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 sourc e of ACTH in patients with Gushing's syndrome. Psychiatric symptoms ar e common in patients with Gushing's syndrome, and many patients with p sychiatric illnesses may show disturbances of function of the pituitar y-adrenal axis; both of these groups of patients may be receiving benz odiazepine drugs when presenting for evaluation of their possible endo crine problems. Both animal and human studies suggest that interaction s occur between benzodiazepines and the hypotharamo-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 Gushing's syndrome. RESULTS Temazepam significantly inhibited the peak serum/plasma levels and are a under the curve for circulating cortisol and ACTH in normal subjects after GRH, but there was no such difference after temazepam in patien ts with Gushing's syndrome. CONCLUSIONS Our results have shown that te mazepam inhibits the pituitary-adrenal responses to human GRH in norma l subjects, but not in those with Gushing's syndrome. We believe that inhibition of endogenous AVP by temazepam is the most likely explanati on for our findings in healthy volunteers: the hypercortisolaemia In G ushing's syndrome suppresses the release of both endogenous CRH and AV P in portal blood which then results in abolition of the temazepam ind uced 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 undergoi ng endocrine assessment.