Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects

Abstract

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 μg SMS or placebo at 0830 h and 100 μg synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 μg or 63 μg) at 0900 h after 100 μg SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS. These results suggest that a single sc administration of SMS suppresses CRH-induced ACTH and cortisol secretion, but not ACTH-induced cortisol and aldosterone, and also favor the possibility that somatostatin is involved in the regulation of ACTH secretion in man. Based on the present observations, it may be worthwhile to pay attention to adrenocortical function in patients under long-term therapy with SMS. However, further study is required to establish the exact effects of SMS on adrenocortical secretion with a smaller amount of ACTH than used in this study.