BENZODIAZEPINES ATTENUATE THE PITUITARY-ADRENAL RESPONSES TO CORTICOTROPIN-RELEASING HORMONE IN HEALTHY-VOLUNTEERS, BUT NOT IN PATIENTS WITH CUSHINGS-SYNDROME

OBJECTIVE The corticotrophin-releasing hormone (CRH) stimulation test has become established as a powerful tool in differentiating the source of ACTH in patients with Cushing's syndrome. Psychiatric symptoms are common in patients with Cushing's syndrome, and many patients with psychiatric illnesses may show disturbances of function of the pituitary-adrenal axis; both of these groups of patients may be receiving benzodiazepine drugs when presenting for evaluation of their possible endocrine problems. Both animal and human studies suggest that interactions occur between benzodiazepines and the hypothalamo-pituitary-adrenal axis. We have therefore evaluated the effects of a benzodiazepine drug on the pituitary-adrenal response to GRH. DESIGN We have investigated the effects of 20 mg oral temazepam or placebo on serum cortisol and plasma AGTH after the administration of 100 mu g i.v. human CRH in 12 healthy volunteers and in 9 patients with Cushing's syndrome. RESULTS Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating cortisol and ACTH in normal subjects after GRH, but there was no such difference after temazepam in patients with Cushing's syndrome. CONCLUSIONS Our results have shown that temazepam inhibits the pituitary-adrenal responses to human GRH in normal subjects, but not in those with Cushing's syndrome. We believe that inhibition of endogenous AVP by temazepam is the most likely explanation for our findings in healthy volunteers: the hypercortisolaemia In Cushing's syndrome suppresses the release of both endogenous CRH and AVP in portal blood which then results in abolition of the temazepam induced reduction in the pituitary-adrenal response to exogenous CRH, as seen in our patients. These effects of benzodiazepines should clearly be taken into account in patients using these compounds while undergoing endocrine assessment.