Subclinical hypothyroidism (SH), defined by elevated serum levels of thyroid 
stimulating hormone (TSH) with normal levels of free thyroid hormones, is common 
in adults, especially in women over 60 years of age. Among individuals with this 
condition, up to two-thirds have serum TSH levels between 5-10 mU/L and thyroid 
autoantibodies; almost half of them may progress to overt thyroid failure, the 
annual percent risk increasing with serum TSH level. There is evidence that 
elevated TSH levels in patients with SH do not reflect pituitary compensation to 
maintain euthyroidism, but a mild tissue hypothyroidism sensu strictu. When 
lasting more than 6-12 months, SH may be associated with an atherogenic lipid 
profile, a hypercoagulable state, a subtle cardiac defect with mainly diastolic 
dysfunction, impaired vascular function, and reduced submaximal exercise 
capacity. The deviation from normality usually increases with serum TSH level 
('dosage effect' phenomenon). Restoration of euthyroidism by levothyroxine (LT4) 
treatment may correct the lipid profile and cardiac abnormalities, especially in 
patients with an initially higher deviation from normality and higher serum TSH 
levels. Importantly, a strong association between SH and atherosclerotic 
cardiovascular disease, independent of the traditional risk factors, has been 
recently reported in a large cross-sectional survey (the Rotterdam Study). 
However, whether SH confers a high risk for cardiovascular disease, and whether 
LT4 therapy has a long-term benefit that clearly outweighs the risks of 
overzealous treatment in these individuals, remain topics of controversy. 
Therefore, until randomized, controlled, prospective, and adequately powered 
trials provide unequivocal answers to these critical questions, it is advisable 
to prescribe LT4 therapy on a case-by-case basis, taking into account the risk 
of progressive thyroid failure and the risk of cardiovascular events.