Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial

Objectives To determine whether thyroxine treatment is effective in patient s with symptoms of hypothyroidism but with thyroid function tests within th e reference range, and to investigate the effect of thyroxine treatment on psychological and physical Wellbeing in healthy participants. Design Randomised double blind placebo controlled crossover trial. Setting Outpatient clinic in a general hospital. Participants 25 patients with symptoms of hypothyroidism who had thyroid fu nction tests within the reference range, and 19 controls. Methods Participants were given thyroxine 100 mug or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the o ther to take once a day for 12 weeks. All participants were assessed physio logically and psychologically at baseline and on completion of each phase. Main outcome measures Thyroid function tests, measures of cognitive functio n and of psychological and physical wellbeing. Results 22 patients and 19 healthy controls completed the study. At baselin e, patients' scores on 9 out of 15 psychological measures were impaired whe n compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy par ticipants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P < 0.01). However, pati ents' scores from psychological tests when taking thyroxine were no differe nt from those when taking placebo except for a poorer performance on one vi sual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in p atients and controls while they were taking thyroxine, confirming complianc e with treatment. Although serum concentrations of free triioclothyronine i ncreased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the contro ls. Conclusions Thyroxine was no more effective than placebo in improving cogni tive function and psychological wellbeing in patients with symptoms of hypo thyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants.