View
6
Download
0
Category
Preview:
Citation preview
1
Thyroid Disorders in Older Adults
Alvin M. Matsumoto, M.D.
Professor, Department of Medicine
Acting Head, Division of Gerontology & Geriatric Medicine
University of Washington School of Medicine
Geriatric Research, Education and Clinical Center
V.A. Puget Sound Health Care System
Seattle, WA
Geriatric Health Series
May 13, 2014Matsumoto 05/13/14
2
Thyroid Disorders in Older AdultsClinical Presentation and Diagnosis
• Atypical, nonspecific
– Cognition, depression, falls, function
• Multiple co-morbidities
– Alter presentation, mask or mimic thyroid disease
• Symptoms attributed to “old age”
• Diagnosis difficult
– Rely on thyroid function tests (TFTs)
– TFTs misleading with non-thyroidal illness (NTI)
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 1
3
Thyroid Disorders in Older AdultsTreatment and Prognosis
• Clearance and sensitivity– Start low/go slow, replacement dose
• Co-morbidities– Compromised thyroid dose (e.g. angina)
– Worsened by inappropriate treatment (e.g. osteoporosis, mood, cognition)
– Predispose to drug interaction, poor compliance
• Prognosis– Worse for well-differentiated thyroid cancer
– Lymphoma, anaplastic cancer more common
– Affected by co-morbid illnesses
Matsumoto 05/13/14
4
Clinical Evaluation of Thyroid Disease
• Function
– Hyperthyroid, hypothyroid or euthyroid?
– Non-thyroidal illness (sick euthyroid)?
– Clinical, TSH and free T4
• Anatomy
– Normal?
– Goiter (enlargement)?
• Diffuse or multinodular
– Solitary nodule?
• Benign or malignant
• Age may modify presentation and management
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 2
5
Physiology
TRH
TSH
T4
T3
rT3
T2’s
5’-deiodinase
+
+
Hypothalamus
Pituitary
Thyroid
99.97%
bound
99.7%
bound
Iodine
free T4Matsumoto 05/13/14
6
Physiology: Age-Related Changes
TRH
TSH
T4
T3
rT3
T2’s
5’-deiodinase
+
+
Hypothalamus
Pituitary
Thyroid
99.97%
bound
99.7%
bound
Iodine
free T4Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 3
7
Non-Thyroidal Illness (NTI): Effects on TFTs
TRH
TSH
T4
T3
rT3
T2’s
5’-deiodinase
+
+
Hypothalamus
Pituitary
Thyroid
99.97%
bound
99.7%
bound
Iodine
NTI
NTINTI
NTI
free T4Matsumoto 05/13/14
Refer
8
TSH in Thyroid and Non-Thyroidal Disease
Hyperthyroid Thyroid
Autonomy
(Euthyroid)
Non-thyroidal
Illness
Central Primary
Hypothyroid
Normal
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 4
9
Thyroid Function Tests
• TSH
– Outpatient screening
– Not sufficient alone in sick patients
– Glucocorticoids, dopamine, fasting, head trauma
– Transiently during recovery from illness
• Free T4 (fT4)
– Free T4 equilibrium dialysis
• Gold standard, but send-out
– Free T4 direct estimates
• Available in local labs
• Unreliable when extremely high or low TBG
Matsumoto 05/13/14
10
Sick Euthyroid Syndromes
• Low T4 syndrome ( total T4, normal fT4)
– TBG
– T4 binding inhibitor
– Dilantin ( fT4)
• Low T3 syndrome ( total T3)
– Acute or chronic illness
– -blocker, glucocorticoids, amiodarone
• High T4 syndrome ( total T4, normal fT4)
– TBG
– Acute T4 T3
– Psychiatric hospitalization ( fT4)
Matsumoto 05/13/14 Refer
Thyroid (Matsumoto), NWGEC Spring 2014 5
11
Thyroid Disorders in Older AdultsScreening
• Failure to thrive, cognitive impairment, chronic
disability
• Well elderly with h/o thyroid or autoimmune
disease, unexplained depression or cognitive
dysfunction, cholesterol
• Atrial fibrillation, CVD or CHF, osteoporosis
• Asymptomatic well-elderly – controversial
Matsumoto 05/13/14
12
Risk of Developing Overt Hypothyroidism
and Hyperthyroidism
MPJ Vanderpump, Clin Endocrinol, 1995Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 6
13
HypothyroidismSymptoms
• Dry skin, sweating
• Cold intolerance
• Hoarseness
• Weight gain
• Constipation
• Paresthesias, hearing
• Fatigue, weakness, muscle cramps
• Depressed mood
Matsumoto 05/13/14
14
HypothyroidismSigns
• Slow movements
• Dry skin and coarse hair
• Cold skin
• Periorbital puffiness
• Bradycardia
• Slow relaxation of reflexes
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 7
15
Hypothyroidism in Older AdultsManifestations
• Dry skin, hair loss, periorbital edema, cold
intolerance (myxedema)
• Paresthesias (carpal tunnel), ataxia, cognitive
dysfunction
• Depression, apathy, psychosis
• Weight gain, cholesterol and TG, edema
• Myopathy, arthralgia
• Bradycardia, pericardial effusion, CHF
Matsumoto 05/13/14
16
Hypothyroidism: Bradycardia
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 8
17
Hypothyroidism: Cardiomegaly Due to
Pericardial Effusion
Untreated After thyroid hormone
replacementMatsumoto 05/13/14
18
HypothyroidismDiagnosis
• fT4
• TSH
– TSH in primary hypothyroidism
– Normal to TSH in secondary hypothyroidism
– Transient or TSH with NTI
• TSH, normal fT4 (subclinical)
• Anti-thyroid peroxidase (anti-TPO) Ab (Hashimoto’s)
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 9
19
HypothyroidismCauses
• Primary
– Hashimoto’s disease (autoimmune) most common
– Neck irradiation (lymphoma, head & neck CA)
– Thyroiditis (recovery phase)
– Surgical removal
– Iodine, lithium, amiodarone, anti-thyroid drugs,
sunitinib
– [Iodine deficiency, enzymatic defects, agenesis]
• Secondary
– Hypothalamic-pituitary disease
• Destructive process, e.g. tumor
Matsumoto 05/13/14 Refer
20
Hypothyroidism in Older Adults
• Common (2-10%) – most subclinical
• Atypical, nonspecific presentation
– Insidious, often subclinical
– Neuropsychiatric (confusion, cognition, neuropathy,
weakness, ataxia, hearing)
– Myxedema (cold, puffiness)
– Cardiovascular (bradycardia, CHF, effusions)
– Anemia, hyponatremia, CPK, cholesterol/TG
• Falls, mobility, urinary incontinence
• NTI affects thyroid function tests
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 10
21
Subclinical Hypothyroidism
• TSH, normal fT4 (subclinical)
– Prevalence 4-10%, with age
• 1-2% per year overt hypothyroidism
• Greater TSH (> 10)
• Goiter
• Low-normal fT4
• Anti-TPO Ab (Hashimoto’s)
• 50% TSH normalizes
• Associated with CVD, CHF and CV mortality
– TSH > 10
• Thyroid hormone treatment outcomes?
Matsumoto 05/13/14
22
Hypothyroidism in Older AdultsTreatment
• Symptoms, goiter, TSH > 10, anti-TPO – treat
• Asymptomatic and TSH 4-10 – monitor
• Goal – normal TSH (and fT4)
• T4 (levothyroxine) fasting
– Start low (25-50 g/d)/go slow ( 25-50 g/d q 4-6 wks)
– More rapid for severe
– Requirement less (~110 g/d)
– Ca, bisphosphonates, Fe, PPIs, resins absorption
– Dilantin, carbamazepine clearance
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 11
23
HyperthyroidismSymptoms
• Nervousness
• Sweating, heat intolerance
• Dyspnea, palpitations
• Fatigue, weakness
• Weight loss, appetite
• Eye symptoms
• Hyperdefecation
Matsumoto 05/13/14
24
HyperthyroidismSigns
• Thyroid enlargement, bruit
• Ophthalmopathy, lid retraction and lag
• Hyperkinesis
• Tremor
• Warm, moist hands and skin
• Tachycardia, atrial fibrillation
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 12
25
Hyperthyroidism in Older AdultsManifestations
• Palpitations, atrial fibrillation, CHF
• Depression, apathy, lethargy, irritability
• Appetite, weight loss, nausea, constipation
• Proximal muscle wasting and weakness
• Peripheral neuropathy
Matsumoto 05/13/14
26
Hyperthyroidism due to Toxic Multinodular
Goiter in the Elderly
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 13
27
Graves Disease
• Autoimmune disease
– TSI TSH receptor
• Hyperthyroidism with diffuse goiter
• Opthalmopathy infiltrative
– Exophthalamos (proptosis), EOMs
– Chemosis (edema), periorbital soft tissue
• Dermopathy infiltrative
– Localized (pretibial) myxedema
– Thyroid acropachy (nails)
• Elderly may not have any of these signs
Matsumoto 05/13/14 Refer
28
Thyroid Palpation: Landmarks
Thyroid lobe
(“rule of thumb”)
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 14
29
Thyroid Palpation: Landmarks
Thyroid lobe
(“rule of thumb”)
Matsumoto 05/13/14
30
Hyperthyroidism: Atrial fibrillation
Slow ventricular response
may be present in elderly
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 15
31
HyperthyroidismDiagnosis
• fT4
• Sometimes only T3 (T3 thyrotoxicosis)
• Undetectable or TSH
• Normal T4 and T3 (subclinical)
• Thyroid-stimulating immunoglobulins – TSI
(Graves)
Matsumoto 05/13/14
32
Radioactive Iodine Uptake (RAIU)
DDx of Hyperthyroidism
• High uptake
– Graves disease
– Toxic multinodular goiter or adenoma
– [TSH-secreting tumor, choriocarcinoma]
• Low to no uptake
– Thyroiditis
– Exogenous (20-40%) or facticious
– Iodine-induced (contrast, exogenous)
– [Struma ovarii, metastatic thyroid cancer]
Matsumoto 05/13/14
Refer
Thyroid (Matsumoto), NWGEC Spring 2014 16
33
Hyperthyroidism in Older Adults
• Not uncommon (0.5-2.0%) – most subclinical
• Atypical or subclinical presentation
– No heat intolerance, tachycardia, hyperkinesis
– Apathetic, depressed
– Anorexia, weight loss, constipation, weakness
– Dyspnea, slow atrial fibrillation, CHF
• Graves disease most common (atypical)
• Multinodular goiter more common
• T3 thyrotoxicosis
Matsumoto 05/13/14
34
Subclinical Hyperthyroidism
• TSH, normal fT4 (subclinical)
– Prevalence 1-5% > 65 years old
• Progression to overt hyperthyroidism
– Greater TSH (< 0.1)
– High-normal fT4 or total or free T3
– Goiter
– Graves disease (thyroid-stimulating
immunoglobulins, TSI)
• Associated with atrial fibrillation, CVD, CV
mortality, hip fracture, cognitive impairment, QOL
– TSH < 0.1
• Anti-thyroid or RAI treatment outcomes?Matsumoto 05/13/14 Refer
Thyroid (Matsumoto), NWGEC Spring 2014 17
35
Hyperthyroidism in Older AdultsTreatment
• Symptoms and TSH < 0.1 (undetectable)
• Asymptomatic and TSH < 0.3 (low)
– Atrial fibrillation
– Osteoporosis
– Heart disease
– Cognitive impairment
Matsumoto 05/13/14
36
Hyperthyroidism in the ElderlyTreatment of Graves Disease
• Symptomatic/prior to radioactive iodine
– blockers
• Propanolol 40-120 mg/d
• Anti-thyroid drugs
• Methimazole 5-15 mg/d
• Radioactive iodine
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 18
37
Nodular Thyroid Disease
• Multinodular
– Usually benign
– Suspicious nodule may be cancer
• Solitary nodule – most nonpalpable
– Most benign and cold on scan
– Some cancer
• Cysts
– Usually benign and cold on scan
Matsumoto 05/13/14
38
Nontoxic Multinodular Goiter: Excessive Iodine
Intake May Induce Hyperthyroidism
Kombu Kelp 1500 mg =
600-900 g iodine vs.
RDA = 150 g iodine
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 19
39
Nontoxic Multinodular GoiterManagement
• Issues
– Local compressive symptoms
– Cosmetic
– Risk iodine-induced hyperthyroidism
– Risk of malignancy
• Treatment
– No treatment
– TSH suppression with T4 – not recommended
• Poor (30-50%) partial response
• Risk of symptomatic hyperthyroidism ( risk in elderly with autonomous secretion)
– Surgery
Matsumoto 05/13/14
40
Solitary Thyroid Nodule
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 20
41
Solitary Thyroid Nodule
• Common (prevalence ~5%)
– Palpable in ~7% women and 2% men
– Prevalence with neck irradiation and in elderly
– ~50% at autopsy
– Greater incidental detection with ultrasound
• Majority benign ~85%
– ~15% malignant (most clinically suspicious)
Matsumoto 05/13/14
42
Prevalence of Thyroid Nodules
EL Mazzaferri, NEJM, 1993Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 21
43
Solitary Thyroid NoduleCommon Causes
• Benign 85%
– Colloid nodule (in multinodular goiter)
– Follicular adenoma
– Cyst (simple or hemorrhagic)
– Hashimoto’s disease
• Malignant 15%
– Papillary or follicular carcinoma (85%)
– Medullary or anaplastic carcinoma
– Other (lymphoma, metastatic)
Matsumoto 05/13/14
44
Solitary Thyroid NoduleRisk of Cancer
• Male, child or elderly
• History of neck irradiation
• Family history of medullary thyroid cancer/MEN
• Recent size, large (> 4 cm)
• Rock hard
• Hoarseness, fixed, dysphagia, dyspnea
• Lymphadenopathy, distant metastasis
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 22
45
Solitary Thyroid NoduleManagement
• Surgery if suspicious for cancer
• Fine needle aspiration biopsy (FNAB) US-guided
– Nodule > 1 cm
– Suspicious US
Matsumoto 05/13/14 Refer
46
Nodular Thyroid Disease in the Elderly
• Multinodular goiter very common (60-90%)
– Autonomy risk of hyperthyroidism
– Resistant to T4 suppression
– Sensitive to iodine
• Solitary nodules also very common
– Mortality with well-differentiated thyroid carcinoma
– Lymphoma and anaplastic thyroid carcinoma
– More sensitive to hyperthyroidism with TSH
suppression
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 23
47
Well-Differentiated (Papillary or Follicular)
Thyroid Cancer
• Occult or intrathyroidal ~ normal survival
• Poor prognostic factors survival
– Large tumor (>2.5 cm)
– Age > 40 yrs old
– Local invasion (capsule or blood vessel)
– Distant metastasis (mediastinum, lung, bone)
– Less well-differentiated anaplastic
– Local lymph nodes?
Matsumoto 05/13/14 Refer
48
Increased Incidence and Death Rate of
Thyroid Cancer with Aging
JL Young Jr, NCI Pub NIH81-2330, 1981Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 24
Matsumoto 05/13/1449
Siegel R, et al, CA Cancer J Clin 64:9-29, 2014
Secular Increase in Incidence and Mortality with Thyroid Cancer
50
Well-Differentiated (Papillary or Follicular)
Thyroid Cancer
• Treatment
– Near-total or total thyroidectomy
– RAI ablation
– Chronic TSH suppression
• High – intermediate risk
– Capsular or blood vessel invasion
– Incomplete resection
– Distant metastases
– Cervical node metastases
– Aggressive histology
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 25
Matsumoto 05/13/14 51
Grogan RH, et al, J Clin Endocrinol Metab 97:1645-1653, 2012
Post-Operative Complications with
Thyroidectomy in Older Patients
Matsumoto 05/13/14 52Mazzaferri EL, Jiang SM, Am J Med 97:418-428, 1994
Thyroid Hormone Suppression Recurrence
of Thyroid Cancer Post-Thyroidectomy
Thyroid (Matsumoto), NWGEC Spring 2014 26
Matsumoto 05/13/14 53McLeod DS, et al, Lancet 381:1046-1057, 2013
Degree of TSH SuppressionConsider Risk of Cancer Progression vs. Risk of
Adverse Effects
Refer
54
Thyroid Disorders in Older AdultsSummary
• Clinically atypical, nonspecific, confounded by co-morbidities, attributed to “old age”
• Subclinical > overt disease
• Measure fT4 and TSH if sick, misleading in NTI
• Subclinical hypothyroidism common
• Replacement dose lower
• Hyperthyroidism very atypical presentation
• Thyroid cancer prognosis worse
• TSH suppression consider risk of thyroid cancer progression vs. risk of adverse effects
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 27
55
Thyroid Disorders in Older AdultsReferences
• Boelaert K. Thyroid dysfunction in the elderly. Nat Rev Endocrinol 9:`94-204, 2013
• Visser ED, et al. Thyroid disorders in older adults. Endocrinol Metab Clin N Am 42:287-303, 2013
• Papaleontiou M, Haymart MR. Approach to and treatment of thyroid disorders in the elderly. Med Clin N Am 96:297-310, 2012
• Mitrou P, et al. Thyroid disease in older people. Maturitas 70:5-9, 2011
• McLeod DA, et al. Controversies in primary treatment of low-risk papillary thyroid cancer. Lancet 381:1046-1057, 2013
Matsumoto 05/13/14
Thyroid (Matsumoto), NWGEC Spring 2014 28
Recommended