A rare variant of DAX1 mutation presenting with primary adrenal insufficiency and hypogonadotropic hypogonadism

ABSTRACT DAX1 mutation causes X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in boys. Onset of adrenal insufficiency (AI) usually precedes the diagnosis of HH. Likewise, our patient was first diagnosed with primary AI at the age of 8 years and later presented at 21 years of age with poorly developed secondary sexual characteristics. The hormonal evaluation was suggestive of low luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, suggestive of hypogonadotropic hypogonadism (HH). The possibility of DAX1 mutation was considered. Subsequently, whole-exome sequencing revealed a rare variant, NR0B1; c.881T>C (p.Leu294Pro), confirming our diagnosis. Therefore, a high index of suspicion is required in patients with a past history of AI who present with pubertal delay, in whom early initiation of gonadotropins results in favorable outcomes in terms of fertility. Monitoring pubertal development is important during follow-up because early recognition can help in proper management.