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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

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Diagnosis of thyroid disorders

Diagnosis of Thyroid Disorders

William Harper, MD, FRCPC

Endocrinology & Metabolism

Assistant Professor of Medicine, McMaster University

www.drharper.ca


Case 1
Case 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 11
Case 1

  • How would you characterize her hypothyroidism?

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


TSH

Low

High

FT4 & FT3

FT4

Low

Low

High

High

Central Hypothyroid

1° Thyrotoxicosis

1° Hypothyroid

If

equivocal

2° thyrotoxicosis

RAIU

TRH Stim.

  • Endo consult

  • FT3, rT3

  • MRI, α-SU

MRI, etc.


Trh stimulation test
TRH Stimulation test

A) 1° Hypothyroidism

B) Central Hypothyroidism

C) Euthyroid

D) 1° Thyrotoxicosis


Case 12
Case 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 tests
Thyroid Tests

  • Thyroid Function

  • Iodine Kinetics

  • Thyroid Structure

  • FNA

  • Thyroid Antibodies

  • Thyroglobulin


Normal Daily Thyroid Secretion Rate:

T4 = 100 ug/day

T3 = 6 ug/day

( ratio T4:T3 = 14:1 )

T4

Protein* binding + 0.03% free T4

85% (peripheral conversion)

T3

Protein* binding + 0.3% free T3

15%

(10-20x less than T4)

*

TBG 75%

TBPA 15%

Albumin 10%

Total T4 60-155 nM

Total T3 0.7-2.1 nM

T3RU/THBI 0.77-1.23


Thyroid function tests
Thyroid 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 assay 0 4 5 mu l
TSH Assay(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/L

  • Super SEN < 0.01 mU/L


  • Case 13
    Case 1

    • How would you characterize her hypothyroidism?

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


    Thyroid pregnancy normal physiology
    Thyroid & Pregnancy: Normal Physiology

    • 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 hypothyroidism
    Thyroid & 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 Pregnancy:Need TSH at baseline & q2mos while pregnantStarting LT4: 2 ug/kg/d and check TSH q4wk until euthythyroid


    Thyrotoxicosis pregnancy
    Thyrotoxicosis & 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 thyroiditis
    Postpartum 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 thyroiditis1
    Postpartum 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 thyroid
    Postpartum & Thyroid

    • Postpartum depression

      • When studied, no association between postpartum depression/thyroiditis

      • Overlapping symtoms, R/O thyroid before start antidepressents

  • Screening for Postpartum Thyroiditis

    HOW: TSH q3mos from 1 mos to 1 year postpartum?

    WHO:

    • Symptoms of thyroid dysfn.

    • Goitre

    • T1DM

    • Postpartum thyroiditis with prior pregnancy


  • Case 2
    Case 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 21
    Case 2

    • When to treat “Subclinical” thyroid dysfunction?

    • Naturopathic thyroid remedies

    • Hypothryoidism Rx other than Levothyroxine

    • What is Wilson’s Thyroid Disease?


    Subclincal hypothyroidism
    Subclincal 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 hyperthyroidism
    Subclinical 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 22
    Case 2

    • When to treat “Subclinical” thyroid dysfunction?

    • Naturopathic thyroid remedies (Thyrosol)

    • Hypothryoidism Rx other than Levothyroxine

    • What is Wilson’s Thyroid Disease?


    Hashimoto s disease
    Hashimoto’s Disease

    • Most common cause of hypothyroidism in North America (not idodine defeciency!)

    • Autoimmune

    • lymphocytic thyroiditis

    • Females > Males, Runs in Families

    • Antithyroid antibodies:

      • Thyroglobulin Ab

      • Microsomal Ab

      • TSH-R Ab (block)


    Hashimoto s disease1
    Hashimoto’s Disease

    • Treatment:

      • 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 23
    Case 2

    • When to treat “Subclinical” thyroid dysfunction?

    • Naturopathic thyroid remedies

    • Hypothryoidism Rx other than Levothyroxine

    • What is Wilson’s Thyroid Disease?


    Treatment of hypothyroidism
    Treatment of Hypothyroidism

    • 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” ?


  • Normal Daily Thyroid Secretion Rate:

    T4 = 100 ug/day

    T3 = 6 ug/day

    ( ratio T4:T3 = 14:1 )

    T4

    Protein* binding + 0.03% free T4

    85% (peripheral conversion)

    T3

    Protein* binding + 0.3% free T3

    15%

    (10-20x less than T4)


    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 t41
    Levothyroxine (T4)

    • Average dose 1.6 ug/kg

    • Age > 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 change

    • Aim for a normal TSH level


    I still don t feel normal on synthroid even though my blood tests are normal
    “I still don’t feel normal on Synthroid even though my blood tests are 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) blood tests are normal.”

    • 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 liotrix
    T3/T4 Liotrix blood tests are normal.”

    • Thyrolar

    • Combo pill of T3 and T4

    • Ratio of T4:T3 = 4:1 (not 14:1)

    • T3 still not slow release

    • Few small studies showing benefit

      • 1999 NEJM study 33 patients

      • Benefit: mood & cognitive function

  • Not available in Canada


  • Desiccated thyroid armour
    Desiccated Thyroid (Armour) blood tests are normal.”

    • 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…” blood tests are normal.”

    • Mixed compound with T4:T3 = 14:1

    • T3 component slow release formulation

    • Resultant:

      • Normal circulating TSH, FT4, FT3

      • Normal tissue levels of T4 and T3

  • Good, large studies (RCTs) demonstrating clear benefit over T4 alone


  • Case 24
    Case 2 blood tests are normal.”

    • When to treat “Subclinical” thyroid dysfunction?

    • Naturopathic thyroid remedies

    • Hypothryoidism Rx other than Levothyroxine

    • What is Wilson’s Thyroid Disease?


    Wilson s syndrome
    “Wilson’s Syndrome” blood tests are normal.”

    • 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)



    Wilson s syndrome1
    “Wilson’s Syndrome” blood tests are normal.”

    • 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 4
    Case 4 blood tests are normal.”

    • 29 year old female, engaged to be married

    • T1DM

    • Thyroid 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 pM

  • RAIU/Scan: 45% RAIU, hot nodule on Left


  • Case 41
    Case 4 blood tests are normal.”

    • FNA of 3cm nodule on Right: benign

    • Rx’s offered:

      • RAI ablation versus thyroidectomy

  • Patient chose Thyroidectomy


  • RAIU blood tests are normal.”

    • 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


    RAIU blood tests are normal.”

    • 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 treatment
    Thyrotoxicosis Treatment blood tests are normal.”

    • Beta-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 structure
    Thyroid Structure blood tests are normal.”

    • Physical Exam

    • Thyroid Ultrasound

    • Thyroid Scan


    Thyroid nodules
    Thyroid nodules blood tests are normal.”

    • 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 s
    Thyroid U/S blood tests are normal.”


    Thyroid scan
    Thyroid Scan blood tests are normal.”

    Thyroid nodule: risk of malignancy 6.5%

    only 5-10% of nodules

    Cold nodule

    16-20% malignant

    Hot Nodule

    Tc-99m < 5% malignant

    I123 < 1% malignant

    “Warm” Nodule

    (indeterminant)

    5% malignant


    Fine needle aspiration fna
    Fine Needle Aspiration (FNA) blood tests are normal.”

    • 25G Needle, 10cc syringe

    • Done in Office

    • +/- Local

    • 3-5 passes

    • SEN 95-99% (False Negative rate 1-5%)

    • SPEC > 95%


    Thyroid Nodule blood tests are normal.”

    Palpable

    >15mm

    Follow

    U/S q1y

    TSH

    Benign

    Clin suspicion

    Low

    Low

    Normal

    or High

    Scan

    FNA

    Insufficient

    Sample

    Repeat FNA

    +/- U/S guide

    Not

    Hot

    Hot

    Clin suspicion

    High

    Suspicious

    (Follicular)

    Malignant

    • Rx Plummer’s

    • Surgery

    • RAI

    Hemithyroidectomy

    with quick section

    Total

    Thyroidectomy

    +

    -

    RAI

    Close


    Incidentaloma blood tests are normal.”

    (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

    Thyroid Nodule

    Palpable

    >15mm

    Follow

    U/S q1y

    TSH

    No

    Yes

    Benign

    Clin suspicion

    Low

    Low

    Normal

    or High

    Follow

    U/S q1y ?

    Scan

    FNA

    Insufficient

    Sample

    Repeat FNA

    +/- U/S guide

    Not

    Hot

    Hot

    Clin suspicion

    High

    Suspicious

    (Follicular)

    Malignant

    • Rx Plummer’s

    • Surgery

    • RAI

    Hemithyroidectomy

    with quick section

    Total

    Thyroidectomy

    +

    -

    RAI

    Close


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