Diagnosis of Thyroid Disorders
William Harper, MD, FRCPC
Endocrinology & Metabolism
Assistant Professor of Medicine, McMaster University
www.drharper.ca
Case 1
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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.
2.
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
1° Hypothyroid
2° thyrotoxicosis
Central
1° Thyrotoxicosis
Hypothyroid
If
equivocal
TRH Stim.
•Endo consult
•FT3, rT3
•MRI, α-SU
High
MRI, etc.
RAIU
TRH Stimulation test
A) 1° Hypothyroidism
B) Central Hypothyroidism
C) Euthyroid
D) 1° Thyrotoxicosis
Case 1
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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
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6.
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
Protein* binding
+ 0.3% free T3
85% (peripheral conversion)
15%
T3
(10-20x less than T4)
Total T4
Total T3
T3RU/THBI
60-155 nM
0.7-2.1 nM
0.77-1.23
* TBG
75%
TBPA
15%
Albumin 10%
Thyroid Function Tests
TSH
Free T4 (thyroxine)
Free T3 (triiodothyronine)
0.4 –5.0 mU/L
9.1 – 23.8 pM
2.23-5.3 pM
TSH Assay
(0.4-5 mU/L)
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Early RIA < 1.0 mU/L
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Thyrotoxicosis / 2º hypothyroidism
– Unable to detect lower range of normal
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Monoclonal SEN < 0.1 mU/L
 Super SEN < 0.01 mU/L
Case 1
1.
2.
How would you characterize her
hypothyroidism?
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
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Thyroid & Pregnancy: Hypothyroidism
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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
TSH > 20
Increase dose by 50-75 ug/d
Increase dose by 100 ug/d
Thyrotoxicosis & Pregnancy
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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
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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
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Rx:
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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
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Postpartum depression
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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:
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Symptoms of thyroid dysfn.
Goitre
T1DM
Postpartum thyroiditis with prior pregnancy
Case 2
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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
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4.
When to treat “Subclinical” thyroid dysfunction?
Naturopathic thyroid remedies
Hypothryoidism Rx other than Levothyroxine
What is Wilson’s Thyroid Disease?
Subclincal Hypothyroidism
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 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
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 TSH, Normal FT4 and FT3
Progression to overt hyperthyroidism low:
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Men 0% per year
Women 1.5% per year
TMNG or toxic adenoma present 5% per year
Indications to Rx:
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Any cardiac disease (CAD, AFIB, etc.)
Age > 60 (10 year risk AFIB 32%, 10% if normal TSH)
TMNG or toxic adenoma
Osteoporosis
Case 2
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4.
When to treat “Subclinical” thyroid dysfunction?
Naturopathic thyroid remedies (Thyrosol)
Hypothryoidism Rx other than Levothyroxine
What is Wilson’s Thyroid Disease?
Hashimoto’s Disease
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Most common cause of hypothyroidism in
North America (not idodine defeciency!)
 Autoimmune
 lymphocytic thyroiditis
 Females > Males, Runs in Families
 Antithyroid antibodies:
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Thyroglobulin Ab
Microsomal Ab
TSH-R Ab (block)
Hashimoto’s Disease
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Treatment:
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Thyroid Hormone Replacement
Levothyroxine (T4)
T3?, T4/T3 combo?, dessicated thyroid?
No benefit to giving iodine!
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In fact, iodine may decrease hormone production
Wolff-Chaikoff effect (lack of escape)
Case 2
1.
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3.
4.
When to treat “Subclinical” thyroid dysfunction?
Naturopathic thyroid remedies
Hypothryoidism Rx other than Levothyroxine
What is Wilson’s Thyroid Disease?
Treatment of
Hypothyroidism
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Iodine only if iodine deficiency is the cause
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Rare in North America!
Replacement thyroid hormone medication:
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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
Protein* binding
+ 0.3% free T3
85% (peripheral conversion)
15%
T3
(10-20x less than T4)
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)
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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)
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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
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TSH (0.4 –5.0 mU/L)
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wide range of normal
Narrow range of normal, but still a range!
Adjust dose for a lower TSH still in the normal
range?
Tissue levels versus circulating levels?
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No human studies
Rodents: High T4 and normal T3 tissue levels
Liothyronine (T3)
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Cytomel (Theramed)
 Shorter half-life
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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
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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
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1999 NEJM study 33 patients
Benefit: mood & cognitive function
Not available in Canada
Desiccated Thyroid
(Armour)
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Desiccated powder derived from thyroids of
slaughtered pigs or cows
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Vegetarian?
Mad Cow Disease?
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Contains T4 and T3
 Still no slow-release of T3
 Ratio of T4:T3
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Variable
Still not physiologic, often too high in T3 (T4:T3 = 3:1)
“In an ideal world…”
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Mixed compound with T4:T3 = 14:1
 T3 component slow release formulation
 Resultant:
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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.
2.
3.
4.
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 disease: copper toxicity  liver failure
 “Wilson’s Syndrome”
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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”
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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:
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Canadain Society of Endocrinology and Metabolism (CSEM)
American Thyroid Association (ATA)
Endocrine Society
Case 4
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29 year old female, engaged to be married
 T1DM
 Thyroid U/S:
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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
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FNA of 3cm nodule on Right: benign
 Rx’s offered:
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RAI ablation versus thyroidectomy
Patient chose Thyroidectomy
RAIU
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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
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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
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Beta-blockers (hyperadrenergic symptoms)
 Hyperthyroidism:
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Anti-thyroid Drugs
– Propylthiouracil (PTU), Methimazole
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Thyroiditis:
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Radioiodine Ablation
Surgical Thyroidectomy
ASA, NSAIDS, +/- corticosteroids
Iodine (high doses Wolff Chaikoff effect)
Thyroid Structure
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Physical Exam
 Thyroid Ultrasound
 Thyroid Scan
Thyroid nodules
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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?
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Thyroid Incidentaloma (Carotid duplex, etc.)
Thyroid U/S
Benign
Characteristics
Regular border
Halo (sonolucent rim)
Hyperechoic
Egg shell calcification
N/A
Malignant
Characteristics
Irregular border
No Halo
Hypoechoic
(more vascular)
Microcalcification
Intranodular vascular spots
(color doppler)
Thyroid Scan
Thyroid nodule: risk of malignancy 6.5%
only 5-10% of nodules
Cold nodule
16-20% malignant
“Warm” Nodule
(indeterminant)
5% malignant
Hot Nodule
Tc-99m < 5% malignant
I123 < 1% malignant
Fine Needle Aspiration (FNA)
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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
or High
Scan
Hot
FNA
Not
Hot
Malignant
Rx Plummer’s
•Surgery
•RAI
Total
Thyroidectomy
Benign
Clin suspicion
Low
Insufficient Repeat FNA
Sample
+/- U/S guide
Suspicious
(Follicular)
+
Clin suspicion
High
Hemithyroidectomy
with quick section
RAI
Close
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
Yes
Follow
U/S q1y ?
Thyroid Nodule
Palpable
>15mm
TSH
Low
Normal
or High
Scan
Hot
Follow
U/S q1y
FNA
Not
Hot
Malignant
Rx Plummer’s
•Surgery
•RAI
Total
Thyroidectomy
Benign
Clin suspicion
Low
Insufficient Repeat FNA
Sample
+/- U/S guide
Suspicious
(Follicular)
+
Clin suspicion
High
Hemithyroidectomy
with quick section
RAI
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