Subclinical Thyroid Disease Karen Earlam PGY - 1

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.

Case 50 year old woman TSH = 7 mIU/L (0.27-4.20) 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???

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

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

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

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

Subclinical hypothyroidism

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

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

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

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)

Subclinical hyperthyroidism

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

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

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

Case 50 year old woman TSH = 7 mIU/L (0.27-4.20) 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???

Thank you!