Eight randomised controlled trials (RCTs) investigating hypothyroidism (n>291, one study did not state sample size) were included in the review. The duration of follow-up ranged from 6 to 12 months.
Of the 8 RCTs, five were rated as poor quality, two as fair and one as good.
Efficacy of treatment for subclinical hypothyroidism (8 studies).
One study reported a statistically significant improvement in symptoms in those with Graves' disease, measured using the Cooper Questionnaire, with levothyroxine compared with placebo (P=0.037). This was deemed the highest quality trial. Another, lower quality, study reported no significant difference in symptoms between the levothyroxine and placebo group in this subgroup of patients.
Two studies, one of people with Graves' disease and one of people with Hashimoto's thyroiditis, reported a statistically significant pre-post reduction in lipids in those treated with levothyroxine, with no reduction in the placebo group. However, when the treatment and placebo groups were compared directly, there was no statistically significant difference in lipids in either trial.
Three trials of people (primarily women) with subclinical hypothyroidism who were not previously treated for Graves' disease reported no effect of levothyroxine on symptoms or lipids, one reported small improvements in cognitive measures, and one a 0.9 mmol/L reduction in LDL cholesterol. Two of these studies were deemed to have poor internal validity.
Adverse events (3 studies).
One study reported a drop-out rate of 10% (2 people) due to nervousness and palpitations, another 11% (2 people) due to unspecified complications, while the third reported increased anxiety scores in the levothyroxine group.