BACKGROUND: Subclinical hypothyroidism is defined as an elevated serum 
thyroid-stimulating hormone (TSH) level with normal free thyroid hormones 
values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general 
population, and up to 15% to 18% in women who are over 60 years of age. There is 
considerable controversy regarding the morbidity, the clinical significance of 
subclinical hypothyroidism and if these patients should be treated.
OBJECTIVES: To assess the effects of thyroid hormone replacement for subclinical 
hypothyroidism.
SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. 
Ongoing trials databases, reference lists and abstracts of congresses were 
scrutinized as well.
SELECTION CRITERIA: All studies had to be randomised controlled trials comparing 
thyroid hormone replacement with placebo or no treatment in adults with 
subclinical hypothyroidism. Minimum duration of follow-up was one month.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality 
and extracted data. We contacted study authors for missing or additional 
information.
MAIN RESULTS: Twelve trials of six to 14 months duration involving 350 people 
were included. Eleven trials investigated levothyroxine replacement with 
placebo, one study compared levothyroxine replacement with no treatment. We did 
not identify any trial that assessed (cardiovascular) mortality or morbidity. 
Seven studies evaluated symptoms, mood and quality of life with no statistically 
significant improvement. One study showed a statistically significant 
improvement in cognitive function. Six studies assessed serum lipids, there was 
a trend for reduction in some parameters following levothyroxine replacement. 
Some echocardiographic parameters improved after levothyroxine replacement 
therapy, like myocardial relaxation, as indicated by a significant prolongation 
of the isovolumic relaxation time as well as diastolic dysfunction. Only four 
studies reported adverse events with no statistically significant differences 
between groups.
AUTHORS' CONCLUSIONS: In current RCTs, levothyroxine replacement therapy for 
subclinical hypothyroidism did not result in improved survival or decreased 
cardiovascular morbidity. Data on health-related quality of life and symptoms 
did not demonstrate significant differences between intervention groups. Some 
evidence indicates that levothyroxine replacement improves some parameters of 
lipid profiles and left ventricular function.