1. Subclinical Thyroid Disease
Karen Earlam
PGY - 1

2. Main Objectives
1. To outline the criteria for subclinical thyroid disease.
2. To review the evidence for the clinical significance of subclinical thyroid disease.
3. To review the management of subclinical thyroid disease.

3. Case
50 year old woman
TSH = 7 mIU/L ( ) on routine screening, normal free T4/T3
Only symptoms = mild fatigue x 10 years, difficulty losing weight
Normal physical exam
Also serum cholesterol 5.70 mmol/L, LDL 3.62 mmol/L
Anti-TPO positive
Start thyroxine???

4. Definition of Subclinical Thyroid Disease
Subclinical Hypothyroidism
TSH elevated (0.27 – 4.20 mIU/L)
Free T4/T3 normal
Rule out other causes of an elevated serum TSH
Levothyroxine dosage changes (in process of achieving a steady state)
Recovering from severe nonthyroidal illness
Recovery from: postviral subacute thyroiditis, postpartum thyroiditis
Subclinical Hyperthyroidism
TSH low (0.27 – 4.20 mIU/L)
Free T4/T3 normal
Rule out other causes of low serum TSH
Overadministration of thyroid hormone
Normal pregnancy, nonthyroidal illnesses
Administration of dopamine, glucocorticoids, etc
Normal Thyroid
Subclinical Thyroid
Hypo/Hyper thyroid

5. Epidemiology
Subclinical hypothyroidism: 4 – 8.5% of population without known thyroid disease
Prevalence increases with age (esp. women > 60y, up to 20%), also in men
Elevated TSH levels: 75% values > 10mIU/L
Factors that raise likelihood: family history of thyroid disease, postpartum thyroiditis, previous head and neck cancer treated with radiation, DMT1, previous hyperthyroidism
In patients with subclinical hypothyroidism, 2 – 5% per year will progress to overt hypothyroidism
Rate of progression is higher if + antithyroid antibodies
Serum TSH returns to normal in about 5% of people after 1 year

6. Epidemiology Subclinical hyperthyroidism: much less common
If exclude patients with known thyroid disease and lower limit of TSH is 0.4mIU/L, prevalence is 2%
More common if: female, elderly, low iodine intake
More likely if: history thyroid disease, family history thyroid disease, atrial fibrillation, use amiodarone, presence of goiter
If TSH 0.1 – 0.45mIU/L = few progress to overt hyperthyroidism vs. 1 – 2% per year if TSH < 0.1 mIU/L

7. Clinical significance of disease: Why does it matter???
JAMA 2004: Subclinical Thyroid Disease, Scientific review and guidelines for diagnosis and management
Representatives from American Thyroid Association, the American Asso. of Clinical Endo, and the Endocrine Society
Reviewed literature and summarized the evidence
Relevant articles found by searching Medline, Embase, Biosis, etc.
Examined quality of evidence for strength of association with adverse consequences
Panel rated strength of available evidence as either “good”, “fair” or “insufficient” as it related to the association of treatment and outcomes

8. Subclinical hypothyroidism

9. Subclinical hypothyroidism
Cardiac implications
Cardiac disease: decreases in myocardial contractility (echo)
Unclear if affects angina, MI, atherosclerosis and cardiovascular death
No randomized studies have assessed impact of levothyroxine replacement on important clinical cardiac end points
Many small trials demonstrate improved cardiac function – not clear if clinically important
Lipids
Several studies suggest thyroid hormone therapy will reduce total and LDL cholesterol levels
However, this finding has not been confirmed in RCT’s
Systemic symptoms
Increased prevalence of hypothyroid symptoms seen in some studies, not all

10. Evaluation of Subclinical hypothyroidism
If TSH is high  repeat along with free T4 in the next 2 weeks – 3 months
Evaluate for signs and symptoms of hypothyroidism, previous tx for hyperthyroidism, thyroid gland enlargement, family hx thyroid disease
Review lipid profile
Special consideration if pregnant woman/plans for pregnancy
Insufficient evidence to recommend for/against measurement of anti-TPO antibodies

11. Management Serum TSH 4.5 – 10mIU/L Serum TSH > 10mIU/L
Repeat TFT’s q 6-12 months
Treat if symptoms compatible with hypothyroidism (no studies looking at his)
Continue therapy of there is clear symptomatic benefit
Serum TSH > 10mIU/L
Levothyroxine therapy is reasonable
Rate of progression to hypothyroidism is 5%, may prevent manifestations and consequences of hypothyroidism in those that do progress
Aim for TSH level in lower half of normal range

12. Subclinical hypothyroidism during pregnancy
Evidence rating = “fair” for adverse outcomes for either mother or fetus
Check TSH if family/personal hx of thyroid disease, signs/symptoms of hypothyroidism or goiter, DMT1, personal hx of autoimmune disorders
If TSH elevated = treat, possible association with neuropsychological complications in fetus
Monitor TSH levels q 6-8 weeks and modify dose of levothyroxine accordingly (requirements will increase)

13. Subclinical hyperthyroidism

14. Subclinical hyperthyroidism
Cardiac disease
Solid evidence for a 3x increased risk of a fib over 10 y in women and men > 60y with TSH < 0.1 mIU/L
Limited evidence for a fib if TSH 0.1 – 0.4 mIU/L
Also reported increase in LV mass, cardiac contractility, diastolic dysfunction and atrial arrythmias
Systemic symptoms
More hyperthyroid-type signs and symptoms?
Bone health
2 meta-analyses reported declines in bone mineral density during prolonged subclinical hyperthyroidism, especially if postmenopausal women (not if premenopausal)
Prolonged subclinical hyperthyroidism prior to overt hyperthyroidism may increase risk of fractures
Normalization of bone turnover may take 1 year once treatment started

15. Evaluation/Management of Subclinical hyperthyroidism
If TSH 0.1 – 0.45 mIU/L  repeat, as well as free T4/T3 (time frame based on clinical circumstances, recommend within 3 months)
Repeat within 2 weeks if patient has a fib, cardiac disease, other serious medical condition
If repeat TSH 0.1 – 0.45 mIU/L, normal free T4/T3 and no s/s cardiac disease, a fib, arrhythmias  repeat TFT’s q 3 – 12 months
May consider tx of elderly due to possible association with increased cardiovascular mortality

16. Evaluation/Management
If TSH < 0.1 mIU/L  repeat along with free T4/T3 within 4 weeks
Sooner if s/s cardiac disease, a fib, arrhythmias, important medical issues
Also recommend further evaluation, ie. thyroid uptake scan to distinguish between thyroiditis, Graves disease, nodular goiter, etc (treat if Graves or nodular thyroid disease)
Consider tx if age > 60y, osteopenia/osteoporosis, people at increased risk for heart disease, symptomatic
If younger individual = offer therapy or follow-up depending in individual considerations

17. Case
50 year old woman
TSH = 7 mIU/L ( ) on routine screening, normal free T4/T3
Only symptom = mild fatigue x 10 years, difficulty losing weight
Normal physical exam
Also serum cholesterol 5.70 mmol/L, LDL 3.62 mmol/L
Anti-TPO positive
Start thyroxine???

18. Thank you!