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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
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2.
How would you characterize her hypothyroidism? What are the ramifications of pregnancy to thyroid function/dysfunction?
FT4
High Low 1 Hypothyroid 2 thyrotoxicosis
Endo consult FT3, rT3 MRI, -SU
If equivocal
RAIU
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
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2. 3. 4. 5.
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
85% (peripheral conversion) 15%
Protein* binding
+ 0.03% free T4
T3
Protein* binding
(10-20x less than T4)
+ 0.3% free T3
* TBG
TSH Assay
(0.4-5 mU/L)
Thyrotoxicosis / 2 hypothyroidism
Unable to detect lower range of normal
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?
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)
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
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 (Hashimotos) 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 depression
When studied, no association between postpartum depression/thyroiditis Overlapping symtoms, R/O thyroid before start antidepressents
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
Case 2
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2. 3.
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When to treat Subclinical thyroid dysfunction? Naturopathic thyroid remedies Hypothryoidism Rx other than Levothyroxine What is Wilsons Thyroid Disease?
Subclincal Hypothyroidism
TSH, normal FT4 Most asymptomatic & dont 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
Men 0% per year Women 1.5% per year TMNG or toxic adenoma present 5% per year Any cardiac disease (CAD, AFIB, etc.) Age > 60 (10 year risk AFIB 32%, 10% if normal TSH) TMNG or toxic adenoma Osteoporosis
Indications to Rx:
Case 2
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2. 3.
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When to treat Subclinical thyroid dysfunction? Naturopathic thyroid remedies (Thyrosol) Hypothryoidism Rx other than Levothyroxine What is Wilsons Thyroid Disease?
Hashimotos Disease
Most common cause of hypothyroidism in North America (not idodine defeciency!) Autoimmune lymphocytic thyroiditis Females > Males, Runs in Families Antithyroid antibodies:
Hashimotos Disease
Treatment:
Thyroid Hormone Replacement Levothyroxine (T4) T3?, T4/T3 combo?, dessicated thyroid? In fact, iodine may decrease hormone production Wolff-Chaikoff effect (lack of escape)
Case 2
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2. 3.
4.
When to treat Subclinical thyroid dysfunction? Naturopathic thyroid remedies Hypothryoidism Rx other than Levothyroxine What is Wilsons Thyroid Disease?
Treatment of Hypothyroidism
Normal Daily Thyroid Secretion Rate: T4 = 100 ug/day T3 = 6 ug/day ( ratio T4:T3 = 14:1 )
T4
85% (peripheral conversion) 15%
Protein* binding
+ 0.03% free T4
T3
Protein* binding
(10-20x less than T4)
+ 0.3% free T3
T3 10 1 < 24h
Secreted by thyroid
100 ug/d
6 ug/d
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 dont feel normal on Synthroid even though my blood tests are normal. Free T4, Free T3
Narrow range of normal, but still a range! Adjust dose for a lower TSH still in the normal range?
No human studies Rodents: High T4 and normal T3 tissue levels
Liothyronine (T3)
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
In an ideal world
Mixed compound with T4:T3 = 14:1 T3 component slow release formulation Resultant:
Case 2
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2. 3.
4.
When to treat Subclinical thyroid dysfunction? Naturopathic thyroid remedies Hypothryoidism Rx other than Levothyroxine What is Wilsons Thyroid Disease?
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)
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
Case 4
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
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! (-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
Anti-thyroid Drugs
Propylthiouracil (PTU), Methimazole
Thyroiditis:
Thyroid Structure
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 U/S
Benign Characteristics Regular border Halo (sonolucent rim) Hyperechoic Malignant Characteristics Irregular border No Halo Hypoechoic (more vascular) Microcalcification
Intranodular vascular spots (color doppler)
Thyroid Scan
Thyroid nodule: risk of malignancy 6.5%
Cold nodule
16-20% malignant
Warm Nodule
(indeterminant) 5% malignant
Hot Nodule
Tc-99m < 5% malignant I123 < 1% malignant
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
TSH
Low Normal or High Benign Clin suspicion Low
FNA
Insufficient Repeat FNA Sample +/- U/S guide Clin suspicion High
Malignant
Suspicious (Follicular)
Close
Incidentaloma
(Size < 15mm) Hx of XRT exposure? FHx of thyroid cancer? Malign features on U/S? Age < 20 or > 60? Graves Disease? Familial Adenomatosis Polyposis
Thyroid Nodule
Palpable >15mm
Yes
TSH
Low Normal or High Benign Clin suspicion Low
FNA
Insufficient Repeat FNA Sample +/- U/S guide Clin suspicion High
Malignant
Suspicious (Follicular)
Close