Carbamazepine (CBZ) interfering with 24-hour urine-free cortisol

Chronic glucocorticoid excess leads to the constellation of symptoms and physical features known as Cushing's syndrome. The most useful screening test for this disease is the measurement of 24-hour urine free cortisol. Depression, chronic alcohol abuse, and psychological or physical stress all can increase urine free cortisol excretion and result in a false positive study. Drugs such as phenytoin, phenobarbitone, and primidone can interfere with the dexamethasone suppression test, but urine-free cortisol usually is normal. Carbamazepine (CBZ) is reported to increase 24 hour urine free cortisol. To our knowledge, there is no report of CBZ interfering with a urine-free cortisol assay by high performance liquid chromatography (HPLC). We report the case of a 17-year-old woman with partial complex seizure disorder treated with CBZ, 150 mg TID, who was evaluated for Cushing's syndrome because of obesity, hypertension, and hirsutism. She had no other signs of Cushing's syndrome. An overnight dexamethasone suppression test (1 mg) was abnormal (serum cortisol 11 mcg/dL at 8:00 a.m.) The 24-hour urine free cortisol, by HPLC, was elevated on two occasions: 194 mcg/24h, and 14,744 mcg/24h (<50 mcg/24h). Repeat measurements of the second sample by radioimmunoassay showed a 24-hour urine free cortisol of 128 mcg/24h. The interfering substance with HPLC assay has not been identified. It seems likely that it is a CBZ metabolite. Midnight serum cortisol level was normal at 9.9 mcg/dl, and serum corticosterone (p) showed adequate suppression (<20 ng/dL) after an overnight hydrocortisone suppression test. This is the first case report of CBZ interfering with a urine-free cortisol assay by HPLC method. Careful interpretation of 24-hour urine-free cortisol measurement is required in patients taking CBZ.