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subclinical hypothyroidism

Etiology: 1) auto-immune 2) pharmaceutical agents a) lithium b) amiodarone or pharmaceuticals containing iodide Epidemiology: - 11% of elderly, 3% of younger population [9] Clinical manifestations: - as the name would imply, patients with subclinical hypothyroidism are asymptomatic [40] Laboratory: 1) normal levels of serum T3 & serum T4 - serum free T4 may be low-normal - measurement of serum T3 is not necessary [1] 2) increased levels of serum TSH* - values of 5-15 mIU/L are characteristic 3) repeat thyroid function tests 6-12 weeks after initial testing - values normalize in up to 30% of patients [1] 4) anti-thyroid antibodies may herald a failing thyroid a) thyroid peroxidase antibody in serum b) thyroglobulin antibody in serum - no indication to check serum thyroglobulin [43] 5) lipid panel (elevated serum LDL cholesterol) * normal range for serum TSH increases with age - < 8.0 uU/mL upper end of normal range for elderly >= 80 years [1,42] Complications: 1) possible increased risk of atherosclerosis & myocardial infarction [2] 2) increased risk of coronary artery disease & mortality [15] - cardiovascular disease mediates associations of subclinical hypothyroidism with all-cause mortality in the US general population [35] 3) adverse cardiovascular risks confined to patients < 65 years of age [19] - in the elderly, subclinical hypothyroidism may be a good prognostic indicator [18] 4) increased risk of mortality in the elderly (RR = 1.77)* [29] 5) increased risk of adverse outcomes of pregnancy a) placental abruption (RR = 3.0) b) preterm delivery (RR = 1.8) c) respiratory distress d) admission to NICU 6) increased risk of hip fracture in men (HR=2.3), but not women [13] 7) no increase in risk of cognitive impairment [15,41] * threshold serum TSH > 6.35 mIU/L [29] Management: 1) patients are presumably mildly symptomatic & could benefit from treatment with thyroxine if a) serum TSH > 10 uIU/mL, or b) cardiovascular disease, or c) elevated serum LDL cholesterol, or d) pregnant or desire to become pregnant*, or e) family history of hypothyroidism, or f) goiter, or g) positive anti-thyroid antibodies makes it likely disorder will progress to frank hypothyroidism h) high symptom burden not a reason to treat subclinical hypothyroidism in the elderly [36] 2) benefits of treatment may include: a) more favorable lipid profile b) reduced risk of cardiovascular events in patients < 70 years of age [8,13] (39% reduction) [13] c) some benefits of levothyroxine treatment in reducing cardiovascular events [26] d) supplementation with levothyroxine has not been shown to mitigate cardiovascular risk [1] (MKSAP17) 3) no evidence to support treatment [1,4] a) USPSTF recommends against routine treatment [4] b) no benefit of levothyroxine for older adults with subclinical hypothyroidism unless serum TSH > 10 mIU/L [24,30,31,38] c) no evidence for treating elderly subjects with T4 to improve cognition [11,25] d) no benefit for treating elderly >+ 80 years of age [34] e) no benefit for prevention or treatment of mood disorders including depression or thyroid-related quality of life [27,37] f) benefit for treatment of dyslipidemia, diabetes is conflicting [26] g) older patients should not be treated with T4 solely for elevated serum TSH [1,16] h) higher serum TSH & lower serum free T4 in elderly Askenazni Jews is associated with extreme longevity [18] - authors suggest treatment of subclinical hypothyroidism in the elderly may be harmful i) do not treat subclinical hypothyroidism unless serum TSH > 10 mIU/L [33,38] j) <10% of new levothyroxine prescriptions are for overt hypothyroidism - mean TSH level at which levothyroxine is initiated is ~5.5 mIU/L [39] 4) prognosis: a) may progress to overt hypothyroidism [4] - 6%* with serum TSH of 5.0-9.0 mIU/L (52% normalize TSH) [5] - 86%* with serum TSH of 15.0-19.9 mIU/L [5] - serum TSH normalized in 61% of elderly with one instance of subclinical hypothyroidism & 40% of elderly with 2 instances separated by 1 year [44] - normalization of serum TSH more likely in women negative for thyroid peroxidase antibody in serum [44] * progression to overt hypothyroidism within 3.5 years b) no evidence that early treatment is of benefit [4] c) TSH generally normalizes within 5 years if TSH < 10 mIU/L [7] d) in the elderly, resolution 46% with serum TSH of < 7 mIU/L, 10% with serum TSH > 7 mIUL [14] * treatment of pregnant women with subclinical hypothyroidism associated with: - reduced risk for pregnancy loss (11% vs 14%) - increased risk for preterm delivery (7% vs 5%) - increased risk for preeclampsia (5.5% vs 4%) - increased risk for gestational diabetes (12% vs 9%) [22] - no improvement in cognition of offspring [23] Notes: - frequently overtreated [17]

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subclinical hyperthyroidism

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hypothyroidism subclinical thyroid disease

References

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