Troglitazone induces CYP3A4 activity leading to falsely abnormal dexamethasone suppression test.
After evaluating a patient who appeared to have a falsely abnormal response to the dexamethasone suppression test while taking troglitazone, we examined the effects of troglitazone on the activity of hepatic CYP3A4 and the screening tests for Cushing's syndrome. We studied five healthy women and three healthy men, aged 25 +/- 2 yr, before and after treatment with troglitazone (600 mg daily) for 28 d. Baseline 0800 h cortisol and corticosterone were similar before and after troglitazone treatment. Before troglitazone treatment, all subjects suppressed 0800 h cortisol below 1.8 micro g/dl (mean, 0.66 +/- 0.08 micro g/dl) during the 1-mg overnight dexamethasone suppression test (DST), whereas during troglitazone treatment none of the subjects suppressed 0800 h cortisol below 1.8 micro g/dl (mean, 9.0 +/- 1.8 micro g/dl). Serum dexamethasone levels decreased by 66 +/- 4%, and the erythromycin breath test measurements increased by 27 +/- 8%, indicating increased CYP3A4 activity during troglitazone treatment. The hydrocortisone suppression test (HST) was performed by administering 50 mg hydrocortisone at 2300 h. Using the criterion of suppression of 0800 h plasma corticosterone by more than 50%, the specificity of the HST was 100% both before and after troglitazone treatment. In conclusion, troglitazone induced the activity of CYP3A4 leading to falsely abnormal DST. HST is a useful alternative to the DST in patients taking medications that increase the activity of CYP3A4.
Dimaraki
Eleni V
EV
Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor, Michigan 48109, USA.
Jaffe
Craig A
CA
D000328:Adult; D000893:Anti-Inflammatory Agents; D001944:Breath Tests; D002839:Chromans / Q000009:adverse effects*; D003345:Corticosterone / Q000097:blood; D003480:Cushing Syndrome / Q000175:diagnosis*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone; D003951:Diagnostic Errors; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004917:Erythromycin / Q000493:pharmacokinetics; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000493:pharmacokinetics; D013844:Thiazoles / Q000009:adverse effects*; D045162:Thiazolidinediones; D000077288:Troglitazone
D000893:Anti-Inflammatory Agents; D002839:Chromans; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D011500:Protein Synthesis Inhibitors; D013844:Thiazoles; D045162:Thiazolidinediones; D004917:Erythromycin; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077288:Troglitazone; D003345:Corticosterone; D006854:Hydrocortisone