Insufficient adrenarche in patients with combined pituitary hormone deficiency caused by a PROP-1 gene defect

Adrenarche was evaluated in five patients, aged 17.4 +/-3 years, with combi ned pituitary hormone deficiency (CPHD), caused by a PROP-1 gene defect. Ad renocorticotrophic hormone (ACTH), cortisol and dehydroepiandrosterone sulf ate (DHEAS) were determined prior to and following the administration of co rticotropin-releasing hormone (CRH) in four of the five patients, while onl y basal values of ACTH, cortisol and DHEAS were determined in the fifth. In the four patients in whom a CRH test was carried out, the mean basal value s of cortisol, ACTH and DHEAS were 289 +/- 140 nmol/l, 4.5 +/-1.7 pmol/l an d 0.26 +/-0.36 mu mol/l, respectively. The corresponding post-CRH peak valu es were 584 +/- 204 nmol/l, 12.7 +/-3.9 pmol/l and 0.43 +/-0.41 mu mol/l. I n the fifth patient, basal ACTH, cortisol and DHEAS values were 4 pmol/l, 4 11 nmol/l, and 2.33 mu mol/l, respectively. Thus the basal and post CRH val ues of DHEAS (a marker of adrenarche) were low for age, while basal and pos t-CRH cortisol and ACTH values were within normal limits. For the interpret ation of these findings two hypotheses can be proposed: 1) The PROP-1 gene is only expressed in the pituitary, and the role of PROP-1 is related to th e maturation of the cells which synthesize the presumed adrenal androgen st imulating hormone (AASH). 2) The PROP-1 gene is also expressed in the adren al cortex and, when defective, the zona reticularis does not function appro priately. Regardless of the interpretation involved, patients with CPHD cau sed by a PROP-1 gene defect also have insufficient adrenarche. This finding has possible important pathophysiological implications.