMI of study groups

Median BMI of study groups Non

frail Pre frail

Frail total Significance

Median 24.32 23.73 24.65 23.87 Chi-square 1.803 P value 0.406

Interquartile range

(21.76-26.42)

(20.74-26.51)

(21.56-27.75)

(21.60-26.99)

The median BMI is almost equal in all the groups. Also it doesn’t create

any statistical significance among these three groups

87

BMI DISTRIBUTION AMONG THE STUDY GROUPS

chart 14 BMI DISTRIBUTION AMONG THE STUDY GROUPS

BMI DISTRIBUTION AMONG THE STUDY GROUPS

BMI DISTRIBUTION

AMONG THE STUDY

GROUPS

FRAILTY CATEGORY Total

Pearson

Chi-

Square=

7.743

p=

0.258

Non frail Pre-frail Frail

BMI

category

<18.5

(underweight)

N 3 9 9 21

% 7.1% 10.5% 12.5% 10.5%

18.5-24.9

(normal)

N 25 45 29 99

% 59.5% 52.3% 40.3% 49.5%

25-29.9

(overweight)

N 13 21 25 59

% 31.0% 24.4% 34.7% 29.5%

>= (obese) N 1 11 9 21

% 2.4% 12.8% 12.5% 10.5%

Total N 42 86 72 200

% 100.0% 100.0% 100.0% 100.0%

88

34.7%(n=25) of frail elderly are overweight,and around 12% in both

prefrail(n=11) and frail(n=9) are obese. 9 each of pre-frail(10.5%) and

frail(12.5%) are underweight. But there is no significant difference

among these three groups with respect to BMI category.

Median hand grip of study groups

chart14 Median hand grip of study groups

Table 20 Median hand grip of study groups

Median hand grip of study groups Non Pre Frail total Significance

89

frail frail Median 29.66 17 13 18.8 Chi-square

55.601 P value 0.000

Interquartile range

(20.99-32.98)

(11.83-23)

(8.62-19.99)

(11.88-28)

Median hand grip in frail group 13(8.62-19.99) which is very much lesser

than non frail group 29.66(20.99-32.98) gives statistically significant

results.

90

Median 15 ft walking time of study groups

chart 16 Median 15 ft walking time of study groups

91

Table 21 Median 15 ft walking time of study groups

Median 15 ft walking time of study groups Non

frail Pre frail

Frail total Significance

Median 6.35 9.6 11.05 9.8 Chi-square 80.589 P value 0.000

Interquartile range

(6.10-6.7)

(6.4-12.0)

(10.00-13.6)

(6.53-12.08)

Median 15 ft walking time is less in non frail group than other groups.

The frail people takes more time to complete the 15 ft walking distance.

Median PASE score of study groups

chart 15 Median PASE score of study groups

92

Table 22 Median PASE score of study groups

Median PASE score of study groups Non

frail Pre frail

Frail Total Significance

Median 94.6 72.1 33.6 66.5 Chi-square 72.405 P value 0.000

Interquartile range

79.6-117.29

47.2-106.2

10.2-57.57

(33.6-103.18)

Median PASE score is higher in non-frail group 94.6(79.6-117.29) when

compared to other groups and it is much less in frail group 33.6(10.2-

57.57)

and is statistically significant.

Body mass index and thyroid function Table 23 Correlation between BMI and fT3,fT4& TSH

Correlation between BMI and fT3,fT4 & TSH

Free T4 Free T3 TSH

BMI(Kg/m^

2)

Pearson Correlation .107 .181* -.044

Sig. (2-tailed) .132 .010 .535

N 200 200 200

**. Correlation is significant at the 0.01 level (2-tailed).

*. Correlation is significant at the 0.05 level (2-tailed).

BMI is found to have positive correlation with fT3 with significance at

0.05 level(2-tailed)

93

Table 24 BMI category vs fT3,fT4 , TSH

BMI category vs fT3,fT4 , TSH

Free T4

p= 0.193

Free T3

P= 0.089

TSH

P= 0.399

Mean Median SD SEM Mean Median SD SEM Mean Median SD SEM

BMI category

<18.5 (underweight)

1.16 1.07 .35 .08 3.29 3.00 .95 .21 1.94 1.36 1.43 .31

18.5-24.9 (normal)

1.05 1.01 .23 .02 3.21 3.05 .79 .08 3.63 2.59 5.53 .56

25-29.9 (overweight)

1.12 1.08 .26 .03 3.25 2.90 1.04 .14 3.16 2.60 2.85 .37

≥30 (obese) 1.11 1.08 .20 .04 3.79 3.50 1.30 .28 2.81 1.90 2.22 .49

The mean fT4, fT3, TSH values respectively among underweight(1.16 ±

0.35,3.29 ± 0.95, 1.94 ± 1.36) group , normal weight group(1.05 ± 0.23 ,

3.21± 0.79,3.3 ±0.56 ), overweight group (1.12 ± 0.26,3.25 ± 1.04,3.16 ±

0.37) and obese group (1.11 ± 0.20, 3.79 ± 1.30, 2.81 ± 0.49) didn’t show

any statistical significance( p value 0.193, 0.089, 0.399)

Table 25 Frailty categories vsfT3 , fT4 , TSH

Frailty categories vs fT3 , fT4 , TSH f value

N Mean Std.

Deviation

Std.

Error

95%

Confidence

Interval for

Mean

Minimum Maximum

Lower

Bound

Upper

Bound

94

Free

T4

Non

frail 42 .8855 .12713 .01962 .8459 .9251 .64 1.30

67.081*

Pre

frail 86 1.0153 .13776 .01486 .9858 1.0449 .70 1.40

frail 72 1.2917 .27336 .03222 1.2274 1.3559 .57 1.74

Total 200 1.0876 .25307 .01789 1.0523 1.1228 .57 1.74

Free

T3

Non

frail 42 3.2550 .56064 .08651 3.0803 3.4297 1.93 4.20

0.204

Pre

frail 86 3.2588 .92129 .09935 3.0613 3.4564 1.70 6.40

frail 72 3.3479 1.16789 .13764 3.0735 3.6224 1.70 6.40

Total 200 3.2901 .95699 .06767 3.1567 3.4235 1.70 6.40

TSH

Non

frail 42 3.9588 .92773 .14315 3.6697 4.2479 1.73 5.45

2.785

Pre

frail 86 2.4141 2.04435 .22045 1.9758 2.8524 .50 16.25

frail 72 3.7701 6.67832 .78705 2.2008 5.3395 .12 50.77

Total 200 3.2267 4.28724 .30315 2.6288 3.8245 .12 50.77

Mean fT4 levels are lesser in non frail group (0.89±0.13) than

prefrail(1.02±0.14) and frail groups(1.29±0.27).Conversely , the mean

fT4 levels are high in frail group when compared to other two groups and

is statistically significant with f value 67.081 and p value <0.001.

Whereas for fT3 and TSH their mean values don’t show any significant

difference among non frail(3.256± 0.56 & 3.95±0.92) pre

frail(3.25±0.92&2.41± 2.04) , frail groups(3.34±1.16 &3.77±6.67)

95

Table 26 THYROID FUNCTION CATEGORY * FRAILTY CATEGORY

THYROID FUNCTION CATEGORY * FRAILTY CATEGORY

Crosstabulation

FRAILTY

CATEGORY

Total

Non

frail

Pre-

frail

Frail

THYROID

FUNCTIO

N

CATEGOR

Y

Hypothyroidis

m

Count 0 0 1 1

% within

FRAILTY

CATEGOR

Y

0.0% 0.0% 1.4% 0.5%

Subclinical

hypothyroidis

m

Count 0 4 10 14

% within

FRAILTY

CATEGOR

Y

0.0% 4.7% 13.9% 7.0%

Euthyroid

Count 42 82 60 184

% within

FRAILTY

CATEGOR

Y

100.0

% 95.3% 83.3% 92.0%

Subclinical

hyperthyroidis

m

Count 0 0 1 1

% within

FRAILTY

CATEGOR

Y

0.0% 0.0% 1.4% 0.5%

96

Total

Count 42 86 72 200

% within

FRAILTY

CATEGOR

Y

100.0

%

100.0

%

100.0

%

100.0

%

Pearson Chi-Square=15.515** p=0.017

Most of the subjects are euthyroid in all the three groups.13.9% in frail

group (n=10) have subclinical hypothyroidism when compared to pre-

frail group in which 4.7% (n=4) have subclinical hypothyroidism. 1

among the frail group has subclinical hyperthyroism and 1 more in the

frail group has hypothyroidism. With respect to thyroid function category

these three groups show statistical signifance.

97

Table 27 Individual components of frailty phenotype and fT3,fT4,TSH

Individual components of frailty phenotype and fT3,fT4,TSH

Free T4 Free T3 TSH

Mean Median SD SEM Mean Median SD SEM Mean Median SD SEM

WEIGHT

LOSS

no 1.06 1.00 .23 .02 3.31 3.05 .92 .07 3.08 2.43 2.79 .21

yes 1.29 1.30 .28 .05 3.15 2.80 1.20 .23 4.16 2.33 9.39 1.81

WEAKNESS no .96 .94 .16 .02 3.24 3.19 .71 .09 3.32 3.60 1.28 .15

yes 1.16 1.10 .27 .02 3.32 2.90 1.07 .09 3.18 1.90 5.22 .46

SLOWNESS no .97 .94 .20 .02 3.32 3.20 .77 .09 3.18 3.42 1.37 .16

yes 1.16 1.10 .26 .02 3.27 2.90 1.05 .09 3.26 2.30 5.29 .47

EXHAUSTION no 1.01 .97 .21 .02 3.18 3.00 .82 .07 3.02 2.60 2.01 .17

yes 1.27 1.30 .26 .03 3.55 3.00 1.20 .16 3.73 1.70 7.28 .95

LOW

PHYSICAL

ACTIVITY

no 1.01 .97 .21 .02 3.28 3.00 .89 .08 3.52 2.69 4.97 .46

yes 1.20 1.17 .27 .03 3.31 3.00 1.05 .12 2.80 2.00 3.03 .33

WEIGHT

LOSS **p<0.001 0.431 0.224

WEAKNESS **p<0.001 0.567 0.831

SLOWNESS **p<0.001 0.734 0.900

EXHAUSTION **p<0.001 *0.011 0.285

LOW

PHYSICAL

ACTIVITY

**p<0.001

0.804 0.243

Mean fT4 levels in subjects without vs with, weight loss (1.06±0.23 vs

1.29±0.28) , weakness (0.96±0.16 vs 1.16±0.27) ,slowness (0.97±0.20 vs

1.16±0.26), exhaustion(1.01±0.21 vs 1.27) and low physical activity

(1.01±0.21 vs 1.20±1.17) show statistically significant difference with p

value<0.001 for all the five components. And the mean fT4 levels are

high for all the subjects who have scored positive for individual frailty

phenotypic components. Whereas on viewing the result for mean fT3 and

98

TSH levels, only the subjects with and without exhaustion show

significant difference for mean fT3 levels and not for mean TSH levels.

Other components of frailty phenotype criteria don’t show any significant

difference for mean fT3 and TSH levels.

And on correlation it is found that weight loss, gait speed , exhaustion

correlate positively with fT4 levels whereas the correlation is negative for

hand grip and PASE and exhaustion is also found to correlate positively

with TSH.

And then fT4 levels correlate positively with number of components of

frailty.

Table 28 Correlations between individual components of frailty phenotype and fT3 ,fT4 and TSH

Correlations between individual components of frailty phenotype and fT3 ,fT4 and TSH Free T4 Free T3 TSH wt.reduced Pearson Correlation .337** -.196 .102

Sig. (2-tailed) .002 .076 .361 Hand grip (Kg) Pearson Correlation -.239** -.122 -.079

Sig. (2-tailed) .001 .085 .263 15 Ft Walking Time

Pearson Correlation .240** -.060 .229** Sig. (2-tailed) .001 .397 .001 N 200 200 200

No.of days of Exhaustion

Pearson Correlation .390** .036 .018 Sig. (2-tailed) .000 .615 .796

PASE Pearson Correlation -.317** .086 .012 Sig. (2-tailed) .000 .228 .862

No. of components of frailty

Pearson Correlation .575** .036 .025 Sig. (2-tailed) .000 .616 .730

**. Correlation is significant at the 0.01 level (2-tailed).

DISCUSSION

99

DISCUSSION

Our study is a hospital based study and so the prevalence of frailty

is expected to be high as frailty is a condition which will lead the patient

for recurrent hospital visits. It can however be low due to under-reporting

to hospital due to poor functional status or disability.

In this study the overall prevalence of frailty in elderly individuals

is found to be 36%. Of which 59.7% are Sexagenerians and 37.5% are

within the age group 70-79 years. This is in contrary to a study done in

Poland by Bieniek et al(84); where the overall prevalence is 54.2%. Of

which 31.7% are Sexagenerians and 67.6% are Nonagenerians.

This varied prevalence can be attributed to differences in life

expectancies between these two countries. In India it is nearing 70s

whereas in Poland it is nearing 80s. The frail elders in India might have

died at an earlier age.

In our study, there is no significant difference in the prevalence

with respect to gender (49 % frail male vs 51.0% frail females). Various

studies demonstrate the prevalence to be on the higher side in elderly

females than elderly frail males.

Frail elderly persons are hypothesized to have changes in body

composition. On the contrary, in our study, BMI doesn’t find any

100

significant difference between frail& non frail group(24.65(21.56-

27.75)vs 24.32(21.76-26.42)). Moreover BMI is a poor indicator of body

composition. Measurement of lean body mass which is not considered in

this study can give a good picture of body composition.

From this study it is evident that median hand grip , gait speed ,

PASE score show significant difference among Frail, Prefrail and Non

frail groups which is in accordance with most number of studies.

In our study Mean fT4 levels are lesser in Non-frail group

(0.89±0.13) than Pre-frail and Frail groups. Whereas it is higher in frail

elderly (1.29 +/- 0.27) ( f value 67.081 & p value <0.001).It is proposed

that slight differences in Thyroid hormonal axis in Euthyroid subjects

might have relation with frailty. Adding to this hypothesis our study

showed significant difference in mean fT4 levels among Non-frail, Pre-

frail and Frail groups which is consistent with the studies by Virgini et

al(81); (MrOS) research group &Yeap et al(80); (The Health in Men

Study). But those studies include only elderly males, whereas elderly

women are also included in this study.

The study by Virgini et al(81); is a large sampled prospective

cohort study which demonstrated that elderly men with subclinical

hyperthyroidism had an increased likelihood of frailty status ,who on

101

follow up after 5 years had no consistent association with overall frailty

status or frailty components.

Whereas Yeap et al;’s study(80) is a large sampled cross- sectional

epidemiological study. But it utilized the FRAIL scale for assessing

frailty. Comparison between studies which uses different instruments to

assess frailty is difficult.

In this study, we have also tested for fT3 & TSH. Both parameters don’t

show any relation with frailty categories. A study by Veronese et al the

PRO.V.A study (82), a longitudinal study which showed that higher TSH

levels are associated with both prevalent and incident frailty. Whilst in

women we observed that higher TSH levels are associated with an

increased prevalence of frailty at baseline, but lower TSH levels were

associated with an increased risk of frailty in longitudinal analyses.

We have also analysed in this study to look for any relationship

with thyroid hormones, TSH with respect to age &gender(not shown) and

the statistical analysis demonstrated no relationship.

Wang et al(79); conducted a cross sectional study nested within

WHAS I(47)& II in which thyroid autoantibodies which seem to have a

protective role for frailty in women is shown. But we didn’t consider

testing for autoantibodies.

102

We have also looked for correlations between thyroid hormones,

TSH and individual components of frailty and we have found out that

there is a positive correlation between fT4 and weight loss, between fT4

and gait speed, fT4 and exhaustion. Hand grip and physical activity score,

negatively correlate with fT4 levels. Also there is positive correlation

between gait speed and TSH, but there is no correlation between fT3 and

any of the components

A recent study from Italy by Bertoli et al(85); showed fT3, but not fT4

was significantly correlated with frailty score , among ambulatory and

hospitalised patients.

Also we have found positive correlation between number of components

of frailty phenotype criteria and fT4 levels

In our study it is evident that mean fT4 levels are higher in both

Frail elderly males and females and there is statistically significant

difference among the Frail, Pre- frail, Non-frail groups. Also mean fT4

levels correlate independently with the components of frailty phenotype.

STRENGTH

AND

LIMITATIONS

103

STRENGTHS AND LIMITATIONS OF OUR STUDY .

Strengths are

1) Both men and women are included in this study

2) Along with fT4 , fT3 and TSH are also tested.

3) Modified Fried’s Frailty phenotype criteria is employed in our study

for better comparison with future studies.

Limitations are

1) Sample size is small.

2) We didn’t test for changes in thyroid function over time & change of

frailty status

3) Moreover it’s one time cross sectional study. Se we can’t establish a

causative role.

4) Other hormones which are thought to have a causative role are not

tested

5) This study doesn’t include patients who are on thyroxine or on

antithyroid drugs.

104

CONCLUSION

In Elderly, Higher mean fT4 levels nearing upper limit of normal in

Euthyroid is an independent predictor of Frailty.

Thyroxine levels also have independent correlation with components of

Fried’s Frailty Phenotype Criteria.

Scope of Future Studies

Further prospective studies are needed to see whether Frailty status

causes alteration in thyroxine levels or thyroxine hormone has a causative

role in the pathophysiology of Frailty.

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71. Villanueva I, Alva-Sánchez C, Pacheco-Rosado J. The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration. Oxid Med Cell Longev. 2013;2013:1–15.

72. Wrutniak-Cabello C, Casas F, Cabello G. Thyroid hormone action in mitochondria. J Mol Endocrinol. 2001;26(1):67–77.

73. Lanni A, Moreno M, Lombardi A, Goglia F. Thyroid hormone and uncoupling proteins. FEBS Lett. 2003 May 22;543(1–3):5–10.

74. Mullur R, Liu Y-Y, Brent GA. Thyroid Hormone Regulation of Metabolism. Physiol Rev. 2014 Apr 1;94(2):355–82.

75. Mariani E, Ravaglia G, Forti P, Meneghetti A, Tarozzi A, Maioli F, et al. Vitamin D, thyroid hormones and muscle mass influence natural

killer (NK) innate immunity in healthy nonagenarians and centenarians. Clin Exp Immunol. 1999;116(1):19–27.

76. Bowers J, Terrien J, Clerget-Froidevaux MS, Gothié JD, Rozing MP, Westendorp RGJ, et al. Thyroid Hormone Signaling and Homeostasis During Aging. Endocr Rev. 2013 Aug;34(4):556–89.

77. Warner A, Mittag J. Thyroid hormone and the central control of homeostasis. J Mol Endocrinol. 2012 Jun 26;49(1):R29–35.

78. Garasto S, Montesanto A, Corsonello A, Lattanzio F, Fusco S, Passarino G, et al. Thyroid hormones in extreme longevity. Mech Ageing Dev. 2017 Jul;165:98–106.

79. Wang GC, Talor MV, Rose NR, Cappola AR, Chiou RB, Weiss C, et al. Thyroid Autoantibodies Are Associated with a Reduced Prevalence of Frailty in Community-Dwelling Older Women. J Clin Endocrinol Metab. 2010 Mar;95(3):1161–8.

80. Yeap BB, Alfonso H, Paul Chubb SA, Walsh JP, Hankey GJ, Almeida OP, et al. Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study: Thyroxine and frailty. Clin Endocrinol (Oxf). 2012 May;76(5):741–8.

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84. Szewieczek J, Bieniek J, Wilczyński K. Fried frailty phenotype assessment components as applied to geriatric inpatients. Clin Interv Aging. 2016 Apr;453.

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ANNEXURE

Proforma

A STUDY ON ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN ELDERLY

Name Contact

information

Age

Sex

Literacy OP/IP no.

Smoking Never Medical conditions Y/N Duration

Past Hypertension

Current Diabetes mellitus

Alcoholism Never Dyslipidemia

<1 drink/week COPD/BA

1-4drinks/week Old MI/Anginal

episodes

>14 drinks/week Old CVA

Falls Any in past year?

≥2 falls in past

year

Anthropometry

Height

Weight

BMI

Frailty assessment components Data YES NO

Self reported weight loss in prior

12 months

Weakness

Slowness

Exhaustion

Low physical activity

Frailty phenotype

Non Frail

Pre frail

Frail

Thyroid function test

fT4

fT3

fTSH

Impression

INFORMATION SHEET

TITLE : A STUDY ON THE ASSOCIATION OF THYROID FUNCTION AND FRAILTY IN ELDERLY

NAME OF THE INVESTIGATOR:

STUDY CENTRE: Rajiv Gandhi Government General Hospital, Chennai.

NAME OF THE PARTICIPANT: AGE: SEX:

PURPOSE OF THE STUDY: To find whether significant relationship exist between

Thyroid gland function and Frailty in Elderly population.

STUDY DESIGN: Cross sectional study

STUDY PROCEDURE: We are selecting cases as per modified version of the construct (Frailty phenotype criteria) described by Fried et al and if you are found eligible, we may be using your blood sample (3 ml – only once) to measure serum free Thyroxine (fT4), free Triiodothyronine(fT3), Thyroid Stimulating Hormone(TSH) which in any way does not affect your final report or management. POSSIBLE RISKS: No possible risks by means of this study.

POSSIBLE BENEFITS: If this study shows a relationship between them, therapeutic intervention

can be planned accordingly, in future.

CONFIDENTIALITY OF THE INFORMATION OBTAINED FROM THE

PATIENT: The privacy of the patients in this research will be maintained throughout the study. In

the event of any publication or presentation resulting from the research, no personally identifiable

information will be shared.

DECISION TO PARTICIPATE IN THE STUDY: Taking part in this study is voluntary. You are

free to decide whether to participate in this study or to withdraw at any time; your decision will not

result in any loss of benefits to which you are otherwise entitled.

RESULT OF THE STUDY: The results of the special study may be intimated to you at the end of

the study period or during the study if anything is found abnormal which may aid in the management

or treatment.

Signature of Investigator Signature of Participant

Date:

Place:

PATIENT CONSENT FORM

Study Detail : “A STUDY ON ASSOCIATION OF THYROID

FUNCTION AND FRAILTY IN ELDERLY” Study Centre : Rajiv Gandhi Government General Hospital, Chennai.

Patient’s name :

Patient’s Age& Sex :

Identification Number :

Patient may check(�) these boxes

a) I confirm that I have understood the purpose of procedure for the above study. I have the opportunity to ask question and all my questions and doubts have been answered to my complete satisfaction.

�

b) I understand that my participation in the study is voluntary and that I am free to withdraw at any time without giving reason, without my legal rights being affected. �

c) I understand that sponsor of the clinical study, others working on the sponsor’s behalf, the ethical committee and the regulatory authorities will not need my permission to look at my health records, both in respect of current study and any further research that may be conducted in relation to it, even if I withdraw from the study I agree to this access. However, I understand that my identity will not be revealed in any information released to third parties or published, unless as required under the law. I agree not to restrict the use of any data or results that arise from this study.

�

d) I agree to take part in the above study and to comply with the instructions given during the study and faithfully cooperate with the study team and to immediately inform the study staff if I suffer from any deterioration in my health or well being or any unexpected or unusual symptoms.

�

e) I hereby consent to participate in this study. �

f) I hereby give permission to undergo complete clinical examination and hematological tests. �

Signature/Thumb impression Signature of the Investigator

Patient’s Name and Address Study Investigator’s Name

Questionnaire for PASE (Physical activity scale for elderly)

Please complete this questionnaire by either circling the correct response or filling in the blank. Here is an example: During the past 7 days, how often have you seen the sun? [0.] NEVER [1.] SELDOM (1-2 DAYS) [2.] SOMETIMES (3-4 DAYS) [3.] OFTEN (5-7 DAYS) Answer all items as accurately as possible. All information is strictly confidential. Leisure time activity 1. Over the past 7 days, how often did you participate in sitting activities such as reading, watching TV, or doing handcrafts? [0.] NEVER (go to question 2) [1.] SELDOM (1-2 DAYS) (go to question 1.a and 1.b) [2.] SOMETIMES (3-4 DAYS) (go to question 1.a and 1.b) [3.] OFTEN (5-7 DAYS) (go to question 1.a and 1.b) 1.a What were these activities? (open end question) 1.b On average, how many hours did you engage in these sitting activities? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours [3.] more than 4 hours 2. Over the past 7 days, how often did you take a walk outside your home or yard for any reason? For example, for fun or exercise, walking to work, walking the dog, etc [0.] NEVER (go to question 3) [1.] SELDOM (1-2 DAYS) (go to question 2.a) [2.] SOMETIMES (3-4 DAYS) (go to question 2.a) [3.] OFTEN (5-7 DAYS) (go to question 2.a) 2a. On average, how many hours per day did you spend walking? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours [3.] more than 4 hours 3. Over the past 7 days, how often did you engage in light sport or recreational activities such as bowling, golf with a cart, shuffleboard, fishing from a boat or pier or other similar activities? [0.] NEVER (go to question 4) [1.] SELDOM (1-2 DAYS) (go to question 3.a and 3.b) [2.] SOMETIMES (3-4 DAYS) (go to question 3.a and 3.b) [3.] OFTEN (5-7 DAYS) (go to question 3.a and 3.b) 3.a What were these activities? (open end question) 3.b On average, how many hours did you engage in these light sport or recreational activities? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours [3.] more than 4 hours 4. Over the past 7 days, how often did you engage in moderate sport and recreational activities such as doubles tennis, ballroom dancing, hunting, ice skating, golf without a cart, softball or other similar activities? [0.] NEVER (go to question 5) [1.] SELDOM (1-2 DAYS) (go to question 4.a and 4.b) [2.] SOMETIMES (3-4 DAYS) (go to question 4.a and 4.b) [3.] OFTEN (5-7 DAYS) (go to question 4.a and 4.b) 4.a What were these activities? (open end question) 4.b On average, how many hours did you engage in these moderate sport or recreational activities? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours

[3.] more than 4 hours 5. Over the past 7 days, how often did you engage in strenuous sport and recreational activities such as jogging, swimming, cycling, singles tennis, aerobic dance, skiing (downhill or cross-country) or other similar activities? [0.] NEVER (go to question 6) [1.] SELDOM (1-2 DAYS) (go to question 5.a and 5.b) [2.] SOMETIMES (3-4 DAYS) (go to question 5.a and 5.b) [3.] OFTEN (5-7 DAYS) (go to question 5.a and 5.b) 5.a What were these activities? (open end question) 5.b On average, how many hours did you engage in these strenuous sport or recreational activities? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours [3.] more than 4 hours 6. Over the past 7 days, how often did you do any exercises specifically to increase muscle strength and endurance, such as lifting weights or pushups, etc.? [0.] NEVER (go to question 7) [1.] SELDOM (1-2 DAYS) (go to question 6.a and 6.b) [2.] SOMETIMES (3-4 DAYS) (go to question 6.a and 6.b) [3.] OFTEN (5-7 DAYS) (go to question 6.a and 6.b) 6.a What were these activities? (open end question) 6.b On average, how many hours did you engage in these strenuous sport or recreational activities? [0.] Less than 1 hour [1.] 1 but less than 2 hours [2.] 2 - 4 hours [3.] more than 4 hours Household activity 7. During the past 7 days, have you done any light housework, such as dusting or washing dishes? [1.] NO [2.] YES 8. During the past 7 days, have you done any heavy housework or chores, such as vacuuming, scrubbing floors, washing windows, or carrying wood? [1.] NO [2.] YES 9.During the past 7 days, did you engage in any of the following activities? Please answer YES or NO for each item. a. Home repairs like painting, wallpapering, electrical work, etc. b. Lawn work or yard care, including snow or leaf removal, wood chopping, etc. c. Outdoor gardening d. Caring for another person, such as children, dependent spouse, or another adult Work-related activity 10. During the past 7 days, did you work for pay or as a volunteer? [1.] NO [2.] YES (go to questions 10.a and 10.b) 10a. How many hours per week did you work for pay and or as a volunteer? ____ hours 10b. Which of the following categories best describes the amount of physical activity required on your job and or volunteer work?

1. Mainly sitting with some slight arm movement (Examples: office worker, watchmaker, seated

assembly line worker, bus driver, etc.)

2. Sitting or standing with some walking (Examples: cashier, general office worker, light tool and

machinery worker)

3. Walking with some handling of materials generally weighing less than 50 pounds (Examples: mailman,

waiter/waitress, construction worker, heavy tool and machinery worker)

4. Walking and heavy manual work often requiring handling of materials weighting over 50 pounds (Ex:

lumberjack, stone mason, farm or general labourer)

ACTIVITY CATEGORIES

To Compute a PASE Score:

1. Review the leisure time activities recorded by respondents or interviewers to

ensure that sports and recreational activities are correctly classified as light,

moderate, or strenuous. Household activities should not be recorded as sports or

recreation.

2. Determine the frequency value (hours per day in the one-week reporting

period) for each activity. For the walking, exercise, and sports/recreation items,

frequency values are derived from the number of days and hours per day of

activity, as shown in the conversion table at the bottom of the scoring form.

Household activity values are “1” if an activity was reported in the past seven

days and “0” if it was not. The frequency value for paid of volunteer work is the

number of hours worked in the past week divided by seven. The activity

frequency is zero for jobs that involve mainly sitting with slight arm

movements.

3. Multiply the activity weight by the activity frequency for each item.

4. Sum the activity weight by the activity frequency products for all 12 items. It

is recommended that these totals be rounded to the nearest integer. PASE scores

may range from zero to 400 or more.

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753

24.5

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no11

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yes

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58.6

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4.24

Eut

hyro

id

2462

youn

g ol

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063

28ov

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933.

424.

41E

uthy

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2565

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ary

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ver

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147

5826

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over

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are

no6

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50.8

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0.8

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16.9

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al

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old

Fill

iter

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143

7034

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40.

7eu

thyr

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2772

old

old

Mgr

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172

7023

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alun

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23ye

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yes

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90.7

1no

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1.07

3.54

1.18

euth

yroi

d

2872

old

old

Mgr

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150

4921

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norm

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29.6

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e pr

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943

1.88

Eut

hyro

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2984

very

old

Mpr

imar

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noye

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159

4818

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norm

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no33

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pref

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953.

52.

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3084

very

old

Mpr

imar

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157

5823

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3165

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153

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52.

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7832

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1.84

Eut

hyro

id

3362

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g ol

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149

5926

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are

no18

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3460

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Eut

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151

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1.58

euth

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3671

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old

Fill

iter

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ver

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753

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norm

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54.

7eu

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3760

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151

7633

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Eut

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Mhi

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160

7127

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762.

31.

88E

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3965

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148

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1.8

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0.98

Eut

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4063

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176

7825

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are

no31

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1.21

euth

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4163

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168

8630

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32.9

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0.97

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Eut

hyro

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232.

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18E

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4460

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Eut

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149

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Eut

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78E

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Eut

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5266

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95E

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155

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22.

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Eut

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764

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5565

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143

5928

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no35

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Eut

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no16

649

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932.

560.

84E

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5767

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g ol

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ver

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no16

162

23.9

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no15

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82.

75.

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5867

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975.

43E

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5966

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g ol

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166

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0.88

2.9

4.76

Eut

hyro

id

6075

old

old

Fpr

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ver

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yes

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yes

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473

35.2

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yes

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yes

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yes

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lfe

mal

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1.48

3.5

4.7

euth

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d

6175

old

old

Fpr

imar

yne

ver

neve

rno

yes

yes

nono

yes

no15

462

26.1

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yes

16.1

yes

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27.2

yes

3fr

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ale

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l1.

092.

52.

87E

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roid

6267

youn

g ol

dM

mid

dle

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yes

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166

8330

.12

obes

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5.9

no0

no69

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0.97

2.9

4.63

Eut

hyro

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6387

very

old

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imar

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ver

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nono

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171

51.3

17.5

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eno

21.3

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6.5

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no54

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yes

2pr

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ale

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rail

1.12

2.9

1.09

Eut

hyro

id

6487

very

old

Mpr

imar

yne

ver

neve

rno

nono

nono

nono

171

7224

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norm

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eno

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s10

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91.4

no2

pref

rail

mal

e pr

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983

2.48

Eut

hyro

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6567

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g ol

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sch

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29.6

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no79

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0.89

3.42

4.28

Eut

hyro

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6661

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g ol

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ary

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ver

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yes

nono

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143

7536

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obes

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13.6

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ale

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subc

linic

al

hypo

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67yo

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old

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ver

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no14

765

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1.12

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0.84

Eut

hyro

id

6862

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ary

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766

23.6

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are

no6

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no27

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7.9

subc

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al

hypo

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sm69

60yo

ung

old

Mpr

imar

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tne

ver

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sno

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no16

575

.427

.69

over

wei

ght

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are

no32

.98

no6

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no93

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no0

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lm

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l0.

853.

922.

65eu

thyr

oid

7075

old

old

Mpr

imar

yne

ver

neve

rno

yes

nono

yes

nono

152

5322

.93

norm

alun

awar

eno

18ye

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yes

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2ye

s4

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lm

ale

frai

l0.

942.

42.

59E

uthy

roid

7175

old

old

Mpr

imar

yne

ver

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rno

yes

nono

yes

nono

161

7127

.39

over

wei

ght

5ye

s26

.65

yes

9.5

yes

2no

8.6

yes

4fr

ail

mal

e fr

ail

1.65

1.7

2.38

Eut

hyro

id

7269

youn

g ol

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mid

dle

scho

olne

ver

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yes

yes

nono

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147

6027

.76

over

wei

ght

8ye

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yes

14.2

yes

2no

66.4

no3

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mal

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1.39

2.6

2.33

Eut

hyro

id

7363

youn

g ol

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sch

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363

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15.3

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110

no3

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1.45

4.6

3.2

Eut

hyro

id

7470

old

old

Fill

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ate

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ver

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no14

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yes

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90no

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mal

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853.

22.

49E

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roid

7567

youn

g ol

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s14

757

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19.9

6no

6no

1no

105

no0

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lfe

mal

e no

n_fr

ail

0.82

2.9

3.42

Eut

hyro

id

7676

old

old

Mpr

imar

ypa

stpa

stno

yes

nono

nono

no15

758

.423

.69

norm

alun

awar

eno

10.6

6ye

s10

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s6

yes

25.8

yes

4fr

ail

mal

e fr

ail

1.74

3.68

1.5

euth

yroi

d

7776

old

old

Mpr

imar

ypa

stpa

stno

yes

nono

nono

no16

158

22.3

7no

rmal

6ye

s20

yes

10.7

yes

5ye

s39

.49

yes

5fr

ail

mal

e fr

ail

1.4

2.8

1.2

Eut

hyro

id

7880

very

old

Mgr

adua

tene

ver

neve

rno

nono

nono

nono

158

5020

.02

norm

alun

awar

eno

14.1

6ye

s6.

3no

2no

33.6

yes

2pr

efra

ilm

ale

pref

rail

0.95

3.1

4.5

Eut

hyro

id

7980

very

old

Mgr

adua

tene

ver

neve

rno

nono

nono

nono

156

57.5

23.6

2no

rmal

1no

22.6

yes

6no

1no

35ye

s2

pref

rail

mal

e pr

efra

il0.

942.

383.

97E

uthy

roid

8062

youn

g ol

dF

prim

ary

neve

rne

ver

noye

sno

nono

nono

149

7232

.43

obes

e5

yes

13ye

s13

yes

3ye

s27

.2ye

s5

frai

lfe

mal

e fr

ail

1.15

6.4

1.9

T3

toxi

cosi

s/E

uthy

roid

8160

youn

g ol

dF

illit

erat

ene

ver

neve

rno

nono

noye

sno

no14

353

25.9

1ov

erw

eigh

tun

awar

eno

6ye

s18

yes

7ye

s2.

2ye

s4

frai

lfe

mal

e fr

ail

1.1

4.8

1E

uthy

roid

8260

youn

g ol

dF

mid

dle

scho

olne

ver

neve

rno

nono

noye

sno

no14

849

22.3

7no

rmal

unaw

are

no10

.66

yes

8.7

yes

0no

94.6

no2

pref

rail

fem

ale

pref

rail

1.03

2.8

1.83

Eut

hyro

id

8365

youn

g ol

dF

prim

ary

neve

rne

ver

noye

sno

noye

sno

no14

965

29.2

7ov

erw

eigh

t5

yes

18ye

s25

yes

5ye

s27

.2ye

s3

frai

lfe

mal

e fr

ail

1.6

5.6

3.2

T3

toxi

cosi

s/E

uthy

roid

8464

youn

g ol

dM

grad

uate

neve

rne

ver

noye

sye

sno

yes

yes

no17

574

.724

.39

norm

alun

awar

eno

28ye

s8.

2ye

s2

no21

3.2

no2

pref

rail

mal

e pr

efra

il0.

972.

72.

43E

uthy

roid

8564

youn

g ol

dM

high

sch

ool

curr

ent

neve

rno

yes

yes

noye

sye

sno

176

7624

.53

norm

alun

awar

eno

31.3

2no

5.8

no2

no79

.6no

0no

n_fr

ail

mal

e no

n_fr

ail

0.95

3.05

4.36

Eut

hyro

id

8664

youn

g ol

dM

grad

uate

neve

rne

ver

noye

sye

sno

yes

yes

no17

876

23.9

8no

rmal

unaw

are

no31

.32

no8

yes

2no

33.6

yes

2pr

efra

ilm

ale

pref

rail

0.94

3.19

2.41

Eut

hyro

id

8764

youn

g ol

dM

mid

dle

scho

olpa

stne

ver

noye

sno

nono

nono

169

4214

.7un

derw

eigh

tun

awar

eno

11.8

3ye

s6.

2no

2no

22.2

yes

2pr

efra

ilm

ale

pref

rail

0.96

4.5

1.9

T3

toxi

cosi

s/E

uthy

roid

8864

youn

g ol

dM

mid

dle

scho

olpa

stne

ver

noye

sno

nono

nono

160

66.5

25.9

7ov

erw

eigh

tun

awar

eno

32.9

8no

9.5

yes

2no

47.2

yes

2pr

efra

ilm

ale

pref

rail

0.92

2.84

2.72

Eut

hyro

id

8966

youn

g ol

dM

high

sch

ool

neve

rcu

rren

tno

yes

yes

noye

sno

no16

571

26.0

7ov

erw

eigh

t5

yes

14.1

6ye

s6.

8no

4ye

s39

.03

yes

4fr

ail

mal

e fr

ail

1.27

2.9

1.11

Eut

hyro

id

9066

youn

g ol

dM

high

sch

ool

neve

rcu

rren

tno

yes

yes

noye

sno

no16

259

.722

.74

norm

al2.

3no

29.6

6no

9.7

yes

7ye

s5

yes

3fr

ail

mal

e fr

ail

1.41

2.68

2.5

Eut

hyro

id

9166

youn

g ol

dM

illit

erat

ene

ver

past

noye

sye

sno

noye

sno

167

69.5

24.9

2no

rmal

3no

31.3

2no

6.4

no2

no10

6.2

no0

non_

frai

lm

ale

non_

frai

l0.

842.

84.

5eu

thyr

oid

9266

youn

g ol

dF

high

sch

ool

neve

rne

ver

noye

sno

nono

nono

147

7233

.31

obes

e0

no8

yes

9.6

yes

2no

69.2

no2

pref

rail

fem

ale

pref

rail

0.85

4.2

2.3

Eut

hyro

id

9360

youn

g ol

dF

prim

ary

neve

rne

ver

noye

sye

sno

nono

no14

955

24.7

7no

rmal

unaw

are

no13

.66

yes

10ye

s4

yes

60no

3fr

ail

fem

ale

frai

l1.

54.

90.

7T

3 to

xico

sis/

Eut

hyro

id

9470

old

old

Fhi

gh s

choo

lne

ver

neve

rno

yes

nono

nono

no15

177

33.7

7ob

ese

unaw

are

no8.

32ye

s13

.6ye

s4

yes

2.2

yes

4fr

ail

fem

ale

frai

l1.

43.

72.

3E

uthy

roid

9560

youn

g ol

dF

high

sch

ool

neve

rne

ver

nono

yes

nono

nono

155

4819

.97

norm

alun

awar

eno

7ye

s12

.1ye

s2

no17

5no

2pr

efra

ilfe

mal

e pr

efra

il0.

732.

91.

09E

uthy

roid

9662

youn

g ol

dF

prim

ary

neve

rne

ver

nono

nono

nono

yes

142

3919

.34

norm

al8

yes

21.3

3no

19.5

yes

2no

66no

2pr

efra

ilfe

mal

e pr

efra

il1.

012.

93.

05E

uthy

roid

9764

youn

g ol

dF

prim

ary

neve

rne

ver

noye

sno

nono

nono

147

5625

.91

over

wei

ght

unaw

are

no5

yes

19.2

yes

5ye

s25

yes

4fr

ail

fem

ale

frai

l1.

322.

34.

74E

uthy

roid

9867

youn

g ol

dF

high

sch

ool

neve

rne

ver

nono

nono

nono

no15

856

22.4

3no

rmal

unaw

are

no10

yes

13.3

yes

2no

58.6

no2

pref

rail

fem

ale

pref

rail

0.95

2.5

2.4

Eut

hyro

id

9960

youn

g ol

dF

illit

erat

ene

ver

neve

rno

nono

nono

nono

157

4919

.87

norm

alun

awar

eno

7ye

s34

.5ye

s1

no12

1no

2pr

efra

ilfe

mal

e pr

efra

il1.

072.

31.

18eu

thyr

oid

100

80ve

ry o

ldF

prim

ary

neve

rne

ver

noye

sye

sno

nono

no14

238

18.8

4no

rmal

unaw

are

no1

yes

19.5

yes

2no

66no

2pr

efra

ilfe

mal

e pr

efra

il1.

12.

51.

06eu

thyr

oid

101

73ol

d ol

dF

prim

ary

neve

rne

ver

nono

nono

yes

nono

145

4119

.5no

rmal

7ye

s4

yes

27.9

yes

4ye

s81

.8no

4fr

ail

fem

ale

frai

l0.

572.

450

.8hy

poth

yroi

dism

102

60yo

ung

old

Fpr

imar

yne

ver

neve

rno

yes

yes

yes

yes

nono

142

5527

.27

over

wei

ght

2no

16.4

8ye

s13

.1ye

s2

no60

.91

no2

pref

rail

fem

ale

pref

rail

0.86

4.3

2.6

Eut

hyro

id

103

70ol

d ol

dM

illit

erat

ene

ver

neve

rno

yes

nono

nono

no16

650

.418

.29

unde

rwei

ght

0.5

no14

.16

yes

10.5

yes

2no

111.

8no

2pr

efra

ilm

ale

pref

rail

0.7

33.

7eu

thyr

oid

104

70ol

d ol

dM

illit

erat

ene

ver

neve

rno

yes

nono

nono

no15

939

.915

.78

unde

rwei

ght

unaw

are

no15

.34

yes

6.6

no1

no8.

6ye

s2

pref

rail

mal

e pr

efra

il1.

074

0.7

euth

yroi

d

105

65yo

ung

old

Mm

iddl

e sc

hool

curr

ent

curr

ent

noye

sye

sno

yes

nono

166

47.8

17.3

4un

derw

eigh

tun

awar

eno

12ye

s13

.2ye

s5

yes

5ye

s4

frai

lm

ale

frai

l1.

532.

30.

16su

bclin

ical

hy

poth

yroi

dism

106

60yo

ung

old

Fgr

adua

tene

ver

neve

rno

noye

sno

nono

no15

654

22.1

9no

rmal

0no

14.1

6ye

s12

.7ye

s2

no65

no2

pref

rail

fem

ale

pref

rail

1.28

2.8

1.4

euth

yroi

d

107

62yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

yes

nono

158

55.5

22.2

3no

rmal

unaw

are

no14

.16

yes

14.5

yes

2no

58.6

no2

pref

rail

fem

ale

pref

rail

1.18

2.86

3.81

euth

yroi

d

108

60yo

ung

old

Fhi

gh s

choo

lne

ver

neve

rno

nono

nono

nono

145

5224

.73

norm

al3

no1

yes

7.3

yes

2no

213.

51no

2pr

efra

ilfe

mal

e pr

efra

il0.

94.

56.

7su

bclin

ical

hy

poth

yroi

dism

109

63yo

ung

old

Fpr

imar

yne

ver

neve

rno

noye

sno

nono

no15

872

28.8

4ov

erw

eigh

tun

awar

eno

12ye

s11

.6ye

s5

yes

60.9

1no

3fr

ail

fem

ale

frai

l1.

492

3.8

euth

yroi

d

110

65yo

ung

old

Mill

iter

ate

past

curr

ent

nono

nono

yes

nono

169

72.5

25.3

8ov

erw

eigh

t2.

5no

18.8

3ye

s12

.5ye

s1

no13

6.88

no2

pref

rail

mal

e pr

efra

il1.

012.

93.

05E

uthy

roid

111

65yo

ung

old

Mill

iter

ate

past

curr

ent

nono

nono

yes

nono

172

52.4

17.7

1un

derw

eigh

tun

awar

eno

22.6

6ye

s6.

8no

1no

47.2

yes

2pr

efra

ilm

ale

pref

rail

12.

80.

5eu

thyr

oid

112

65yo

ung

old

Mill

iter

ate

past

curr

ent

nono

nono

yes

nono

171

53.4

18.2

6un

derw

eigh

tun

awar

eno

34.6

4no

6.7

no1

no79

.6no

0no

n_fr

ail

mal

e no

n_fr

ail

0.81

2.86

3.84

euth

yroi

d

113

60yo

ung

old

Mpr

imar

ycu

rren

tne

ver

noye

sye

sno

nono

no15

558

.824

.47

norm

al1

no22

.6ye

s6

no1

no35

yes

2pr

efra

ilm

ale

pref

rail

0.75

3.9

1.3

euth

yroi

d

114

60yo

ung

old

Mpr

imar

ycu

rren

tne

ver

noye

sye

sno

nono

no16

773

.426

.31

over

wei

ght

-4.2

no31

.32

no10

.7ye

s2

no39

.03

yes

2pr

efra

ilm

ale

pref

rail

1.03

2.65

1.83

Eut

hyro

id

115

65yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

yes

nono

nono

147.

543

19.7

6no

rmal

unaw

are

no11

.83

yes

9.5

yes

2no

124.

3no

2pr

efra

ilfe

mal

e pr

efra

il1.

282.

81.

4eu

thyr

oid

116

70ol

d ol

dM

illit

erat

epa

stne

ver

nono

yes

noye

sye

sno

175

6721

.87

norm

alun

awar

eno

31.3

2no

5.8

no1

no11

7.29

no0

non_

frai

lm

ale

non_

frai

l0.

784.

14.

12E

uthy

roid

117

60yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sye

sno

nono

no14

851

23.2

8no

rmal

unaw

are

no15

.32

yes

9.3

yes

0no

119.

25no

2pr

efra

ilfe

mal

e pr

efra

il1.

13.

52.

4eu

thyr

oid

118

80ve

ry o

ldF

prim

ary

neve

rne

ver

nono

yes

nono

nono

156

4920

.13

norm

al2

no7

yes

12.8

yes

2no

175

no2

pref

rail

fem

ale

pref

rail

0.83

2.7

1.21

euth

yroi

d

119

72ol

d ol

dM

high

sch

ool

neve

rne

ver

noye

sye

sye

sno

nono

164

6122

.67

norm

alun

awar

eno

13ye

s5.

7no

2no

63.2

yes

2pr

efra

ilm

ale

pref

rail

1.12

3.94

1.09

Eut

hyro

id

120

72ol

d ol

dM

high

sch

ool

neve

rne

ver

noye

sye

sye

sno

nono

175

75.2

24.5

6no

rmal

unaw

are

no28

yes

8.2

yes

2no

213.

2no

2pr

efra

ilm

ale

pref

rail

1.2

4.6

1eu

thyr

oid

121

72ol

d ol

dM

prim

ary

neve

rne

ver

noye

sye

sno

nono

no17

673

.423

.69

norm

alun

awar

eno

32.9

8no

5.5

no2

no21

3.2

no0

non_

frai

lm

ale

non_

frai

l0.

863.

24.

7eu

thyr

oid

122

60yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sno

nono

nono

149

8638

.73

obes

e2

no10

.64

yes

10.2

yes

4ye

s13

6.88

no3

frai

lfe

mal

e fr

ail

1.3

5.8

0.7

euth

yroi

d

123

60yo

ung

old

Mill

iter

ate

curr

ent

curr

ent

nono

nono

nono

no16

944

15.4

unde

rwei

ght

unaw

are

no11

.83

yes

6.2

no1

no25

.8ye

s2

pref

rail

mal

e pr

efra

il0.

752.

63.

11eu

thyr

oid

124

60yo

ung

old

Mill

iter

ate

curr

ent

curr

ent

nono

nono

nono

no16

359

22.2

1no

rmal

unaw

are

no23

yes

8ye

s2

no12

2.4

no2

pref

rail

mal

e pr

efra

il1.

182.

52.

4E

uthy

roid

125

60yo

ung

old

Mpr

imar

ycu

rren

tcu

rren

tye

sye

sno

nono

nono

169

51.3

17.9

6un

derw

eigh

t2

no29

.66

no6.

2no

2no

80no

0no

n_fr

ail

mal

e no

n_fr

ail

0.79

3.6

4.11

euth

yroi

d

126

70ol

d ol

dF

illit

erat

ene

ver

neve

rno

noye

sno

nono

no13

639

21.0

8no

rmal

unaw

are

no5

yes

8.1

yes

2no

27.2

yes

3fr

ail

fem

ale

frai

l1.

263.

62.

3eu

thyr

oid

127

70ol

d ol

dM

illit

erat

epa

stne

ver

noye

sye

sye

sno

nono

171

59.7

20.4

1no

rmal

unaw

are

no29

.66

no6.

3no

2no

119.

25no

0no

n_fr

ail

mal

e no

n_fr

ail

0.9

3.4

2.76

euth

yroi

d

128

65yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

nono

no15

549

20.3

9no

rmal

5ye

s13

yes

9.3

yes

4ye

s11

4.6

no4

frai

lfe

mal

e fr

ail

1.04

2.6

1.57

euth

yroi

d

129

60yo

ung

old

Fm

iddl

e sc

hool

neve

rne

ver

noye

sye

sye

sno

nono

141

6934

.7ob

ese

5ye

s6

yes

12.7

yes

5ye

s33

.6ye

s5

frai

lfe

mal

e fr

ail

1.3

4.1

4.3

euth

yroi

d

130

62yo

ung

old

Mill

iter

ate

past

neve

rno

yes

yes

nono

nono

160

5923

.04

norm

alun

awar

eno

29.6

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6.9

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1.8

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frai

lm

ale

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l0.

742.

764.

81E

uthy

roid

131

63yo

ung

old

Fpr

imar

yne

ver

neve

rno

noye

sye

sno

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152

5021

.64

norm

al2

no18

no6.

1no

2no

110

no0

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frai

lfe

mal

e no

n_fr

ail

0.73

2.7

2.7

Eut

hyro

id

132

64yo

ung

old

Mpr

imar

ypa

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ver

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sno

noye

sno

163

58.6

22.0

5no

rmal

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.66

no9.

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s7

yes

8.6

yes

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mal

e fr

ail

1.14

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0.79

euth

yroi

d

133

65yo

ung

old

Mill

iter

ate

past

neve

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nono

162

46.7

17.7

9un

derw

eigh

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frai

lm

ale

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653

3.96

euth

yroi

d

134

70ol

d ol

dM

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erat

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ver

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no15

758

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norm

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eno

15.3

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yes

27.2

yes

4fr

ail

mal

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ail

1.22

2.3

0.64

euth

yroi

d

135

69yo

ung

old

Fill

iter

ate

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ver

noye

sno

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150

5524

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norm

al2

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54.4

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883.

574.

53E

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roid

136

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no16

073

28.5

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472.

91.

2E

uthy

roid

137

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ver

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873

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ght

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no31

.32

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93.6

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0.77

3.34

5.45

euth

yroi

d

138

66yo

ung

old

Mill

iter

ate

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162

43.2

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no39

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3fr

ail

mal

e fr

ail

1.7

3.1

2.3

euth

yroi

d

139

66yo

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old

Mill

iter

ate

neve

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tno

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nono

nono

154

5523

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norm

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awar

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no61

.71

yes

3fr

ail

mal

e fr

ail

1.39

1.89

2.8

Eut

hyro

id

140

65yo

ung

old

Mgr

adua

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ver

neve

rno

yes

nono

nono

no16

659

.521

.59

norm

al0.

5no

36.3

no6.

7no

2no

94.6

no0

non_

frai

lm

ale

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frai

l0.

773.

233.

75eu

thyr

oid

141

70ol

d ol

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illit

erat

ene

ver

curr

ent

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nono

no16

556

.620

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norm

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eno

14.1

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8.6

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4fr

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mal

e fr

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0.9

3.7

23.7

subc

linic

al

hypo

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270

old

old

Mill

iter

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160

63.6

24.8

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rmal

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are

no18

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yes

10.5

yes

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6ye

s4

frai

lm

ale

frai

l1.

433.

781.

7E

uthy

roid

143

69yo

ung

old

Mpr

imar

ycu

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tne

ver

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sno

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169

6121

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norm

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6.6

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no94

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mal

e no

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0.81

3.17

4.82

euth

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144

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neve

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yes

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938

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are

no15

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6.5

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0.8

1.7

1.3

euth

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d

145

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23.5

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no29

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192.

782.

4E

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146

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ary

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yes

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no16

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are

no34

.64

no6.

8no

1no

97.7

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ale

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862.

72.

38eu

thyr

oid

147

74ol

d ol

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ary

past

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yes

yes

yes

yes

no16

041

.416

.17

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are

no34

.64

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8no

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5.8

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922.

794.

8eu

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148

60yo

ung

old

Fill

iter

ate

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no14

846

21no

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are

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8.7

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93.6

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mal

e pr

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044

0.7

euth

yroi

d

149

80ve

ry o

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ene

ver

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yes

yes

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yes

no14

960

27.0

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erw

eigh

tun

awar

eno

11.8

3ye

s14

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s3

yes

30ye

s4

frai

lfe

mal

e fr

ail

1.36

3.6

3.9

euth

yroi

d

150

60yo

ung

old

Fm

iddl

e sc

hool

neve

rne

ver

noye

sye

sno

noye

sno

132

4827

.54

over

wei

ght

3no

14.1

6ye

s10

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2no

172.

4no

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ilfe

mal

e pr

efra

il1.

122.

91.

09E

uthy

roid

151

80ve

ry o

ldF

illit

erat

ene

ver

neve

rno

yes

yes

nono

yes

no14

852

23.7

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are

no17

.64

yes

10.5

yes

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s63

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ail

fem

ale

frai

l1.

645.

143.

25T

3 to

xico

sis/

Eut

hyro

id

152

67yo

ung

old

Mpr

imar

yne

ver

curr

ent

noye

sno

nono

nono

158

5622

.43

norm

alun

awar

eno

17.6

4ye

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.5ye

s2

no1

no2

pref

rail

mal

e pr

efra

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174.

141

Eut

hyro

id

153

67yo

ung

old

Mpr

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yne

ver

curr

ent

noye

sno

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169

73.2

25.6

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t2.

5no

18.8

3ye

s12

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s1

no13

6.88

no2

pref

rail

mal

e pr

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4.9

5eu

thyr

oid

154

75ol

d ol

dM

prim

ary

neve

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rren

tno

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nono

nono

161

65.8

25.3

8ov

erw

eigh

t14

.2ye

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.96

yes

16ye

s4

yes

28.6

yes

5fr

ail

mal

e fr

ail

1.5

2.3

4.63

euth

yroi

d

155

75ol

d ol

dM

prim

ary

neve

rcu

rren

tno

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nono

nono

164

6323

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norm

al7

yes

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yes

2no

6.4

yes

4fr

ail

mal

e fr

ail

1.7

2.78

2.68

euth

yroi

d

156

68yo

ung

old

Mhi

gh s

choo

lpa

stne

ver

nono

yes

yes

yes

yes

no16

463

23.4

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are

no29

.66

no6.

5no

2no

117.

29no

0no

n_fr

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mal

e no

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ail

0.92

1.93

3.1

euth

yroi

d

157

65yo

ung

old

Mill

iter

ate

neve

rpa

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nono

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sno

no17

282

27.7

1ov

erw

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8ye

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yes

58.6

yes

4fr

ail

mal

e fr

ail

1.4

5.7

1.7

euth

yroi

d

158

65yo

ung

old

Mill

iter

ate

neve

rpa

stno

nono

noye

sno

no16

065

.425

.54

over

wei

ght

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are

no18

.83

yes

10.5

yes

5ye

s8.

6ye

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frai

lm

ale

frai

l0.

872.

40.

5eu

thyr

oid

159

71ol

d ol

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grad

uate

neve

rne

ver

nono

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nono

no16

454

20.0

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rmal

1no

34.6

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6.8

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6.2

no0

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frai

lm

ale

non_

frai

l0.

953.

624.

78E

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roid

160

74ol

d ol

dM

prim

ary

neve

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tno

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147

6027

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over

wei

ght

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s16

.48

yes

15ye

s2

no66

.4no

3fr

ail

mal

e fr

ail

1.59

3.2

3.96

euth

yroi

d

161

74ol

d ol

dM

prim

ary

neve

rcu

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tno

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nono

nono

160

47.7

18.6

3no

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are

no18

.83

yes

14ye

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yes

8.6

yes

4fr

ail

mal

e fr

ail

0.8

4.5

8.8

subc

linic

al

hypo

thyr

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sm16

267

youn

g ol

dF

high

sch

ool

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ver

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yes

no14

751

23.6

norm

al3

no23

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no6.

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111.

8no

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n_fr

ail

fem

ale

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frai

l0.

973.

982.

68E

uthy

roid

163

66yo

ung

old

Mpr

imar

yne

ver

neve

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noye

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noye

sno

167

74.2

26.6

over

wei

ght

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no31

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no6.

3no

2no

94.6

no0

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frai

lm

ale

non_

frai

l0.

834.

134.

5eu

thyr

oid

164

66yo

ung

old

Mpr

imar

yne

ver

neve

rno

noye

sno

noye

sno

168

7526

.6ov

erw

eigh

t-4

.2no

31.3

2no

10.7

yes

2no

33.6

yes

2pr

efra

ilm

ale

pref

rail

0.8

4.1

4eu

thyr

oid

165

66yo

ung

old

Mpr

imar

yne

ver

neve

rno

noye

sno

noye

sno

167

8731

.19

obes

eun

awar

eno

33no

6no

0no

25.8

yes

1pr

efra

ilm

ale

pref

rail

1.03

2.68

1.83

Eut

hyro

id

166

60yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

nono

no14

643

20.1

7no

rmal

unaw

are

no5

yes

16.8

yes

6ye

s2.

2ye

s4

frai

lfe

mal

e fr

ail

1.1

1.7

3.8

euth

yroi

d

167

75ol

d ol

dF

illit

erat

ene

ver

neve

rno

nono

nono

nono

147

5023

.13

norm

alun

awar

eno

4ye

s12

.1ye

s4

yes

35ye

s4

frai

lfe

mal

e fr

ail

1.02

2.8

1.17

euth

yroi

d

168

75ol

d ol

dF

illit

erat

ene

ver

neve

rno

nono

nono

nono

147

5525

.45

over

wei

ght

unaw

are

no11

.84

yes

10.5

yes

3ye

s66

.4no

3fr

ail

fem

ale

frai

l1.

463.

71.

5E

uthy

roid

169

70ol

d ol

dF

illit

erat

ene

ver

neve

rno

yes

nono

yes

nono

151

6227

.19

over

wei

ght

2no

2ye

s10

.3ye

s7

yes

8.6

yes

4fr

ail

fem

ale

frai

l1.

042

0.12

euth

yroi

d

170

60yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

nono

no15

072

32ob

ese

unaw

are

no15

.32

yes

6.2

no1

no69

.2no

1pr

efra

ilfe

mal

e pr

efra

il0.

972.

72.

43E

uthy

roid

171

62yo

ung

old

Fpr

imar

yne

ver

neve

rno

noye

sno

yes

nono

148

62.5

28.5

3ov

erw

eigh

tun

awar

eno

20no

6.4

no0

no93

.65

no0

non_

frai

lfe

mal

e no

n_fr

ail

0.74

3.8

4.34

euth

yroi

d

172

76ol

d ol

dF

prim

ary

neve

rne

ver

nono

nono

nono

no14

545

21.4

norm

alun

awar

eno

2ye

s11

.8ye

s2

no15

yes

3fr

ail

fem

ale

frai

l1.

242.

38.

07su

bclin

ical

hy

poth

yroi

dism

173

76ol

d ol

dF

prim

ary

neve

rne

ver

nono

nono

nono

no15

083

36.8

8ob

ese

2no

9.51

yes

9.8

yes

3ye

s13

2.1

no3

frai

lfe

mal

e fr

ail

1.45

4.96

0.68

T3

toxi

cosi

s/E

uthy

roid

174

80ve

ry o

ldF

illit

erat

ene

ver

neve

rno

yes

nono

nono

no14

547

22.3

5no

rmal

unaw

are

no2

yes

9.1

yes

0no

52.2

no2

pref

rail

fem

ale

pref

rail

1.1

2.7

1.21

euth

yroi

d

175

65yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

nono

no15

266

28.5

6ov

erw

eigh

t6

yes

17.6

6ye

s13

.6ye

s1

no30

yes

4fr

ail

fem

ale

frai

l1.

222.

12.

16eu

thyr

oid

176

65yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sno

nono

yes

no15

452

21.9

2no

rmal

5ye

s17

.66

no6

no1

no10

6.2

no1

pref

rail

fem

ale

pref

rail

1.17

5.4

1E

uthy

roid

177

66yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sno

nono

yes

no14

055

28.0

6ov

erw

eigh

tun

awar

eno

17.6

6ye

s14

.7ye

s4

yes

33.6

yes

4fr

ail

fem

ale

frai

l1.

112.

51.

58eu

thyr

oid

178

70ol

d ol

dF

illit

erat

ene

ver

neve

rye

sye

sno

nono

nono

154

5422

.76

norm

al3

no9.

51ye

s12

.1ye

s5

yes

33.6

yes

4fr

ail

fem

ale

frai

l1.

253

3.71

euth

yroi

d

179

66yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sye

sno

yes

nono

148

5726

.02

over

wei

ght

unaw

are

no17

yes

6no

1no

105

no1

pref

rail

fem

ale

pref

rail

1.2

51.

6E

uthy

roid

180

66yo

ung

old

Fill

iter

ate

neve

rne

ver

noye

sno

nono

nono

148

6831

.04

obes

eun

awar

eno

11.8

yes

5.3

no0

no11

9.25

no2

pref

rail

fem

ale

pref

rail

0.96

3.5

2.4

euth

yroi

d

181

60yo

ung

old

Fill

iter

ate

neve

rne

ver

nono

nono

nono

no13

649

26.4

9ov

erw

eigh

t2

no13

yes

13ye

s2

no17

2.4

no2

pref

rail

fem

ale

pref

rail

1.17

5.4

1E

uthy

roid

182

60yo

ung

old

Fpr

imar

yne

ver

neve

rno

yes

yes

nono

nono

141

5326

.65

over

wei

ght

unaw

are

no19

no12

.5ye

s6

yes

58.6

no2

pref

rail

fem

ale

pref

rail

1.15

2.5

2.4

Eut

hyro

id

183

68yo

ung

old

Fgr

adua

tene

ver

neve

rno

yes

yes

yes

nono

no14

853

24.1

9no

rmal

unaw

are

no19

.96

no6.

4no

0no

122.

4no

0no

n_fr

ail

fem

ale

non_

frai

l1.

082.

83.

88E

uthy

roid

184

70ol

d ol

dM

illit

erat

epa

stne

ver

noye

sye

sye

sno

nono

164

6423

.79

norm

alun

awar

eno

13ye

s5.

7no

2no

63.2

yes

2pr

efra

ilm

ale

pref

rail

1.4

4.9

1.9

T3

toxi

cosi

s/E

uthy

roid

185

70ol

d ol

dF

prim

ary

neve

rne

ver

noye

sye

sno

nono

no15

459

24.8

7no

rmal

unaw

are

no18

.8no

6.6

no1

no94

.6no

0no

n_fr

ail

fem

ale

non_

frai

l0.

934.

14.

26E

uthy

roid

186

70ol

d ol

dM

illit

erat

epa

stne

ver

noye

sye

sye

sno

nono

153

4820

.5no

rmal

unaw

are

no28

yes

10ye

s2

no10

6.2

no2

pref

rail

mal

e pr

efra

il1.

053.

240.

93E

uthy

roid

187

60yo

ung

old

Fm

iddl

e sc

hool

neve

rne

ver

nono

nono

nono

no14

560

25.0

7ov

erw

eigh

t0

no23

.99

no10

yes

2no

97.7

no1

pref

rail

fem

ale

pref

rail

1.1

4.3

2.6

Eut

hyro

id

188

80ve

ry o

ldF

illit

erat

ene

ver

neve

rno

yes

nono

nono

no14

356

27.3

8ov

erw

eigh

tun

awar

eno

19no

12.5

yes

6ye

s58

.6no

2pr

efra

ilfe

mal

e pr

efra

il1.

122.

70.

84E

uthy

roid

189

60yo

ung

old

Mhi

gh s

choo

lne

ver

neve

rno

nono

nono

nono

170

6321

.79

norm

alun

awar

eno

31.3

2no

6.3

no0

no22

1.8

no0

non_

frai

lm

ale

non_

frai

l0.

763.

984.

62E

uthy

roid

190

72ol

d ol

dm

illit

erat

epa

stpa

stye

sye

sye

sno

nono

no16

758

20.7

9no

rmal

unaw

are

no13

.66

yes

10.6

yes

3ye

s22

.2ye

s4

frai

lm

ale

frai

l1.

743.

680.

26su

bclin

ical

hyp

erth

yroi

dism

191

72ol

d ol

dm

illit

erat

epa

stpa

stye

sye

sye

sno

nono

no16

244

.216

.84

unde

rwei

ght

2.8

no22

.66

yes

11.1

yes

2no

39.0

3ye

s3

frai

lm

ale

frai

l1.

363.

40.

16su

bclin

ical

hy

poth

yroi

dism

192

60yo

ung

old

fhi

gh s

choo

lne

ver

neve

rno

noye

sno

noye

sno

153

5322

.64

norm

alun

awar

eno

18.8

no6.

2no

1no

30ye

s1

pref

rail

fem

ale

pref

rail

1.2

42.

1E

uthy

roid

193

67yo

ung

old

fpr

imar

yne

ver

neve

rno

nono

noye

sno

no14

8.5

5424

.32

norm

al-1

no17

.99

no11

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s4

yes

93.6

no2

pref

rail

fem

ale

pref

rail

1.3

5.1

3.5

Eut

hyro

id

194

60yo

ung

old

fpr

imar

yne

ver

neve

rye

sno

nono

nono

no15

655

22.6

norm

alun

awar

eno

14.1

6ye

s13

.5ye

s2

no69

.2no

2pr

efra

ilfe

mal

e pr

efra

il1.

23.

90.

91E

uthy

roid

195

65yo

ung

old

mill

iter

ate

curr

ent

curr

ent

yes

yes

yes

yes

yes

yes

no17

152

.718

.02

unde

rwei

ght

unaw

are

no21

.3ye

s6.

8no

3ye

s39

.03

yes

3fr

ail

mal

e fr

ail

1.6

4.6

1.1

frai

l

196

65yo

ung

old

Mill

iter

ate

neve

rne

ver

noye

sno

nono

nono

159

7128

.08

over

wei

ght

5ye

s28

yes

12.5

yes

4ye

s33

.6ye

s5

frai

lm

ale

frai

l1.

42.

91.

2E

uthy

roid

197

65yo

ung

old

Fpr

imar

yne

ver

neve

rno

yes

yes

noye

sye

sno

162

59.7

22.7

4no

rmal

unaw

are

no23

no10

.2ye

s4

yes

47.2

yes

3fr

ail

fem

ale

frai

l1.

33.

90.

8E

uthy

roid

198

67yo

ung

old

mpr

imar

ypa

stne

ver

yes

noye

sno

yes

nono

162

48.1

18.3

2un

derw

eigh

t-1

.7no

7.16

yes

10ye

s4

yes

50.8

yes

4fr

ail

mal

e fr

ail

1.53

3.8

0.8

euth

yroi

d

199

67yo

ung

old

mpr

imar

ypa

stne

ver

yes

noye

sno

yes

nono

148

6228

.3ov

erw

eigh

t8

yes

12.9

6ye

s14

.3ye

s2

no66

.4no

3fr

ail

mal

e fr

ail

1.65

1.7

1.32

Eut

hyro

id

200

60yo

ung

old

mhi

gh s

choo

lne

ver

neve

rno

noye

sno

nono

no17

180

27.3

5ov

erw

eigh

t2

no9.

51ye

s10

.2ye

s3

yes

65ye

s4

frai

lm

ale

frai

l1.

485.

71.

3eu

thyr

oid