Life-threatening theophylline intoxication in a hypothyroid patient

In a hypothyroid patient who suffered also from chronic obstructive lung disease and mild congestive heart failure, treatment with 1 g/day theophylline administered orally, was followed by a life-threatening theophylline intoxication manifested by repeated epileptic fits and ventricular fibrillation, successfully reverted to sinus rhythm. The plasma theophylline was 34.7 micrograms/ml when the life-threatening arrhythmia occurred. Pharmacokinetic studies conducted during the hypothyroid state revealed a markedly prolonged theophylline plasma half-life of 29.5 h. 2 months later, after reestablishment of an euthyroid state, theophylline plasma half-life was shortened to normal, i.e. 5.7 h and the theophylline plasma level was 13.5 micrograms/ml, while the daily intake was 1 g. We conclude that hypothyroidism may predispose to theophylline intoxication, probably because of the decreased activity of the hepatic microsomal drug-metabolizing enzymes, responsible for the degradation of theophylline.