thyroid talk-fmd rds

8/7/2019 Thyroid Talk-FMD Rds

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Case 1Case 131 year old femaleSomalia Canada 3 years agoG2P 1 A0, 11 weeks pregnantWell except fatigueHb 1 08, ferritin 7

TSH 0.2 mU/L, FT4 7 pMStarted on LT4 0.05 TSH < 0.0 1 mU/L

FT4 1 2 pM, FT 3 2.1 pM



Case 1Case 11 . How would you characterize her

hypothyroidism?2. What are the ramifications of pregnancy to

thyroid function/dysfunction?



TSH

LowHigh

FT4 FT4 & FT 3

Low

1° Hypothyroid

Low

CentralHypothyroid

TRH Stim.

If

equivocal

MRI, etc.

High

1° Thyrotoxicosis

High

2° thyrotoxicosis

�Endo consult�FT 3 , rT3

�MRI, -SU

RAIU



TRH Stimulation testTRH Stimulation test

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



Case 1Case 1GH, IGF- 1 normalLH, FSH, E2, progesterone, PRL normal for

pregnancy8 AM cortisol 3 45, short ACTH test normalMRI: normal pituitaryTGAB, TPOAB negativeLT4 increased until FT4 in hi-normal rangeNormal pregnancy, delivery, baby, lactationConsidering TRH stim once done breast-feeding



Thyroid TestsThyroid Tests1 . Thyroid Function2. Iodine Kinetics3 . Thyroid Structure4. FNA

5. Thyroid Antibodies6. Thyroglobulin



T4

T3

85% (peripheral conversion)

1 5%

Protein* binding + 0.0 3 % free T4

Protein* binding + 0. 3 % free T 3 (1 0-20x less than T4)

Normal Daily Thyroid Secretion Rate:T4 = 1 00 ug/day

T3

= 6 ug/day( ratio T4:T 3 = 1 4:1 )

Total T4 60- 1 55 nMTotal T 3 0.7-2. 1 nMT3 RU/THBI 0.77- 1 .23

TBG 75%TBPA 1 5%Albumin 1 0%

*



Thyroid Function TestsThyroid Function Tests

TSH 0.4 ±5.0 mU/LFree T4 (thyroxine) 9. 1 ± 23 .8 pMFree T 3 (triiodothyronine) 2.2 3 -5.3 pM



TSH AssayTSH Assay(0.4(0.4--5 mU/L)5 mU/L)

Early RIA < 1 .0 mU/LThyrotoxicosis / 2º hypothyroidism

± Unable to detect lower range of normal

Monoclonal SEN < 0. 1 mU/L

Super SEN < 0.0 1 mU/L



Case 1Case 11 . How would you characterize her

hypothyroidism?2. What are the ramifications of pregnancy to

thyroid function/dysfunction?



Thyroid & Pregnancy: NormalThyroid & Pregnancy: Normal

PhysiologyPhysiologyIncreased estrogen increased TBGHigher total T4, T 3 (normal FT4, FT 3 if thyroid gland

working properly)hCG peak end of 1 st trimester, weak TSH agonist so maycause slight goitreFetal thyroid starts working at 11 wks

T4 & T 3 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 duringpregnancy due to increased TBG levels

Risks: increased spont abort, HTN, pretermpregnancy, 7 IQ points for fetus (NEJM,3 41 (8):549-555, Aug 31 , 200 1 )



L T4 dose adjustment inL T4 dose adjustment inPregnancy:Pregnancy:N eed T S H at baseline & q2mos while pregnantN eed T S H at baseline & q2mos while pregnantStarting L T 4: 2 ug/kg/d and check T S H q4wk until euthythyroidStarting L T 4: 2 ug/kg/d and check T S H q4wk until euthythyroid

TSH Dose Adjustment

TSH increased but < 1 0 Increase dose by 50 ug/d

TSH 1 0-20 Increase dose by 50-75 ug/d

TSH > 20 Increase dose by 1 00 ug/d



Thyrotoxicosis & PregnancyThyrotoxicosis & PregnancyRisks: fetal anomalies, spont abort, preterm labor,fetal hyperthyoridism, thyroid storm in labor

No RAI ever Rx options: ATD or 2 nd trimester thyroidectomyPTU drug of choice (avoid MTZ due to scalpdefects)

Aim to keep FT4 levels in hi normal rangeOK to breast feed on PTU as does not go intobreast milk



Postpartum

Thyroiditis

Postpartum

Thyroiditis

5% ( 3 -1 6%) postpartum women (25% T 1 DM)Up to 1 year postpartum (most 1 -4 months)Lymphocytic infiltration (Hashimoto¶s)Postpartum Exacerbation of all autoimmune dx25-50% persistant hypothyroidism

Small, diffuse, nontender goitreTransiently thyrotoxic Hypothyroid



Postpartum

Thyroiditis

Postpartum

Thyroiditis

Rx:Hyperthyroid symptoms: atenolol 25-50 mg od

Hypothyroid symptoms: LT4 50- 1 00 ug/d to startAdjust LT4 dose for symptoms and normalization of TSHConsider withdrawal at 6-9 months(25-50% persistent hypothyroid, hi-risk recur futurepreg)



Postpartum &

Thyroid

Postpartum &

Thyroid

Postpartum depressionWhen studied, no association between postpartumdepression/thyroiditisOverlapping symtoms, R/O thyroid before start antidepressents

Screening for Postpartum ThyroiditisHOW: TSH q 3 mos from 1 mos to 1 year postpartum?WHO:

± Symptoms of thyroid dysfn.± Goitre± T1 DM± Postpartum thyroiditis with prior pregnancy



Case 2Case 247 year old femaleConcerned about weight gain over past 1 5 years ( 1 5 lbs).

Otherwise asymptomaticBMI 25, Thyroid: 40 gm, rubbery firm.TSH 6.7 mU/L, FT4 13 pM, FT 3 2.5 pMFHx: mother, sister ± both on LT4

Medications: ³Thyrosol´ (health store)Wondering about hypothyroidism causing her weight gainRead on internet about ³Wilson¶s Disease´



Case 2Case 21 . When to treat ³Subclinical´ thyroid dysfunction?2. Naturopathic thyroid remedies3 . Hypothryoidism Rx other than Levothyroxine4. What is Wilson¶s Thyroid Disease?



Subclincal HypothyroidismSubclincal Hypothyroidismo TSH, normal FT4Most asymptomatic & don¶t need Rx (monitor TSH q2-5y)

Rx Indications:± Increased risk of progression

TSH > 1 0, Female > 50 y.o.Anti-TPO Ab titre > 1 :1 00,000 ?Goitre present ?

± Dyslipidemia?Total cholesterol (TC) q 6-8% if TSH > 1 0 and TC > 6.2 nM

± Symptoms?± Pregnancy, Infertility, Ovulatory Dysfn.



Subclinical HyperthyroidismSubclinical Hyperthyroidismq TSH, Normal FT4 and FT 3

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 ( 1 0 year risk AFIB 3 2%, 1 0% if normal TSH)TMNG or toxic adenomaOsteoporosis



Case 2Case 21 . When to treat ³Subclinical´ thyroid dysfunction?2. Naturopathic thyroid remedies (Thyrosol)3 . Hypothryoidism Rx other than Levothyroxine4. What is Wilson¶s Thyroid Disease?



Hashimoto¶s DiseaseHashimoto¶s DiseaseMost common cause of hypothyroidism inNorth America (not idodine defeciency!)

Autoimmunelymphocytic thyroiditisFemales > Males, Runs in FamiliesAntithyroid antibodies:

Thyroglobulin AbMicrosomal AbTSH-R Ab (block)



Hashimoto¶s DiseaseHashimoto¶s DiseaseTreatment:

Thyroid Hormone Replacement

Levothyroxine (T4)T3 ?, T4/T 3 combo?, dessicated thyroid?

No benefit to giving iodine!In fact, iodine may decrease hormone production

Wolff-Chaikoff effect (lack of escape)



T4

T3

85% (peripheral conversion)

1 5%

Protein* binding + 0.0 3 % free T4

Protein* binding + 0. 3 % free T 3 (1 0-20x less than T4)

Normal Daily Thyroid Secretion Rate:T4 = 1 00 ug/day

T3 = 6 ug/day( ratio T4:T 3 = 1 4:1 )



T4 T3

Potency 1 1 0

Protein Bound 1 0-20 1

Half-Life 5-7d < 24h

Secreted bythyroid

1 00 ug/d 6 ug/d



Levothyroxine (T4)

Levothyroxine (T4)

Synthroid (Abbott), Eltroxin (GSK)Synthetically made50 ug white pill no dye (hypoallergenic)Most commonly prescribed treatment for hypothyroidism

No T 3 (but 85% of T 3 comes from T4 conversion)All patients made euthyroid biochemicallyMost (but not all) patients feel normal



³I still don¶t feel normal on Synthroid³I still don¶t feel normal on Synthroideven though my blood tests areeven though my blood tests are

normal.´normal.´Free T4, Free T 3

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 normalrange?

Tissue levels versus circulating levels?No human studiesRodents: High T4 and normal T 3 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

1 0x more potent: palpitations & other cardiac side effectsHigh T 3 levels, low T4 levels (notphysiologic either!)



Desiccated ThyroidDesiccated Thyroid(Armour)(Armour)

Desiccated powder derived from thyroids of slaughtered pigs or cows

Vegetarian?Mad Cow Disease?

Contains T4 and T 3

Still no slow-release of T 3

Ratio of T4:T 3

VariableStill not physiologic, often too high in T 3 (T4:T 3 = 3 :1 )



³In an ideal world«´

³In an ideal world«´

Mixed compound with T4:T 3 = 1 4:1

T3 component slow release formulation

Resultant:Normal circulating TSH, FT4, FT 3

Normal tissue levels of T4 and T 3

Good, large studies (RCTs) demonstratingclear benefit over T4 alone



Sick Euthyroid Syndrome, not Wilson¶s syndrome!



³W ilson¶s Syndrome´³W ilson¶s Syndrome´

No scientific evidence that this condition existsNo randomized trials proving safety or any benefitof giving people T 3 when their thyroid hormonelevels are normalThis condition not endorsed by:

Canadain Society of Endocrinology and Metabolism (CSEM)American Thyroid Association (ATA)Endocrine Society



Case 4Case 429 year old female, engaged to be marriedT1 DMThyroid U/S:

2.9 cm R lower pole2.0 cm L lower pole,Many others ranging from 0.5- 1 .5 cm

TSH < 0.05 mU/L, FT4 1 9 pM, FT 3 6.9 pMRAIU/Scan: 45% RAIU, hot nodule on Left



Case 4Case 4FNA of 3 cm nodule on Right: benignRx¶s offered:

RAI ablation versus thyroidectomy

Patient chose Thyroidectomy



RAI URAI UOral dose of I

131

5 uCi (or I1

23

200 uCi but more $)Measure neck counts @ 24h (+/- 4h if suspect highturnover)RAIU = neck counts ± bkgd (thigh counts) x 1 00

pill counts - bkgd



R AIUR AIU

Normal 4h RAIU = 5- 1 5 %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 largedoses of iodine or radiocontrast for 2 wk (prefer 4-6 wk)



Thyrotoxicosis TreatmentThyrotoxicosis TreatmentBeta-blockers (hyperadrenergic symptoms)Hyperthyroidism:

Anti-thyroid Drugs

± Propylthiouracil (PTU), MethimazoleRadioiodine AblationSurgical Thyroidectomy

Thyroiditis:ASA, NSAIDS, +/- corticosteroids

Iodine (high doses Wolff Chaikoff effect)



T hyroid StructureT hyroid Structure

Physical ExamThyroid UltrasoundThyroid Scan



Thyroid nodulesThyroid nodules

U/S more sensitive than P.E., particularly for nodules thatare < 1 cm or located posteriorly in the gland.U/S also more SEN than thyroid scanU/S too Sensitive?

Thyroid Incidentaloma (Carotid duplex, etc.)



T hyroid U/ST hyroid U/SBenign

CharacteristicsMalignant

Characteristics

Regular border

Halo (sonolucent rim)

Irregular border

No HaloHyperechoic 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 nodule1 6-20% malignant

³Warm´ Nodule(indeterminant)5% malignant

Hot NoduleTc-99m < 5% malignantI1 23 < 1 % malignant

only 5- 1 0% of nodules



Fine Needle Aspiration (FNA)Fine Needle Aspiration (FNA)

25G Needle, 1 0cc syringeDone in Office+/- Local3 -5 passesSEN 95-99% (False Negative rate 1 -5%)SPEC > 95%



Thyroid NodulePalpable>1 5mm

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 q 1 y

Incidentaloma



Thyroid NodulePalpable>1 5mm

Incidentaloma(Size < 1 5mm)

Hx of XRT exposure?FHx of thyroid cancer?Malign features on U/S?

Age < 20 or > 60?Grave¶s Disease?

Familial Adenomatosis Polyposis

No

Follow

U/S q 1 y ?

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+

-

Rx Plummer¶s�Surgery�RAI

FollowU/S q 1 y

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