Korbonits M, Trainer P J, Edwards R, Besser G M, Grossman A B
Department of Endocrinology, St. Bartholomew's Hospital, London, UK.
Clin Endocrinol (Oxf). 1995 Jul;43(1):29-35. doi: 10.1111/j.1365-2265.1995.tb01889.x.
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 CRH.
We have investigated the effects of 20 mg oral temazepam or placebo on serum cortisol and plasma ACTH after the administration of 100 micrograms i.v. human CRH in 12 healthy volunteers and in 9 patients with Cushing's syndrome.
Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating cortisol and ACTH in normal subjects after CRH, but there was no such difference after temazepam in patients with Cushing's syndrome.
Our results have shown that temazepam inhibits the pituitary-adrenal responses to human CRH 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.
促肾上腺皮质激素释放激素（CRH）刺激试验已成为鉴别库欣综合征患者促肾上腺皮质激素（ACTH）来源的有力工具。精神症状在库欣综合征患者中很常见，许多患有精神疾病的患者可能存在垂体-肾上腺轴功能紊乱；这两组患者在因可能的内分泌问题接受评估时都可能正在服用苯二氮䓬类药物。动物和人体研究均表明苯二氮䓬类药物与下丘脑-垂体-肾上腺轴之间存在相互作用。因此，我们评估了一种苯二氮䓬类药物对垂体-肾上腺对CRH反应的影响。
我们研究了12名健康志愿者和9名库欣综合征患者静脉注射100微克人CRH后，口服20毫克替马西泮或安慰剂对血清皮质醇和血浆ACTH的影响。
替马西泮显著抑制了正常受试者在CRH刺激后循环皮质醇和ACTH的血清/血浆峰值水平及曲线下面积，但在库欣综合征患者中，服用替马西泮后无此差异。
我们的结果表明，替马西泮可抑制正常受试者垂体-肾上腺对人CRH的反应，但对库欣综合征患者无此作用。我们认为替马西泮对内源性血管加压素（AVP）的抑制作用最有可能解释我们在健康志愿者中的发现：库欣综合征患者的高皮质醇血症抑制了门静脉血中内源性CRH和AVP的释放，进而导致如我们的患者所见，替马西泮诱导的垂体-肾上腺对外源性CRH反应降低的作用被消除。在接受内分泌评估的患者使用这些化合物时，显然应考虑苯二氮䓬类药物的这些作用。
