The role of somatostatin analogs in Cushing's disease

Somatostatin (SRIF) has been proposed to be of therapeutic interest in the medical treatment of Cushing's disease. While in vitro data demonstrate the presence of SRIF-receptor subtype (sst) expression in corticotroph adenomas, the current clinically available SRIF-analog Octreotide, predominantly targeting sst(2), is ineffective in lowering ACTH levels in Cushing's disease and only appears to inhibit the release of ACTH in Nelson's syndrome. In the present review, current knowledge on the physiological role of SRIF in the regulation of ACTH secretion by the anterior pituitary gland, as well as by corticotroph tumor cells is summarized. In addition, the role of glucocorticoids in regulating sst-mediated inhibition of ACTH release by corticotroph adenoma cells is discussed. Recently, it was reported that the novel multiligand SRIF-analog SOM230 might have the potential to be of therapeutic interest for Cushing's disease. On the basis of the potent suppressive effects on ACTH release by SRIF-analogs with high binding affinity to sst(5) and the observation that sst(5) expression and action is relatively resistant to glucocorticoid treatment, including the recent observation that sst(5) is the predominant sst expressed in human corticotroph adenomas, it is hypothesized that sst(5) may be a new therapeutic target for the control of ACTH and cortisol hypersecretion in patients with pituitary dependent Cushing's disease.