Insufficient Adrenarche in Patients with Combined Pituitary Hormone Deficiency Caused by a PROP A Gene Defect

Adrenarche was evaluated in five patients, aged 17.4 ± 3 years, with combined pituitary hormone deficiency (CPHD), caused by a PROP-1 gene defect. Adrenocorticotrophic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were determined prior to and following the administration of corticotropinreleasing hormone (CRH) in four of the five patients, while only 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 values of cortisol, ACTH and DHEAS were 289 ±140 nmol/1, 4.5 ±1.7 μmol/1 and 0.26 ± 0.36 μmol/1, respectively. The corresponding post-CRH peak values were 584 ± 204 μmol/1, 12.7 ± 3.9 μmol/1 and 0.43 ± 0.41 μmol/1. In the fifth patient, basal ACTH, cortisol and DHEAS values? were 4 μmol/1, 411 μmol/1, and 2.33 μmol/1, respectively. Thus the basal and post CRH values of DHEAS (a marker of adrenarche) were low for age, while basal and post-CRH cortisol and ACTH values were within normal limits. For the interpretation 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 the maturation of the cells which synthesize the presumed adrenal androgen stimulating hormone (AASH). 2) The PROP-1 gene is also expressed in the adrenal cortex and, when defective, the zona reticularis does not function appropriately. Regardless of the interpretation involved, patients with CPHD caused by a PROP-1 gene defect also have insufficient adrenarche. This finding has possible important pathophysiological implications.