Diagnosis of Thyroid DisordersDiagnosis of Thyroid Disorders

William Harper, MD, FRCPC

Endocrinology & Metabolism

Assistant Professor of Medicine, McMaster University

www.drharper.ca

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

Case 1Case 1

1. How would you characterize her hypothyroidism?

2. What are the ramifications of pregnancy to thyroid function/dysfunction?

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

TRH Stimulation testTRH Stimulation test

A) 1° HypothyroidismB) Central HypothyroidismC) EuthyroidD) 1° Thyrotoxicosis

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

Thyroid TestsThyroid Tests

1. Thyroid Function

2. Iodine Kinetics

3. Thyroid Structure

4. FNA

5. Thyroid Antibodies

6. Thyroglobulin

T4

T3

85% (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/dayT3 = 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%

*

Thyroid Function TestsThyroid Function Tests

TSH 0.4 –5.0 mU/L

Free T4 (thyroxine) 9.1 – 23.8 pM

Free T3 (triiodothyronine) 2.23-5.3 pM

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

Case 1Case 1

1. How would you characterize her hypothyroidism?

2. What are the ramifications of pregnancy to thyroid function/dysfunction?

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

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)

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

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

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

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)

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

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”

Case 2Case 2

1. When to treat “Subclinical” thyroid dysfunction?

2. Naturopathic thyroid remedies

3. Hypothryoidism Rx other than Levothyroxine

4. What is Wilson’s Thyroid Disease?

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.

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

Case 2Case 2

1. When to treat “Subclinical” thyroid dysfunction?

2. Naturopathic thyroid remedies (Thyrosol)

3. Hypothryoidism Rx other than Levothyroxine

4. What is Wilson’s Thyroid Disease?

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)

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)

Case 2Case 2

1. When to treat “Subclinical” thyroid dysfunction?

2. Naturopathic thyroid remedies

3. Hypothryoidism Rx other than Levothyroxine

4. What is Wilson’s Thyroid Disease?

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” ?

T4

T3

85% (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/dayT3 = 6 ug/day

( ratio T4:T3 = 14:1 )

T4 T3

Potency 1 10

Protein Bound 10-20 1

Half-Life 5-7d < 24h

Secreted by thyroid

100 ug/d 6 ug/d

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

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

““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 normal

TSH (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

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!)

T3/T4 LiotrixT3/T4 Liotrix

ThyrolarCombo 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

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)

““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

Case 2Case 2

1. When to treat “Subclinical” thyroid dysfunction?

2. Naturopathic thyroid remedies

3. Hypothryoidism Rx other than Levothyroxine

4. What is Wilson’s Thyroid Disease?

““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)

Sick Euthyroid Syndrome, not Wilson’s syndrome!

““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

Case 4Case 4

29 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

Case 4Case 4

FNA of 3cm nodule on Right: benignRx’s offered:

RAI ablation versus thyroidectomy

Patient chose Thyroidectomy

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

RAIURAIU

Normal 4h RAIU = 5-15 % 24h RAIU:

>25% Hyperthyroid

20-25% Equivocal (check TSH)

9-20% Normal

5-9% 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)

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)

Thyroid StructureThyroid Structure

Physical ExamThyroid UltrasoundThyroid Scan

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.)

Thyroid U/SThyroid U/SBenign

Characteristics

Malignant Characteristics

Regular border

Halo (sonolucent rim)

Irregular border

No Halo

Hyperechoic Hypoechoic

(more vascular)

Egg shell calcification Microcalcification

N/A Intranodular vascular spots

(color doppler)

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

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%

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

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