Effect of SOM230 on human and rat adrenal secretion in vitro

SOM230, a recently developed somatostatin analogue, has been tested in patients with Cushing's disease with promising results. Experimental evidence indicates a pituitary site of action but no data is yet available on any direct adrenal effect on cortisol secretion. This aspect of the analogue's action appears worth investigating as some patients with Cushing's syndrome have been known to experience adrenal insufficiency soon after initiation of SOM230 treatment. Aim of the current study was to evaluate whether SOM230 modulates corticosteroid secretion by normal adrenals in vitro. Methods: Primary cultures from 6 normal human adrenals and 6 rat adrenals were incubated with 10-100 nM SOM230 with and without 10 nM ACTH. Cortisol/corticosterone levels in medium were measured after 4 and 24 hours. Results: 10 nM SOM230 significantly increased corticosteroid levels after 24h incubation in both human (131.4 ± 1.55% of baseline, p<0.05) and rat (138.1 ± 15.99%, p<0.05) adrenals; lesser effects were observed with 100 nM SOM (120.4 ± 9.33% p<0.05; 117.3 ± 15.49% N.S., for human and rat adrenals, respectively). The corticosteroid secretory response to ACTH was unaffected by SOM230 co-incubation (at 24h human adrenals: cortisol 105.6 ± 7.16% and 108.4 ± 6.99% of ACTH-stimulated wells for 10 nM and 100 nM SOM230, NS, respectively; rat adrenals: corticosterone 98.3 ± 12.11 and 91.8 ± 12.55% of ACTH-stimulated wells for 10 nM and 100 nM SOM230, respectively, NS.) Conclusions: SOM230 exerted an unexpected, moderate stimulatory effect on adrenal corticosteroid secretion in vitro. This argues against an additional, direct adrenal inhibitory effect of SOM230 in patients with Cushing's syndrome.