Effect of sustained-release theophylline administration on pituitary-thyroid axis

Abstract The effect of therapeutic doses of theophylline on the pituitary-thyroid axis was studied in four normal adults and in 15 asthmatic children on theophylline treatment. In the four normal adults, sustained-release theophylline was administered every 12 hr for 60 hr, and serial determinations of serum theophylline, thyroxine (T 4 ), triiodothyronine (T 3 ), reverse triiodothyronine (rT 3 ), thyrotropin (TSH), and cyclic AMP (cAMP) were done. In all four cases, serum T 4 increased significantly (134% ± 4% vs basal level) with significant correlation to plasma cAMP level (r = 0.67, p 3 and rT 3 showed a marked individuality; an increase in T 3 occurred in a subject with severe side effects, while the increase in rT 3 was observed in a subject with mild side effects. Of the 15 children on theophylline treatment, a higher T 4 level was found in 12 and a lower T 3 level in nine at 1 wk, but these values returned to the previous level after 4 wk. These results indicate that the therapeutic doses of theophylline significantly but transiently increased the serum T 4 level. In most cases, T 4 is metabolized to rT 3 , an inactive metabolite of T 4 , but in a few cases it is metabolized to T 3 , which might double the side effects of theophylline.