Diagnosis of Thyroid Disorders

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Diagnosis of Thyroid Disorders

• William Harper, MD, FRCPC
• Endocrinology Metabolism
• Assistant Professor of Medicine, McMaster
  University
• www.drharper.ca

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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 lt 0.01 mU/L
• FT4 12 pM, FT3 2.1 pM

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Case 1

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

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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, a-SU

MRI, etc.
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TRH Stimulation test
A) 1 Hypothyroidism B) Central Hypothyroidism C)
Euthyroid D) 1 Thyrotoxicosis
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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

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Thyroid Tests

1. Thyroid Function
2. Iodine Kinetics
3. Thyroid Structure
4. FNA
5. Thyroid Antibodies
6. Thyroglobulin

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Normal Daily Thyroid Secretion Rate T4 100
ug/day T3 6 ug/day ( ratio T4T3 141 )
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
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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

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TSH Assay(0.4-5 mU/L)

• Early RIA lt 1.0 mU/L
• Thyrotoxicosis / 2º hypothyroidism
• Unable to detect lower range of normal
• Monoclonal SEN lt 0.1 mU/L
• Super SEN lt 0.01 mU/L

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Case 1

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

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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

• 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)

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LT4 dose adjustment in PregnancyNeed TSH at
baseline q2mos while pregnantStarting LT4 2
ug/kg/d and check TSH q4wk until euthythyroid
TSH Dose Adjustment
TSH increased but lt 10 Increase dose by 50 ug/d
TSH 10-20 Increase dose by 50-75 ug/d
TSH gt 20 Increase dose by 100 ug/d
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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

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Postpartum Thyroiditis

• 5 (3-16) postpartum women (25 T1DM)
• Up to 1 year postpartum (most 1-4 months)
• Lymphocytic infiltration (Hashimotos)
• Postpartum ? Exacerbation of all autoimmune dx
• 25-50 persistant hypothyroidism
• Small, diffuse, nontender goitre
• Transiently thyrotoxic ? Hypothyroid

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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)

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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

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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 Wilsons Disease

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Case 2

• When to treat Subclinical thyroid dysfunction?
• Naturopathic thyroid remedies
• Hypothryoidism Rx other than Levothyroxine
• What is Wilsons Thyroid Disease?

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Subclincal Hypothyroidism

• ? TSH, normal FT4
• Most asymptomatic dont need Rx (monitor TSH
  q2-5y)
• Rx Indications
• Increased risk of progression
• TSH gt 10, Female gt 50 y.o.
• Anti-TPO Ab titre gt 1100,000 ?
• Goitre present ?
• Dyslipidemia?
• Total cholesterol (TC) ? 6-8 if TSH gt 10 and TC
  gt 6.2 nM
• Symptoms?
• Pregnancy, Infertility, Ovulatory Dysfn.

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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 gt 60 (10 year risk AFIB 32, 10 if normal
  TSH)
• TMNG or toxic adenoma
• Osteoporosis

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Case 2

• When to treat Subclinical thyroid dysfunction?
• Naturopathic thyroid remedies (Thyrosol)
• Hypothryoidism Rx other than Levothyroxine
• What is Wilsons Thyroid Disease?

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Hashimotos Disease

• Most common cause of hypothyroidism in North
  America (not idodine defeciency!)
• Autoimmune
• lymphocytic thyroiditis
• Females gt Males, Runs in Families
• Antithyroid antibodies
• Thyroglobulin Ab
• Microsomal Ab
• TSH-R Ab (block)

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Hashimotos 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)

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Case 2

• When to treat Subclinical thyroid dysfunction?
• Naturopathic thyroid remedies
• Hypothryoidism Rx other than Levothyroxine
• What is Wilsons Thyroid Disease?

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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 ?

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Normal Daily Thyroid Secretion Rate T4 100
ug/day T3 6 ug/day ( ratio T4T3 141 )
T4
Protein binding 0.03 free T4
85 (peripheral conversion)
T3
Protein binding 0.3 free T3
15
(10-20x less than T4)
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T4 T3
Potency 1 10
Protein Bound 10-20 1
Half-Life 5-7d lt 24h
Secreted by thyroid 100 ug/d 6 ug/d
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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

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Levothyroxine (T4)

• Average dose 1.6 ug/kg
• Age gt 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

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I still dont 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

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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!)

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T3/T4 Liotrix

• Thyrolar
• Combo pill of T3 and T4
• Ratio of T4T3 41 (not 141)
• T3 still not slow release
• Few small studies showing benefit
• 1999 NEJM study 33 patients
• Benefit mood cognitive function
• Not available in Canada

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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 T4T3
• Variable
• Still not physiologic, often too high in T3
  (T4T3 31)

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In an ideal world

• Mixed compound with T4T3 141
• 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

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Case 2

• When to treat Subclinical thyroid dysfunction?
• Naturopathic thyroid remedies
• Hypothryoidism Rx other than Levothyroxine
• What is Wilsons Thyroid Disease?

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Wilsons Syndrome

• Wilsons disease copper toxicity ? liver failure
• Wilsons Syndrome
• Dr. E. D. Wilson discovered this condition and
  named it after himself in late 1980s
• Decreased body temperature (low normal range)
• Hypothyroid symptoms (nonspecific)
• Normal thyroid function tests
• Impaired T4 ? T3 conversion
• Build up of reverse T3
• Treat with Wilsons T3-therapy (presumably T3)

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Sick Euthyroid Syndrome, not Wilsons syndrome!
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Wilsons 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

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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 lt 0.05 mU/L, FT4 19 pM, FT3 6.9 pM
• RAIU/Scan 45 RAIU, hot nodule on Left

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Case 4

• FNA of 3cm nodule on Right benign
• Rxs offered
• RAI ablation versus thyroidectomy
• Patient chose Thyroidectomy

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RAIU

• Oral dose of I131 5 uCi (or I123 200 uCi but more
  )
• Measure neck counts _at_ 24h (/- 4h if suspect high
  turnover)
• RAIU neck counts bkgd (thigh counts) x 100
• pill counts - bkgd

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RAIU

• Normal 4h RAIU 5-15
• 24h RAIU
• gt25 Hyperthyroid
• 20-25 Equivocal (check TSH)
• 9-20 Normal
• 5-9 Equivocal (check TSH)
• lt5 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)

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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)

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Thyroid Structure

• Physical Exam
• Thyroid Ultrasound
• Thyroid Scan

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Thyroid nodules

• U/S more sensitive than P.E., particularly for
  nodules that are lt 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.)

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Thyroid U/S
Benign Characteristics Malignant Characteristics
Regular border Halo (sonolucent rim) Irregular border No Halo
Hyperechoic Hypoechoic (more vascular)
Egg shell calcification Microcalcification
N/A Intranodular vascular spots (color doppler)
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Thyroid Scan
Thyroid nodule risk of malignancy 6.5
only 5-10 of nodules
Cold nodule 16-20 malignant
Hot Nodule Tc-99m lt 5 malignant I123 lt 1
malignant
Warm Nodule (indeterminant) 5 malignant
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Fine Needle Aspiration (FNA)

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

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Thyroid Nodule Palpable gt15mm
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 Plummers
• Surgery
• RAI

Hemithyroidectomy with quick section
Total Thyroidectomy

-
RAI
Close
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Incidentaloma (Size lt 15mm) Hx of XRT
exposure? FHx of thyroid cancer? Malign features
on U/S? Age lt 20 or gt 60? Graves
Disease? Familial Adenomatosis Polyposis
Thyroid Nodule Palpable gt15mm
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 Plummers
• Surgery
• RAI

Hemithyroidectomy with quick section
Total Thyroidectomy

-
RAI
Close