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
 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 1
1. How would you characterize her
hypothyroidism?
2. What are the ramifications of pregnancy
to thyroid function/dysfunction?
 TSH

High Low

FT4 FT4 & FT3

High Low Low High

1° Hypothyroid Central 1° Thyrotoxicosis

Hypothyroid
If
2° thyrotoxicosis equivocal
TRH Stim. RAIU

•Endo consult
•FT3, rT3
•MRI, α-SU
MRI, etc.
TRH Stimulation test

A) 1° Hypothyroidism
B) Central Hypothyroidism
C) Euthyroid
D) 1° Thyrotoxicosis
 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
1. Thyroid Function
2. Iodine Kinetics
3. Thyroid Structure
4. FNA
5. Thyroid Antibodies
6. 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)

15%
T3 Protein* binding + 0.3% free T3
(10-20x less than T4)

Total T4 60-155 nM * TBG 75%

TBPA 15%
Total T3 0.7-2.1 nM Albumin 10%
T3RU/THBI 0.77-1.23
 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)

 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 1
1. How would you characterize her
hypothyroidism?
2. What are the ramifications of pregnancy
to thyroid function/dysfunction?
 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

 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 pregnant
Starting 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 & 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
 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 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 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
 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 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 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
  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 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 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 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 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
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)

15%
T3 Protein* binding + 0.3% free T3
(10-20x less than T4)
 T4 T3

Potency 1 10

Protein Bound 10-20 1

Half-Life 5-7d < 24h

Secreted by 100 ug/d 6 ug/d

thyroid
 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)
 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.”
 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)
 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
 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 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…”
 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 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 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”

 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
 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 4
 FNA of 3cm nodule on Right: benign
 Rx’s offered:
 RAI ablation versus thyroidectomy
 Patient chose Thyroidectomy
 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
 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
 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
 Physical Exam
 Thyroid Ultrasound
 Thyroid Scan
 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 U/S
Benign Malignant
Characteristics Characteristics
Regular border Irregular border
Halo (sonolucent rim) No Halo
Hyperechoic Hypoechoic
(more vascular)
Egg shell calcification Microcalcification

N/A Intranodular vascular spots

(color doppler)
 Thyroid Scan
Thyroid nodule: risk of malignancy 6.5%

only 5-10% of nodules

Cold nodule “Warm” Nodule Hot Nodule

16-20% malignant (indeterminant) Tc-99m < 5% malignant
5% malignant I123 < 1% malignant
 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%
 Thyroid Nodule
Palpable
>15mm Follow
U/S q1y

TSH
Low Normal Benign Clin suspicion
or High Low

Scan FNA Insufficient Repeat FNA

Sample +/- U/S guide
Not
Hot Hot Clin suspicion
Suspicious High
Malignant
(Follicular)
Rx Plummer’s
•Surgery Hemithyroidectomy
Total +
•RAI with quick section
Thyroidectomy

-
RAI Close
 Incidentaloma
(Size < 15mm) Thyroid Nodule
Hx of XRT exposure?
FHx of thyroid cancer?
Palpable
Malign features on U/S? >15mm Follow
Age < 20 or > 60?
Grave’s Disease? U/S q1y
Familial Adenomatosis Polyposis
TSH
No Yes Benign Clin suspicion
Low Normal
or High Low
Follow
U/S q1y ? Scan FNA Insufficient Repeat FNA
Sample +/- U/S guide
Not
Hot Hot Clin suspicion
Suspicious High
Malignant
(Follicular)
Rx Plummer’s
•Surgery Hemithyroidectomy
Total +
•RAI with quick section
Thyroidectomy

-
RAI Close