A small study of seven kids with a rare adrenal gland problem (MC2R deficiency) found they all hit puberty earlier than usual. The researchers think the high stress hormone ACTH might be turning on kisspeptin neurons, which can jump‑start puberty, but they didn't find any genetic mutations in the usual puberty‑related genes.

Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations. Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2, P4, P6, and P7). All clinical data were obtained retrospectively. Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found. Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.