Endocrine Abstracts

Background and Purpose: AHC (X-linked adrenal hypoplasia congenita) is a rare cause of adrenal insufficiency due to mutations in NROB1 gene. It traditionally causes hypogonadotropic hypogonadism. Rare cases of central precocious puberty due to NROB1 mutation has been reported so far. We present two interesting cases of NROB1 mutation from a same family with different presentations. This is first case report of NROB1 mutation from Pakistan.

Case Report: Index case boy presented at 15 day of life with adrenal crises and was treated with hydrocortisone and florinef which was subsequently continued. Later, at 11 month of age he developed precocious puberty with tanner staging III, bilateral testicular volume was 6 ml, penile length of 5 cm and dark pigmented genitalia. Investigations revealed low Na and high K, high ACTH, high Renin, increase LH, FSH, & Testosterone. His short Synacthen test with 17 OHP was normal while he showed advanced bone age. Genetic mutation revealed NROB1 mutation hemizygous (variant c.327C>A(p.Cys109). He was then treated with a GnRH agonist along with steroid replacement therapy. On follow up after 6 months of treatment his testicular volume remained unchanged where as pubic hair slightly reduced. Interestingly his elder brother who is now 15 ½ years old also presented at the age of 1 month with adrenal crises and treated as primary adrenal insufficiency, is showing arrested puberty with Tanner scoring III and bilateral testicular volume 6/6 for past 1 year. His genetic mutation also revealed same NROB1 hemizygous mutation.

Conclusion: Hypogonadotropic hypogonadism is classic feature of X-linked AHC but it can also manifest as normal puberty or in rare cases as precocious puberty so spectrum of NROB1 gene is very wide. Mechanism of precocious puberty is yet to be understood. Proposed theory suggest that possibly loss of one or more transcription factor which suppress puberty encoding gene.

Keywords: Hypogonadotropic hypogonadism, precocious puberty, adrenal insufficiency