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

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 (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyrotropin (TSH), and cyclic AMP (cAMP) were done. In all four cases, serum T4 increased significantly (134% +/- 4% vs basal level) with significant correlation to plasma cAMP level (r = 0.67, p less than 0.05). Changes in T3 and rT3 showed a marked individuality; an increase in T3 occurred in a subject with severe side effects, while the increase in rT3 was observed in a subject with mild side effects. Of the 15 children on theophylline treatment, a higher T4 level was found in 12 and a lower T3 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 T4 level. In most cases, T4 is metabolized to rT3, an inactive metabolite of T4, but in a few cases it is metabolized to T3, which might double the side effects of theophylline.