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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?
slide5

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
slide9

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)
slide17
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” ?
slide33

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)
  • 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
  • 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)
  • 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 = 14:1
  • 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
  • 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”
  • 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”
  • 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
  • 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
  • FNA of 3cm nodule on Right: benign
  • Rx’s offered:
      • RAI ablation versus thyroidectomy
  • Patient chose Thyroidectomy
slide49
RAIU
  • 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

slide50
RAIU
  • 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
  • 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
  • Physical Exam
  • Thyroid Ultrasound
  • Thyroid Scan
thyroid nodules
Thyroid 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 scan
Thyroid Scan

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)
  • 25G Needle, 10cc syringe
  • Done in Office
  • +/- Local
  • 3-5 passes
  • SEN 95-99% (False Negative rate 1-5%)
  • SPEC > 95%
slide57

Thyroid Nodule

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

slide58

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

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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