A randomized double-blind crossover trial to investigate the efficacy of screening for adult hypothyroidism

Abstract

To assess the value of population screening for adult hypothyroidism. Healthy people attending for a general health assessment. A thyroid-stimulating hormone (TSH) measurement was performed on people attending for a general health assessment (women aged 50-79 [35-49 with a family history of thyroid disease] and men aged 65-79). Those with TSH levels above 4.0 mU/L were invited to join a randomized double-blind crossover trial of thyroxine and placebo, each given in random order for four months. On entry a second blood sample was collected for a TSH measurement after the end of the trial to determine whether this would help select individuals for thyroxine treatment. The daily thyroxine dose started at 50 µg and if necessary was increased to achieve a TSH level of 0.6-2.0 mU/L. There were 341 (8%) people with a TSH level above 4.0 mU/L, 110 met eligibility criteria (64 agreed to participate), and 56 (49 women, 7 men) completed the trial. Among the 15 individuals with a repeat TSH measurement above 4.5 mU/L, 11 reported feeling better on thyroxine than placebo and none reported feeling better on placebo (P = 0.001; four felt no different), indicating that in this group 73% benefitted (i.e. 11/15; 95% CI 45-92%). The main symptoms relieved were tiredness and loss of memory. There was no indication of harm. In the 41 individuals with a repeat serum TSH of 4.5 mU/L or less: 10 reported feeling better on thyroxine than placebo and 16 better on placebo (P = 0.42, 15 felt no different). Thus about 8% of men and women in the specified age groups had a TSH above 4.0 mU/L, and of these about a quarter had a repeat TSH above 4.5 mU/L, of whom about half would benefit from thyroxine treatment. The results indicate that screening for hypothyroidism would be worthwhile. Approximately 1% of people screened would have a better quality of life. Pilot screening programmes for adult hypothyroidism are justified.