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Troglitazone induces CYP3A4 activity leading to falsely abnormal dexamethasone suppression test
Eleni V Dimaraki1, Craig A Jaffe
1Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor, Michigan 48109, USA.
The Journal of Clinical Endocrinology and Metabolism
|July 5, 2003
Summary
Troglitazone falsely elevates dexamethasone suppression test (DST) results by increasing CYP3A4 activity. The hydrocortisone suppression test (HST) remains accurate, offering a reliable alternative for Cushing
Area of Science:
- Endocrinology
- Pharmacology
- Clinical Chemistry
Background:
- Troglitazone, a medication, was observed to cause a falsely abnormal dexamethasone suppression test (DST).
- This observation prompted an investigation into troglitazone's effects on hepatic CYP3A4 activity and its impact on Cushing's syndrome screening tests.
Purpose of the Study:
- To examine the effects of troglitazone on hepatic CYP3A4 activity.
- To evaluate the impact of troglitazone on the accuracy of screening tests for Cushing's syndrome, specifically the DST and hydrocortisone suppression test (HST).
Main Methods:
- Eight healthy subjects (5 women, 3 men) were studied before and after 28 days of troglitazone treatment (600 mg daily).
- The 1-mg overnight dexamethasone suppression test (DST) and the hydrocortisone suppression test (HST) were performed.
- Hepatic CYP3A4 activity was assessed using the erythromycin breath test, and serum dexamethasone levels were measured.
Main Results:
- Troglitazone treatment significantly increased hepatic CYP3A4 activity, as indicated by increased erythromycin breath test measurements and decreased serum dexamethasone levels.
- None of the subjects suppressed cortisol below 1.8 micro g/dl during the DST after troglitazone treatment, compared to all subjects suppressing cortisol before treatment.
- The HST demonstrated 100% specificity in detecting adequate hydrocortisone suppression both before and after troglitazone treatment.
Conclusions:
- Troglitazone induces hepatic CYP3A4 activity, leading to falsely abnormal results on the dexamethasone suppression test (DST).
- The hydrocortisone suppression test (HST) is a reliable alternative to the DST for patients taking medications that induce CYP3A4 activity, such as troglitazone.