Pleomorphism of the HPG axis with NR0B1 gene mutation - a case report of longitudinal follow-up of a proband with central precocious puberty

Abstract

Objectives: X-linked adrenal hypoplasia congenita (AHC) is characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Herein, we report a rare case of X-linked AHC with central precocious puberty (CPP).

Case presentation: An 11-month-old male patient was found to have premature pubarche, enlargement of the penis, and frequent erection. LH and FSH levels after the GnRHa test were in the pubertal range. Direct sequencing revealed a heterozygous variant of the NR0B1 gene. The proband was treated with hydrocortisone and 9-alpha fludrocortisone because of the significantly elevated ACTH and renin activity. The secondary sexual characteristics relieved gradually. The serum testosterone and LH subsequently returned to the prepubertal range. The basal serum FSH values have been between 1.0 and 2.0 IU/L since the age of 2.25 years, with extremely low AMH levels beginning at 3 years.

Conclusions: The clinical course of CPP with NR0B1 variant may be temporary. HPG axis status of X-linked AHC may probably be pleomorphic during the longitudinal follow-up.

Keywords: NR0B1 gene variant; adrenal hypoplasia congenita; central precocious puberty.