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Unrestricted © Siemens Healthcare Diagnostics Inc. 2015 All rights reserved.
Update on Thyroid DisordersLinda Rogers, PhD, DABCC, FACB
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Objectives
1. Define hypothyroidism and hyperthyroidism and describe the common clinical presentationsand the general laboratory diagnosis of each
2. Understand and describe the differences in the reference ranges of key thyroid tests inpediatric patients and pregnant women
3. Describe Grave’s Disease and the utilization of the thyroid stimulating antibodies (TSI) assayin its diagnosis and management.
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Agenda
1. Overview of the thyroid endocrine system
2. Hypothyroidism: clinical presentation and the general laboratory diagnosis
3. Hyperthyroidism: clinical presentation and the general laboratory diagnosis
4. Grave’s Disease and the utilization of the thyroid stimulating antibodies (TSI) assay in itsdiagnosis and management
5. Thyroid disorders and pregnancy
6. Pediatric reference ranges
7. Clinical case studies
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Epidemiology of Thyroid Dysfunction: United States
80%
27 millionAmericans
Affects
Most commonendocrine disorder
are female
More commonthan diabetes
http://www.suite101.com/content/how-many-americans-suffer-thyroid-disorders-a135894
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Thyroid Dysfunction and Diagnosis
The right test…
facilitates correct diagnosis.at the right time…
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Thyroid Hormone Regulation
http://endocrinediseases.org/thyroid/thyroid_background.shtml; Scott MG. Tietz Textbook of Clinical Chemistryand Molecular Diagnostics, 5th edition (Kindle). St. Louis, MO: Elsevier Saunders; 2011.
Anterior Pituitary
Posterior Pituitary
Hypothalamus
TSHReceptor
T3
T4
T3
T4T4
T4
T4
T4
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Thyroid Hormone Regulation
Hypothalamus
Anterior pituitary
TRHTRHTRH
T3
T4T4
T4T4T3
T3
T4T3
T4
TSHreceptor
http://endocrinediseases.org/thyroid/thyroid_background.shtml; Scott MG. Tietz Textbook of Clinical Chemistryand Molecular Diagnostics, 5th edition (Kindle). St. Louis, MO: Elsevier Saunders; 2011.
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I-
I-
I-
I- I-
I-
I-
I-
I-I-
I-
TPO
Thyroid Hormone Regulation
Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206.
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ThyrocyteLacuna
Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206.
Thyroid Hormone Regulation
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Thyroid Hormones are Essential
Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206.
Alters gene expression, protein production.
Regulates metabolism – proteins, fats, carbohydrates.
Essential for normal development of the fetusand newborn brain, and somatic tissue.
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Laboratory Tests Aid Diagnosis
• TSH
• Third generation TSH
• Free T4
• Total T4
• Free T3
• Total T3
• T3 uptake
• Anti-thyroid peroxidase antibody
• Anti-thyroglobulin antibody
• Thyroglobulin
• Thyroxine-binding globulin
• TRAb
• TSI(TSAb)
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61. British Thyroid Association.http://www.british-thyroid-association.org/info-for-patients/Docs/TFT_guideline_final_version_July_2006.pdf
Lab Tests
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Hypothyroidism
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Hypothyroidism: Basics
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.
Secondary and Tertiary DiseaseDisease of the hypothalmusDisease of the pituitary
Primary DiseaseDisease of the thyroid gland
Insufficient Thyroid HormoneT4 and/or T3
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Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25.McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.
FamilyHistory
ConsistentSymptoms
FemaleGender
AutoimmuneDisease
Age
Hypothyroidism: Risk Factors
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Classification of Hypothyroidism by Etiology
• Thyroid dysgenesis• Thyroid dysmorphogenesisCongenital
• hCG-mediated thyrotoxicosis• TSH-mediated thyrotoxicosis• Hemochromatosis• Tumors• Sarcoidosis
Other Diseases
• Drugs (amiodarone, stavudine, thalidomide)• Iodine-induced hyperthyroidism
Drugs
• Subacute/acute thyroiditis (subacute/acute, lymphocytic, autoimmune)• Thyroid surgery or irradiation• Thyroid cancer–related thyrotoxicosis
Gland Injury
Diseases
Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25.
Etiology
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Hypothyroidism
• Fatigue • Sexual disturbances
• Muscle weakness • Menstrual disturbance
• Impaired memory • Impaired fertility
• Impaired learning • Mental disturbances (depression)
• Weight gain • Sleep disturbances (sleepiness)
• Alterations in appetite • Constipation
• Cold intolerance • Hair loss
• Dry skin
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.
Nonspecific Symptoms
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Impact of Hypothyroidism
Myxedema Coma• Life threatening, mortality rates 25% to 75%.• Extreme hypothermia (24˚C to 32.2˚C).• Complication of long term hypothyroidism, rare.
Cardiovascular Disease/Dysfunction• Hypercholesterolemia.• Impaired cardiac function (diastolic and systolic).
• Increased systemic vascular resistance.• Decreased cardiac output.
Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25
Rodriguez I. J Endocrinol. 2004 Feb;180(2):347-50
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Evaluating Hypothyroidism
Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25. Baskin et al.,Endo Pract. 2002; 6:458-69. Bahn, et al, Thyroid. 2011; 21:593-646.
ComprehensivePhysical Exam
Serology: TSH, Total and Free T3 and T4
Myohan CC-BY-3.0
Drahreg01 CC-BY-SA-4.0
Imaging
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“A TSH assay should always be used asthe primary test to establish the diagnosisof primary hypothyroidism. The mostvaluable test is a sensitive measurementof TSH level.”Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25.American Association of Clinical Endocrinologists. Endocrine Practice. 2002 Nov/Dec 8;(6):458-69.
American Association of Clinical Endocrinology(AACE) Recommendations: Hypothyroidism
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Primary Hypothyroidism: Overt Disease
Structural abnormalitiesThyroid scanUltrasound
Test Result
TSH High
Free T4 Low
Free T3 Low/normal
TgAbs May be present
Anti-TPO May be present
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.American Association of Clinical Endocrinologists. Endocrine Practice. 2002 Nov/Dec 8;(6):458-69.
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Primary Hypothyroidism: Subclinical Disease
Test Result
TSH High
Free T4 Normal
Free T3 Normal
TgAbs May be present
Anti-TPO May be present
Progresses to overt diseasein 3% to 20% of cases
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.American Association of Clinical Endocrinologists. Endocrine Practice. 2002 Nov/Dec 8;(6):458-69.
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General Serology for Hypothyroidism
Hypothyroid
Subclinicalhypothyroid
TSH FT4 FT3
Normal Normal
T3
T4T3
T4T4T3
T3
T4T3
T4
Baskin et al., Endo Pract. 2002; 6:458-69.Vadiveloo T, et al. J Clin Endocrinol Metab. 2011 Jan;96(1):E1-8.
DS2
Slide 22
DS2 Should FT4 & FT3 have the #s as subscripts? Same question throughout.Dina Salzer, 3/7/2016
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Hypothyroidism: Monitoring Treatment
TSH and Free T4
• Every 6-8 weeks until normalized• Every 3–6 months• Annually
McDermott MT. Ann Intern Med. 2009 Dec 1;151(11):ITC61.American Association of Clinical Endocrinologists. Endocrine Practice. 2002 Nov/Dec 8;(6):458-69. British Thyroid Association.http://www.british-thyroid-association.org/info-for-patients/Docs/TFT_guideline_final_version_July_2006.pdf
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Hyperthyroidism
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“The sensitive TSH assay is the singlebest screening test for hyperthyroidismand in most outpatient clinical situations,the serum TSH is the most sensitive testfor detecting mild (subclinical) thyroidhormone excess or deficiency.”Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25.American Association of Clinical Endocrinologists. Endocrine Practice. 2002 Nov/Dec 8;(6):458-69.
American Association of Clinical Endocrinology(AACE) Recommendations: Hyperthyroidism
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Devereaux, et al. Emerg Med Clin North Am. 2014;32:277-92.
Hyperthyroidism: Many Nonspecific Symptoms
Hyperthyroidism - SymptomsNervousness and irritability Exertional intolerance and dyspneaPalpitations and tachycardia Menstrual disturbance (decreased flow)Heat intolerance or increased sweating Impaired fertilityTremor Mental disturbancesWeight loss or gain Sleep disturbances (including insomnia)Alterations in appetite Changes in vision, photophobia,
eye irritation, diplopia, or exophthalmosFrequent bowel movements or diarrhea Fatigue and muscle weaknessDependent lower-extremity edema Thyroid enlargementSudden paralysis Pretibial myxedema
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Hyperthyroidism: Risk Factors
iodine53
I126.90
Intropin CC BY 3.0
Ladenson PW. Thyroid. ACP Medicine. Decker Intellectual Properties; 2010. p.1-25.
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Evaluating Hypothyroidism
Landenson PW. Thyroid. ACP Medicine. 2010. p.1-25. Baskin et al.,Endo Pract. 2002; 6:458-69. Bahn, et al, Thyroid. 2011; 21:593-646.
ComprehensivePhysical Exam
Serology: TSH, Total and Free T3 and T4
Myohan CC-BY-3.0
Drahreg01 CC-BY-SA-4.0
Imaging
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General Serology for Hyperthyroidism
T3
T4T3
T4T4T3
T3
T4T3
T4
Hypothyroid
Subclinicalhypothyroid
TSH FT4 FT3
Normal Normal
Baskin et al., Endo Pract. 2002; 6:458-69.Vadiveloo T, et al. J Clin Endocrinol Metab. 2011 Jan;96(1):E1-8.
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A Diagnostic Algorithm: Hyperthyroidism
TRAb TSI Anti-TPO Ab
Normal No furthertesting
Free T3 or Total T3
Normal or Decreased
Increased
T3 thyrotoxicosis
Normal
Retest in 2–4 mos
Increased
Test forautoimmune
disease
Mueller AF, et al. Neth J Med. 2008 Mar;66(3):134-42.
TSH
Low
Free T4 or Total T4
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Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206.Devereaux, et al.. Emerg Med Clin North Am. 2014;32:277-92.
Severe Complications of Hyperthyroidism
Thyroid storm• Confusion, psychosis, spasticity, convulsions coma• Hyperthermia• Nausea, vomiting, diarrhea• Irregular pulse, tachycardia, hypertension followed by hypotension, cardiac collapse, heart failure• Fatal without treatment, requires immediate therapy: 20% to 50% mortality even with treatment
Cardiovascular disease• Decreased systemic vascular resistance• Increased cardiac preload and output• Systolic hypertension• Congestive heart failure
Osteoporosis
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Grave’s Disease
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Graves’ Disease
Ophthalmopathy
Jonathan Trobe, MD. CC-BY 3.00
Diffuse Goiter• Symmetrical• Firm
Drahreg01 CC-BY-SA-3.0
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Autoimmunity in Graves’ Disease
Anti-TSH Ab
TSH
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The TSH receptor
74 aa
B A
Thyrocyte
Membrane (lipid bilayer)
Stimulating epitope
Blocking epitope
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TSH Autoantibodies
T3
T4 T4
T4
T3T4
T4
T4
Thyroid stimulating antibody (TSAb) /Thyroid stimulating immunoglobulin (TSI)
Thyroid blocking antibody (TBAb) /Thyrotropin blocking inhibiting
immunoglobulin (TBII)
Neutral antibody
TSH
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Effect of Thyroid Stimulating Antibody
TRHT3
T4 T4
T4
T4T3
T4
T4
T4
T3T4
T4
T4T3
T4 T4
TSH T3 T4
TSHTSH
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Effect of Thyroid Blocking Antibody
TRH
T4
T3
T4
T4
TSHTSHTSH
T3TSH T4
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TRAb Nomenclature Review
Antibody type Action EffectTRAb Binds to TSH receptor antibodies to either inhibit
or stimulateHypothyroidism orHyperthyroidism (depending onantibody type and possibly ratio)
TbAb Blocks TSH binding, depresses T3/T4 production HypothyroidismTSAb Blocks TSH binding, stimulates T3/T4 production Hyperthyroidism
Assay type Antibody type(s) detectedTRAb TBAb (blocking) and TSAb (stimulating)Anti-TSHR TBAb (blocking) and TSAb (stimulating)TBII TBAb (blocking) and TSAb (stimulating)TSI TSAb only stimulating
DS1
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DS1 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal texton a click.Dina Salzer, 3/7/2016
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Gupta M. Siemens webinar. 2013.Laurberg, et al. Eur J Endocrinol. 1998 Dec;139(6):584-6.
Overview of TSI Utility in Graves’ Disease
Indication Comments
Diagnosis of Graves’ Disease • Differential diagnosis (vs. other hyperthyroid disease)
Ophthalmopathy • Differential diagnosis in• unilateral orbitopathy• orbitopathy with euthyroid status• orbitopathy with hypothyroid status
• Treatment guidance
Pregnancy • Useful in pregnant women with• current or past treatment• previous children with neonatal thyrotoxicosis
• Fetal hyperthyroidism diagnosis
Neonatal hyperthyroidism • Prediction and diagnosis
ATD treatment • Helps predicts remission
Gupta Bahn, et al. Thyroid. 2011;21(6):593-646. http://www.thyroid.org/what-is-a-goiter/.Eckstein, et al. Med Klin (Munich). 2009 May 15;104(5):343-8
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Graves’ Disease Diagnosis
• Clinical signs and TSH, free T4,and/or free T3 results
• TSI(+) → Graves’ Disease
• TSI detected in 77.8%–100% ofGD patients
Nonautoimmunehyperthyroidism
TSH FT4FT3
T3 toxicosis
Graves’ Disease
TSI
Neg
Neg /
Bahn, et al. Thyroid. 2011;21:593-646.Macchia E, et al. Autoimmunity. 1989;3(2):103-12.Takasu N, et al. J Endocrinol Invest. 1997 Sep;20(8):452-61.
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Better Diagnostic Accuracy of TSI vs. TRAb
• 182 sera: 79 GD, 103 non-GD
• TSI assay demonstrated100% sensitivity100% specificity100% diagnostic accuracy
• TRAb assay: 96.9% diagnostic accuracy
100
80
60
40
20
0100806040200
TSI assay
TRAb assay
Sen
sitiv
ity1 – SpecificityFranz, et al. Poster presented at ÖGLMKC Congress, 2007, Vienna.
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AutoimmuneHyperthyroidism?(Graves’ Disease)
Non-Autoimmune Hyperthyroidism?(e.g. toxic multi-nodular goiter, toxic
thyroid adenoma)
Further investigation necessary
Is it Graves’ Disease?
Graves’ Disease Non-AutoimmuneHyperthyroidism
Is it Graves’ Disease?
DS4
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DS4 Do you want me to recreate this chart? It looks okay but it is placed as an image so the font is wrong.Dina Salzer, 3/7/2016
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McKee, et al.. Am J Manag Care. 2012;18:e1-14.
TSI : Time and Cost Advantages
Based on a study by McKee and Peyerl, the use of algorithmsthat incorporate TSI testing early in the primary care settingresulted in:
• 46% less time to diagnosis (5.3 weeks earlier)
• 47% annual payer cost savings ($698,892 or $760/person)
• Fewer misdiagnoses
• Faster referral from primary care physicians to endocrinologists
• Fewer specialist visits
• Increased patient productivity
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Total Payer Costs of GD Diagnosis
$1,480,328
$780,918
47% decrease =$698,892
McKee, et al.. Am J Manag Care. 2012;18:e1-14.
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McKee, et al.. Am J Manag Care. 2012;18:e1-14.
Average Time to Diagnosis
11.7 weeks
6.4 weeks
46% decrease
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Bahn, et al. Thyroid 2011;21(6):593-646.
Summary: Utility of TSI Testing in ATD, Radioiodine,and Surgical Treatments
Treatment Type TSI Utility
Antithyroid drugs Prognostic during treatmentHighà relapseLowà remissionPrognostic during treatmentHighà relapseLowà remissionTherapy guidance in 3rd trimesterHighà continue ATD
Radioiodine Treatment guidance for patients at high risk of worsening Graves’ ophthalmopathyHigh (pretreatment)à avoid radioiodine therapy
Surgery Treatment guidance for anticipated pregnancy (with 4–6 months of treatment)High (pretreatment)à surgery preferred over radioablation
DS5
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DS5 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal texton a click.Dina Salzer, 3/7/2016
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Pregnancy
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National Endocrine and Metabolic Diseases Information Service. Pregnancy and Thyroid Disease. April 2012. NIH Publication No. 12–6234.http://www.endocrine.niddk.nih.gov/pubs/pregnancy/. Accessed March 13, 2014
Pregnancy and the Thyroid
• Pregnancy has a profound impact on the thyroid gland and thyroidfunction tests
• Serum TBG concentrations rise almost two-fold because estrogenincreases TBG production
• To maintain adequate free thyroid hormone concentrations during thisperiod, T4 and T3 production by the thyroid gland increase
• Total T4 and T3 concentrations rise during the first half of pregnancy,plateauing at approximately 20 weeks of gestation, at which time a newsteady state is reached and the overall production rate of thyroidhormones returns to prepregnancy rates
• Considerable homology between the beta-subunits of hCG and TSH.As a result, hCG has weak thyroid-stimulating activity
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Physiologic change Thyroid test change
é TBG é Total T3, é Total T4
First trimester hCG elevation é Free T4, ê TSH
é Plasma volume é Pool size T3, T4
é Type III 5-deiodinase é Degradation of T3, T4
Thyroid enlargement ê Serum thyroglobulin
é Iodine clearance ê Hormone production in deficiency
Bahn, et al. Thyroid. 2011;21:593-646. De Groot, et al. J Clin Endocrinol Metab. 2012;97:2543-65. AACE. Endo Pract. 2002;8:458-69. 2006 update.Lee, et al. Am J Obstet Gynecol. 2009;200:260.e1 Galofre, et al. J Womens Health (Larchmt). 200918:1847-56. Lazarus JH. Br Med Bull. 2011;97:137-48.Abalovich, et al., J Clin Endocrinol Metab. 2007;92(8 Suppl):S1-47.
Pregnancy: Physiological Changes
DS6
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DS6 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal texton a click.Dina Salzer, 3/7/2016
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Hypothyroidism in Pregnancy
• Subclinical hypothyroidism has an estimated prevalence of 2-3%
• Overt hypothyroidism is seen in about 0.3-0.5% of pregnancies
• The most common cause of hypothyroidism is the autoimmunedisorder known as Hashimoto’s thyroiditis
• Endemic iodine deficiency accounts for most hypothyroidism inpregnant women worldwide while chronic autoimmune thyroiditisis the most common cause of hypothyroidism in iodine sufficientparts of the world
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Complications of Hypothyroidism in Pregnancy
Maternal complications:• miscarriages• anemia• pre-eclampsia• abruptio placenta• postpartum hemorrhage
Neonatal complications:• premature birth• low birth weight• increased neonatal respiratory distress
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Hyperthyroidism in Pregnancy
• Hyperthyroidism occurs in about 0.2-0.4% of all pregnancies
• The most common cause of maternal hyperthyroidism duringpregnancy is the autoimmune disorder Graves’ disease
• Must be distinguished from gestational transient thyrotoxicosis, aself-limiting hyperthyroid state due to the thyroid stimulatoryeffects of beta-hCG
• Untreated hyperthyroidism is associated with an increased riskof severe pre-eclampsia and up to a four-fold increased risk oflow birth weight deliveries
Thyroid. The Merck Manual. 18th ed. 2006. p.1192-1206.Devereaux, et al.. Emerg Med Clin North Am. 2014;32:277-92.
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Pregnancy: Congenital HyperthyroidismTSAb is Predictive of Graves’ Disease vs Other Thyrotoxicoses
Excess hormone present at birth
Rare• 0.01% of pregnancies
Maternal TSAb levels• Higher levels, higher risk for poor outcomes
Fetal disease• Preterm delivery• Death• Growth restriction
Abalovich, et al. J Clin Endocrinol Metab. 2007;92(8 Suppl):S1-47. Polak, et al. Horm Res. 2006;65:235–42Lazarus JH. British Medical Bulletin. 2010;23:1-12. Endocrine Society’s Clinical Guidelines. J Clin Endocr Metab. 2007;92:S1-S47.
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Gupta M. Siemens webinar. 2013.Laurberg, et al. Eur J Endocrinol. 1998 Dec;139(6):584-6.
TSI Assay - Clinical Utility
Indication Comments
Diagnosis of Graves’ Disease Aids in differentiating GD from other forms ofthyrotoxicosis
OphthalmopathyUseful for differential diagnosis of GD in patients withunilateral orbitopathy or orbitopathy with euthyroid orhypothyroid status
Pregnancy Useful in women who are currently on antithyroid drugtherapy, have had either radioactive iodine or surgeryfor thyrotoxicosis, or have had children with neonatalneonatal thyrotoxicosis
Neonatal Test neonate if mother’s TRAb levels are high inthird trimester
Therapy guidance/prognosis Helps identify patients on ATD who are more likelyto remit
Gupta Bahn, et al. Thyroid. 2011;21(6):593-646. http://www.thyroid.org/what-is-a-goiter/.Eckstein, et al. Med Klin (Munich). 2009 May 15;104(5):343-8
DS8
Slide 55
DS8 the text is in the tables and appears on a click - you'll see it in show mode - for the sake of animation, there is a white box over the text which fades to reveal texton a click.Dina Salzer, 3/7/2016
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Summary: TSI Testing
AidsDiagnosis
Patients diagnosedand treated sooner
Can beAutomatedReady to use.Improved lab
efficiency
SpecificDetects ONLY
stimulating Abs,the cause of GD
(differs from TRAB)
Your Solution to Graves’ Disease Testing
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Children are not small adults…
We are pleased to announce the launch of Siemens Thyroid Pediatric Reference Intervals
Thyroid function abnormalities areamong the most commonendocrine problems in children
Children’s thyroid hormone levelsshow a clear age dependency.Therefore age-specific referenceintervals are critical for properclinical interpretation of test results
One of the most challengingaspects of establishing pediatricreference intervals is theavailability of well-characterizedhealthy pediatric samples andsufficient blood volume to conductstudies across multiple assays
Repeated requests from ourglobal customers over the yearshave been to establish Siemenssystem specific pediatric thyroidreference intervals
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Project Objective
ObjectiveTo design and run appropriate studies to establishpediatric reference intervals for thyroid hormonesacross all major Siemens platforms for infant, childand adolescent age groups
Scope• Assays: 3rd Gen TSH, FT4, FT3, T4, T3• IA Systems: ADVIA Centaur systems, IMMULITE 2000*,
Dimension Vista, Dimension EXL (T4 extended to RxL, Xpand)• Age Groups: Infants (1–23 mo), children(2–12 yr), adolescents (13–20 yr)• IFU updates with claims after FDA 510K clearance
* data not yet available
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Study Design
Study Design:
• 8 collection sites used across the US to collectsamples
• Samples were aliquoted and shipped frozen toone laboratory for testing
• Testing was conducted in batch, and run insingleton on the Siemens platforms listedpreviously
• Samples were tested with handling conditionsrecommended for each assay as per the IFU
• Sample size total per platform:• ADVIA Centaur: 391• Dimension Vista: 422• Dimension EXL: 408
Statistical Approach:
• For the 2-12 yr and 13-20 yr old age groups, thelower and upper reference limits were establishedas the 2.5th and 97.5th percentiles of the test resultdistribution
• For the infants, the lower and upper reference limitswere estimated as the 2.5th and 97.5th percentilesof the distribution produced by the robust method
• For the child and adolescent subgroups, where>120 subject results were available, a non-parametric approach was used (CLSI guideline)
• For the infant subgroup where <120 subject resultswere available, a robust approach by Horn andPesce were used
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ResultsADVIA Centaur Systems (Global Release)
AgeGroup
SampleSize TSH3-UL* FT4 FT3 T4 T3
µIU/mL (mIU/L) ng/dL pmol/L pg/mL pmol/L µg/dL nmol/L ng/mL nmol/L
Infants(1-23 mo) 72 0.87-6.15 0.94-1.44 12-19 3.28-5.19 5.1-8.0 6.03-13.18 78-170 1.17-2.39 1.8-3.7
Children(2-12 yr) 190 0.67-4.16 0.86-1.40 11-18 3.34-4.80 5.1-7.4 5.50-12.10 71-156 1.05-2.07 1.6-3.2
Adolescents(13-20 yr) 129 0.48-4.17 0.83-1.43 11-18 3.04-4.65 4.7-7.2 5.50-11.10 71-143 0.86-1.92 1.3-3.0
ADVIA Centaur Pediatric Reference Intervals
* The sample size for TSH3UL is the following; infants-94, children-198 and adolescents-150
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Case 1
27-year-old female complaining of fatigue, weight gain, and weaknesswho is trying to get pregnant. Most recent pregnancy test was negative.
Is this individual at risk for thyroid dysfunction?
Should thyroid testing be performed?
What is the first test that should be run?
What other tests should be considered?
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Case 1
Is this patient at risk for thyroid dysfunction?Yes, her symptoms are consistent with hypothyroidism
Should thyroid testing be performed?Yes
What is the first test that should be run?A sensitive TSH test
What other tests should be considered?Free T4, total T4, anti-TPO
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Case 1
What is the likely diagnosis?Hypothyroidism(Hashimoto’s disease)
Test Value
TSH High
Free T4 Low
Free T3 Normal
Anti-TPO Present
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Case 2
A 45-year-old female complains of nervousness, irritability, and palpitationsand difficulty sleeping. She thinks that she might be entering menopause.Her thyroid gland is enlarged but no distinct nodules apparent.
Is this individual at risk for thyroid dysfunction?
Should thyroid testing be performed?
What is the first test that should be run?
What other tests should be considered?
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Case 2
Is this patient at risk for thyroid dysfunction?Yes, her symptoms are consistent with hyperthyroidism
Should thyroid testing be performed?Yes
What is the first test that should be run?A sensitive TSH test
What other tests should be considered?Free T4, Total T4, TRAb, TSI, thyroid scan
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Case 2
What is the likely diagnosis?Hyperthyroidism(Graves’ disease)
Test Value
TSH Low
Free T4 High
Free T3 Normal
TSI Present
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Case 3
A 31-year-old female, mother of one, with a history 3 miscarriages anddifficulty getting pregnant is planning another pregnancy. She complains ofweight gain and decreased heat tolerance.
Is this individual at risk for thyroid dysfunction?
Should thyroid testing be performed?
What is the first test that should be run?
What other tests should be considered?
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Case 3
Is this patient at risk for thyroid dysfunction?Yes, her symptoms are consistent with thyroid dysfunction
Should thyroid testing be performed?Yes
What is the first test that should be run?A sensitive TSH test
What other tests should be considered?Free T4, TRAb, TSI, TPO
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Case 3
What is the likely diagnosis?Hyperthyroidism, T3
(Early Graves Disease)
Test Value
TSH High
Free T4 Normal
Free T3 High
TSI Present
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Case 4
47-year-old male found a painless lump in his throat while shaving and hasalso noticed increased fatigue for the past few weeks. He has no othercomplaints and is a well controlled type 1 diabetic. On physical examinationthe lump is in the left lobe of the thyroid gland.
Is this individual at risk for thyroid dysfunction?
Should thyroid testing be performed?
What is the first test that should be run?
What other tests should be considered?
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Case 4
Is this patient at risk for thyroid dysfunction?Yes, he has a nodule and is complaining of fatigue
Should thyroid testing be performed?Yes, the nodule will also require investigation
What is the first test that should be run?A sensitive TSH test
What other tests should be considered?Free T4, fine needle aspiration and biopsy, radiological studies
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• Linda C. Rogers, PhD, DABCC, FACBSenior Clinical Consultant
• Scientific & Clinical AffairsSiemens HealthcareMobile: (949) 421-9101
• E-mail:rogers.linda@siemens.com
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