diagnosis of thyroid disorders
DESCRIPTION
Diagnosis of Thyroid Disorders. William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University www.drharper.ca . Case 1. 31 year old female Somalia Canada 3 years ago G2P1A0, 11 weeks pregnant Well except fatigue Hb 108 , ferritin 7 - PowerPoint PPT PresentationTRANSCRIPT
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Diagnosis of Thyroid DisordersDiagnosis of Thyroid Disorders
William Harper, MD, FRCPCEndocrinology & Metabolism
Assistant Professor of Medicine, McMaster University
www.drharper.ca
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Case 1Case 1
31 year old female Somalia Canada 3 years ago G2P1A0, 11 weeks pregnant Well except fatigue Hb 108, ferritin 7 TSH 0.2 mU/L, FT4 7 pM Started on LT4 0.05 TSH < 0.01 mU/L
FT4 12 pM, FT3 2.1 pM
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Case 1Case 1
1. How would you characterize her hypothyroidism?
2. What are the ramifications of pregnancy to thyroid function/dysfunction?
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TSH
LowHigh
FT4 FT4 & FT3
Low
1° Hypothyroid
Low
Central Hypothyroid
TRH Stim.
Ifequivocal
MRI, etc.
High
1° Thyrotoxicosis
High
2° thyrotoxicosis
•Endo consult•FT3, rT3•MRI, α-SU
RAIU
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TRH Stimulation testTRH Stimulation test
A) 1° HypothyroidismB) Central HypothyroidismC) EuthyroidD) 1° Thyrotoxicosis
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Case 1Case 1 GH, IGF-1 normal LH, FSH, E2, progesterone, PRL normal for
pregnancy 8 AM cortisol 345, short ACTH test normal MRI: normal pituitary TGAB, TPOAB negative LT4 increased until FT4 in hi-normal range Normal pregnancy, delivery, baby, lactation Considering TRH stim once done breast-feeding
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Thyroid TestsThyroid Tests
1. Thyroid Function2. Iodine Kinetics3. Thyroid Structure4. FNA5. Thyroid Antibodies6. Thyroglobulin
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T4
T385% (peripheral conversion)
15%
Protein* binding + 0.03% free T4
Protein* binding + 0.3% free T3 (10-20x less than T4)
Normal Daily Thyroid Secretion Rate:T4 = 100 ug/day
T3 = 6 ug/day( ratio T4:T3 = 14:1 )
Total T4 60-155 nMTotal T3 0.7-2.1 nMT3RU/THBI 0.77-1.23
TBG 75%TBPA 15%Albumin 10%
*
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Thyroid Function TestsThyroid Function Tests
TSH 0.4 –5.0 mU/L
Free T4 (thyroxine) 9.1 – 23.8 pMFree T3 (triiodothyronine) 2.23-5.3 pM
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TSH AssayTSH Assay(0.4-5 mU/L)(0.4-5 mU/L)
Early RIA < 1.0 mU/L Thyrotoxicosis / 2º hypothyroidism
– Unable to detect lower range of normal
Monoclonal SEN < 0.1 mU/LSuper SEN < 0.01 mU/L
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Case 1Case 1
1. How would you characterize her hypothyroidism?
2. What are the ramifications of pregnancy to thyroid function/dysfunction?
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Thyroid & Pregnancy: Normal Thyroid & Pregnancy: Normal PhysiologyPhysiology
Increased estrogen increased TBG Higher total T4, T3 (normal FT4, FT3 if thyroid gland
working properly) hCG peak end of 1st trimester, weak TSH agonist so may
cause slight goitre Fetal thyroid starts working at 11 wks T4 & T3 do NOT cross placenta (or do so minimally) Do cross placenta: PTU, MTZ, TSH-R Ab (stim or block) MTZ aplasia cutis scalp defects
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Thyroid & Pregnancy: HypothyroidismThyroid & Pregnancy: Hypothyroidism
Will need ~ 25% increase in LT4 during pregnancy due to increased TBG levels
Risks: increased spont abort, HTN, preterm pregnancy, 7 IQ points for fetus (NEJM, 341(8):549-555, Aug 31, 2001)
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LT4 dose adjustment in LT4 dose adjustment in Pregnancy:Pregnancy:Need TSH at baseline & q2mos while pregnantNeed TSH at baseline & q2mos while pregnantStarting LT4: 2 ug/kg/d and check TSH q4wk until euthythyroidStarting LT4: 2 ug/kg/d and check TSH q4wk until euthythyroid
TSH Dose Adjustment
TSH increased but < 10 Increase dose by 50 ug/d
TSH 10-20 Increase dose by 50-75 ug/d
TSH > 20 Increase dose by 100 ug/d
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Thyrotoxicosis & PregnancyThyrotoxicosis & Pregnancy
Risks: fetal anomalies, spont abort, preterm labor, fetal hyperthyoridism, thyroid storm in labor
No RAI ever Rx options: ATD or 2nd trimester thyroidectomy PTU drug of choice (avoid MTZ due to scalp
defects) Aim to keep FT4 levels in hi normal range OK to breast feed on PTU as does not go into
breast milk
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Postpartum ThyroiditisPostpartum Thyroiditis
5% (3-16%) postpartum women (25% T1DM) Up to 1 year postpartum (most 1-4 months) Lymphocytic infiltration (Hashimoto’s) Postpartum Exacerbation of all autoimmune dx 25-50% persistant hypothyroidism Small, diffuse, nontender goitre Transiently thyrotoxic Hypothyroid
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Postpartum ThyroiditisPostpartum Thyroiditis
Rx: Hyperthyroid symptoms: atenolol 25-50 mg od Hypothyroid symptoms: LT4 50-100 ug/d to
start• Adjust LT4 dose for symptoms and normalization of
TSH• Consider withdrawal at 6-9 months (25-50% persistent hypothyroid, hi-risk recur future
preg)
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Postpartum & ThyroidPostpartum & Thyroid Postpartum depression
When studied, no association between postpartum depression/thyroiditis
Overlapping symtoms, R/O thyroid before start antidepressents
Screening for Postpartum ThyroiditisHOW: TSH q3mos from 1 mos to 1 year postpartum?WHO:
– Symptoms of thyroid dysfn.– Goitre– T1DM– Postpartum thyroiditis with prior pregnancy
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Case 2Case 2 47 year old female Concerned about weight gain over past 15 years (15 lbs).
Otherwise asymptomatic BMI 25, Thyroid: 40 gm, rubbery firm. TSH 6.7 mU/L, FT4 13 pM, FT3 2.5 pM FHx: mother, sister – both on LT4 Medications: “Thyrosol” (health store) Wondering about hypothyroidism causing her weight gain Read on internet about “Wilson’s Disease”
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Case 2Case 2
1. When to treat “Subclinical” thyroid dysfunction?2. Naturopathic thyroid remedies3. Hypothryoidism Rx other than Levothyroxine4. What is Wilson’s Thyroid Disease?
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Subclincal HypothyroidismSubclincal Hypothyroidism TSH, normal FT4 Most asymptomatic & don’t need Rx (monitor TSH q2-5y) Rx Indications:
– Increased risk of progression TSH > 10, Female > 50 y.o. Anti-TPO Ab titre > 1:100,000 ? Goitre present ?
– Dyslipidemia? Total cholesterol (TC) 6-8% if TSH > 10 and TC > 6.2 nM
– Symptoms?– Pregnancy, Infertility, Ovulatory Dysfn.
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Subclinical HyperthyroidismSubclinical Hyperthyroidism TSH, Normal FT4 and FT3 Progression to overt hyperthyroidism low:
Men 0% per year Women 1.5% per year TMNG or toxic adenoma present 5% per year
Indications to Rx: Any cardiac disease (CAD, AFIB, etc.) Age > 60 (10 year risk AFIB 32%, 10% if normal TSH) TMNG or toxic adenoma Osteoporosis
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Case 2Case 2
1. When to treat “Subclinical” thyroid dysfunction?2. Naturopathic thyroid remedies (Thyrosol)3. Hypothryoidism Rx other than Levothyroxine4. What is Wilson’s Thyroid Disease?
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Hashimoto’s DiseaseHashimoto’s DiseaseMost common cause of hypothyroidism in
North America (not idodine defeciency!)Autoimmunelymphocytic thyroiditisFemales > Males, Runs in FamiliesAntithyroid antibodies:
Thyroglobulin Ab Microsomal Ab TSH-R Ab (block)
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Hashimoto’s DiseaseHashimoto’s DiseaseTreatment:
Thyroid Hormone Replacement Levothyroxine (T4) T3?, T4/T3 combo?, dessicated thyroid?
No benefit to giving iodine! In fact, iodine may decrease hormone production Wolff-Chaikoff effect (lack of escape)
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Case 2Case 2
1. When to treat “Subclinical” thyroid dysfunction?2. Naturopathic thyroid remedies3. Hypothryoidism Rx other than Levothyroxine4. What is Wilson’s Thyroid Disease?
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Treatment of Treatment of HypothyroidismHypothyroidism
Iodine only if iodine deficiency is the cause Rare in North America!
Replacement thyroid hormone medication: T4? T3? T4 + T3 Mixture? Thyroid Hormone from “natural sources” ?
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T4
T385% (peripheral conversion)
15%
Protein* binding + 0.03% free T4
Protein* binding + 0.3% free T3 (10-20x less than T4)
Normal Daily Thyroid Secretion Rate:T4 = 100 ug/day
T3 = 6 ug/day( ratio T4:T3 = 14:1 )
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T4 T3
Potency 1 10
Protein Bound 10-20 1
Half-Life 5-7d < 24h
Secreted by thyroid
100 ug/d 6 ug/d
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Levothyroxine (T4)Levothyroxine (T4) Synthroid (Abbott), Eltroxin (GSK) Synthetically made 50 ug white pill no dye (hypoallergenic) Most commonly prescribed treatment for
hypothyroidism No T3 (but 85% of T3 comes from T4 conversion) All patients made euthyroid biochemically Most (but not all) patients feel normal
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Levothyroxine (T4)Levothyroxine (T4)Average dose 1.6 ug/kgAge > 50-60 or cardiac disease: must start
at a low dose (25 ug/d)Recheck thyroid hormone levels every 4-6
weeks after a dose changeAim for a normal TSH level
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““I still don’t feel normal on Synthroid I still don’t feel normal on Synthroid even though my blood tests are even though my blood tests are
normal.”normal.”Free T4, Free T3
wide range of normalTSH (0.4 –5.0 mU/L)
Narrow range of normal, but still a range! Adjust dose for a lower TSH still in the normal
range?Tissue levels versus circulating levels?
No human studies Rodents: High T4 and normal T3 tissue levels
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Liothyronine (T3)Liothyronine (T3)Cytomel (Theramed)Shorter half-life
Fluctuating levels (i.e. need a slow-release pill) Twice daily dosing often needed
10x more potent: palpitations & other cardiac side effects
High T3 levels, low T4 levels (not physiologic either!)
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T3/T4 LiotrixT3/T4 LiotrixThyrolarCombo pill of T3 and T4Ratio of T4:T3 = 4:1 (not 14:1)T3 still not slow releaseFew small studies showing benefit
1999 NEJM study 33 patients Benefit: mood & cognitive function
Not available in Canada
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Desiccated Thyroid Desiccated Thyroid (Armour)(Armour)
Desiccated powder derived from thyroids of slaughtered pigs or cows
Vegetarian? Mad Cow Disease?
Contains T4 and T3 Still no slow-release of T3 Ratio of T4:T3
Variable Still not physiologic, often too high in T3 (T4:T3 = 3:1)
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““In an ideal world…”In an ideal world…”Mixed compound with T4:T3 = 14:1T3 component slow release formulationResultant:
Normal circulating TSH, FT4, FT3 Normal tissue levels of T4 and T3
Good, large studies (RCTs) demonstrating clear benefit over T4 alone
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Case 2Case 2
1. When to treat “Subclinical” thyroid dysfunction?2. Naturopathic thyroid remedies3. Hypothryoidism Rx other than Levothyroxine4. What is Wilson’s Thyroid Disease?
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““Wilson’s Syndrome”Wilson’s Syndrome”
Wilson’s disease: copper toxicity liver failure “Wilson’s Syndrome”
Dr. E. D. Wilson “discovered” this condition and named it after himself in late 1980’s
Decreased body temperature (low normal range) Hypothyroid symptoms (nonspecific) Normal thyroid function tests “Impaired T4 T3 conversion” “Build up of reverse T3” Treat with “Wilson’s T3-therapy” (presumably T3)
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Sick Euthyroid Syndrome, not Wilson’s syndrome!
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““Wilson’s Syndrome”Wilson’s Syndrome”
No scientific evidence that this condition exists No randomized trials proving safety or any benefit
of giving people T3 when their thyroid hormone levels are normal
This condition not endorsed by: Canadain Society of Endocrinology and Metabolism (CSEM) American Thyroid Association (ATA) Endocrine Society
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Case 4Case 429 year old female, engaged to be marriedT1DMThyroid U/S:
2.9 cm R lower pole 2.0 cm L lower pole, Many others ranging from 0.5-1.5 cm
TSH < 0.05 mU/L, FT4 19 pM, FT3 6.9 pMRAIU/Scan: 45% RAIU, hot nodule on Left
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Case 4Case 4
FNA of 3cm nodule on Right: benignRx’s offered:
RAI ablation versus thyroidectomyPatient chose Thyroidectomy
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RAIURAIU Oral dose of I131 5 uCi (or I123 200 uCi but more $) Measure neck counts @ 24h (+/- 4h if suspect high
turnover) RAIU = neck counts – bkgd (thigh counts) x 100 pill counts - bkgd
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RAIURAIU Normal 4h RAIU = 5-15 % 24h RAIU:
>25% Hyperthyroid20-25% Equivocal (check TSH)9-20% Normal5-9% Equivocal (check TSH)<5% Hypothyroid
Dependent on dietary iodine intake! Must be: not pregnant! (ß-hCG), no ATD x 7d, no LT4 x 4d, no large
doses of iodine or radiocontrast for 2 wk (prefer 4-6 wk)
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Thyrotoxicosis TreatmentThyrotoxicosis TreatmentBeta-blockers (hyperadrenergic symptoms)Hyperthyroidism:
Anti-thyroid Drugs– Propylthiouracil (PTU), Methimazole
Radioiodine Ablation Surgical Thyroidectomy
Thyroiditis: ASA, NSAIDS, +/- corticosteroids
Iodine (high doses Wolff Chaikoff effect)
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Thyroid StructureThyroid Structure
Physical ExamThyroid UltrasoundThyroid Scan
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Thyroid nodulesThyroid nodules U/S more sensitive than P.E., particularly for nodules that
are < 1 cm or located posteriorly in the gland. U/S also more SEN than thyroid scan U/S too Sensitive?
Thyroid Incidentaloma (Carotid duplex, etc.)
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Thyroid U/SThyroid U/SBenign
CharacteristicsMalignant
Characteristics
Regular borderHalo (sonolucent rim)
Irregular borderNo Halo
Hyperechoic Hypoechoic(more vascular)
Egg shell calcification Microcalcification
N/A Intranodular vascular spots(color doppler)
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Thyroid ScanThyroid Scan
Thyroid nodule: risk of malignancy 6.5%
Cold nodule16-20% malignant
“Warm” Nodule (indeterminant) 5% malignant
Hot NoduleTc-99m < 5% malignantI123 < 1% malignant
only 5-10% of nodules
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Fine Needle Aspiration (FNA)Fine Needle Aspiration (FNA)
25G Needle, 10cc syringeDone in Office+/- Local3-5 passesSEN 95-99% (False Negative rate 1-5%)SPEC > 95%
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Thyroid NodulePalpable>15mm
TSH
Low Normalor High
Scan
HotNotHot
FNA
MalignantSuspicious(Follicular)
Benign
InsufficientSample
Repeat FNA+/- U/S guide
Clin suspicionLow
Clin suspicionHigh
TotalThyroidectomy
RAI
Hemithyroidectomywith quick section+
-Close
Rx Plummer’s•Surgery•RAI
FollowU/S q1y
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Thyroid NodulePalpable>15mm
Incidentaloma(Size < 15mm)
Hx of XRT exposure?FHx of thyroid cancer?
Malign features on U/S?Age < 20 or > 60?Grave’s Disease?
Familial Adenomatosis Polyposis
No
FollowU/S q1y ?
YesTSH
Low Normalor High
Scan
HotNotHot
FNA
MalignantSuspicious(Follicular)
Benign
InsufficientSample
Repeat FNA+/- U/S guide
Clin suspicionLow
Clin suspicionHigh
TotalThyroidectomy
RAI
Hemithyroidectomywith quick section+
-Close
Rx Plummer’s•Surgery•RAI
FollowU/S q1y