Endocrine Abstracts

JOINT3746

Background: Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency (21 OHD) is the primary cause of adrenal insufficiency in Indonesia, as limited resources of hormonal and genetic laboratories can pose challenges in diagnosing rare adrenal conditions leading to missed diagnosis with high mortality. Here, we present two exceptionally rare cases of congenital adrenal insufficiency other than 21OHD.

Case presentation: Case 1: A-seven-years-old boy was admitted to the hospital due to recurrent seizures, vomiting, dehydration, and repeated severe hyponatremia without hyperkalemia. There was no consanguinity. The older sibling had a similar history and died due to seizures at the age of 4.5 yo. Physical examination showed normal neurology examination, hyperpigmentation, and dark spots on the tongue, normal penis and testicles. Laboratory examination revealed a low 17-Hydroxyprogesterone (17-OHP) level (the hallmark of 21OHD), low cortisol level, and hyponatremia. This patient was treated as an adrenal insufficiency patient with hydrocortisone and fludrocortisone, and the response to treatment was good. Exome sequencing showed a hemizygous pathogenic variant in NR0B1 ChrX(GRCh37):g.30327091dup NM_000475.5:c.391dup p.(Arg131fs) which is not reported in previous studies. Pathogenic variants of the NR0B1 gene had been described previously as causative for X-linked recessive congenital adrenal hypoplasia. Case 2: A-18-days-old female baby was admitted to the hospital because of recurrent hypoglycemia and hyperpigmentation, recurrent vomiting, and hyperpigmentation. There was no consanguinity; the older sister died at the age of 3 months with a similar condition. Physical examination showed skin hyperpigmentation, no clitoromegaly, no palpable testis, presence vagina and labia minora. Laboratory results showed low 17-OHP level, hyponatremia, hyperkalemia, hypoglycemia, and a 46,XY karyotype. This patient was treated as an adrenal insufficiency patient with hydrocortisone and fludrocortisone. Exome sequencing showed a homozygous variant in the Steroidogenic Acute Regulatory Protein (StAR) gene as the causative for autosomal recessive lipoid adrenal hyperplasia, and this is the first reported case in Indonesia.

Conclusions: Adrenal insufficiency often presents with aspecific features leading to delayed or missed diagnosis. Low 17-OHP levels should prompt clinicians to consider alternative etiologies beyond 21-OHD,

Keywords: Adrenal insufficiency, developing country, Indonesia, Steroidogenic Acute Regulatory Protein (StAR), Congenital adrenal hypoplasia