Relationships between ghrelin, hypothalamic-pituitary-adrenal- and GH/IGF1 axes in patients treated for congenital adrenal hyperplasia

Ghrelin and the GH secretagogue receptors (GHS-R) are expressed in several peripheral tissues, including adrenal glands. The hypothalamic-pituitaryadrenal axis of patients with 21-hydroxylase deficiency (21OH-D) can be only partially balanced after treatment. This could interfere with the ghrelin/GH/ IGF1 axis, contributing to the poor auxological outcome of these patients. We studied the possible short term effects of corticosteroids administration on the ghrelin/GH/IGF1 and the CRF/ACTH/adrenal axes in CAH patients, examining thirty-seven 21OH-D patients (17 M, 20 F; 13 SW, 11 SV, 13 NC forms). The patients avoided for one day the evening doses of glico- and mineralo-corticoids; the morning after, two blood samples were drawn (8:00 a. m. and 10:30-11:00 a.m.), the first immediately before and the second after an evening+morning dose of therapy. In both samples glycaemia, ghrelin, GH, IGF1, CRF, ACTH, cortisol, D4-androstenedione (D4-A), 17OH-progesterone (17OHP), insulin, plasma renin activity (PRA) were assayed. As expected, the pre/post treatment evaluation showed a statistically significant rise in cortisol and a fall in ACTH, 17OHP and D4-A levels; the same pattern of cortisol was shown by ghrelin, glycaemia and PRA, while IGF1 levels decreased; no significant differences were found for Insulin, CRF and GH levels. Analysis in a multiple regression model, showed that plasma ghrelin changes were mainly due to changes of D4-A (pre and post therapy; F=6.465, P=0.0136) and at a minor extent to changes of GH (only post therapy; F=4.447, P=0.044). Ghrelin showed to be influenced from acute corticosteroid therapy as were the other hormones involved in the hypothalamic-pituitary-adrenal and GH/IGF1 axes; interestingly, a similar ghrelin/D4-A negative correlation was found from Gambineri et al. in a group of obese women with polycystic ovary syndrome; a potential negative effect on ghrelin levels can be hypothesized for the CAH patients whose androgens could not be well controlled with treatment.