ACTH 1-17 and pituitary-adrenal function in human

In this study we have compared the effects of the ACTH 1-17 analogue, alsactide (Synchrodyn 1-17,) and of the ACTH 1-24 fragment, on the dynamics of ACTH-cortisol secretion. In 2 healthy women, 100 micrograms alsactide injected i.m. at 07(00) caused a much greater and sustained cortisol secretion than 100 micrograms ACTH 1-24. However, adrenocortical stimulation effected by alsactide terminated within 24 h, since plasma cortisol levels recorded 24 h after alsactide injection were even lower than the corresponding values of the previous day. In 8 other women, daily administration of 100 micrograms alsactide at 07(00) for 15-days resulted in a significant blunting (p less than 0.05) of the ACTH secretion in response to insulin-induced hypoglycemia. This finding is even more meaningful in view of the more marked blood glucose fall (p less than 0.01) observed in the post treatment insulin tolerance test. Both baseline and insulin-stimulated cortisol levels were reduced after alsactide (p less than 0.02) so that cortisol increments above baseline were of comparable magnitude before and after treatment with the ACTH analogue. In 8 additional women, no significant changes in the cortisol response to hypoglycemia, in spite of more profound blood glucose fall (p less than 0.05), were noted after a 15-day treatment with 250 micrograms ACTH 1-24 daily. In all, these findings show that ACTH 1-17, compared to ACTH 1-24, effects a much more potent stimulation of cortisol secretion which, however, terminates within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)