12212 A Rare Case Of Central Precocious Puberty In A Male Infant With Adrenal Hypoplasia Congenita

Abstract Disclosure: A. Mastoropoulou: None. A.H. Lane: None. Introduction: We describe a male with Adrenal Hypoplasia Congenita (AHC) caused by a novel mutation in NR0B1, who was noted at 9 months of age to have central precocious puberty (CPP). Clinical case: A 3 week-old full-term male presented with hypothermia and lethargy, and a 0.3 kg weight loss since birth. Labs were consistent with adrenal crisis: Na 109 mmol/L, K 10.4 mmol/L, Ca 12.2 mg/dL, glucose 43 mg/dL. He was stabilized with stress dose hydrocortisone (HC), insulin and antibiotics, and was admitted. Subsequent labs revealed cortisol 3.5 ug/dL (4.6-23), ACTH 1,123 pg/mL (7.2-63), 17OHP 181 ng/dL (<199), and a renin of 180 ng/mL/h (1.7-11.2) with aldosterone 14.9 ng/dL (6-179). Abdominal ultrasound was remarkable for non-visualization of the adrenal glands. The patient was discharged with HC, fludrocortisone and sodium supplementation with good tolerance and interval weight gain and normal electrolytes. Genetic testing identified a novel pathogenic c.707G>A [p.Trp236Ter] nonsense variant in the DNA-binding domain of NR0B1 (DAX-1). At 9 months of age, penile enlargement with prepubertal testes was noted. Testosterone was 318 ng/dL (Tanner stage I: 0-18), LH 3.2 mIU/mL (prepubertal: 0-0.3), DHEA-S 2 ug/dL (0-33), FSH 1.1 mIU/mL (prepubertal: 0-1), consistent with hypothalamic pituitary gonadal (HPG) axis activation. Given previous reports of prolonged but self-resolving “mini-puberty of infancy” in AHC, observation was initially chosen. At 12 months of age the bone age was consistent with the Greulich and Pyle 17 months standard. At 13 months of age testosterone remained elevated, therefore based on others’ reported experiences we increased HC from 8 to 15 mg/m2/day and noted a decrease in testosterone to 104 ng/dL within 5 days. HC was further increased to 18 mg/m2/day for 15 days, however testosterone increased to 270 ng/dL, therefore decision was made to treat with Lupron Depot. Conclusions: Historically, hypogonadotropic hypogonadism has been observed in 76% of adolescent patients with AHC who have alterations in NR0B1. CPP has been infrequently described in AHC, and the natural history and management of CPP in this setting is not established. CPP in AHC does not seem to correlate with any particular functional domain of DAX1, because previously reported NR0B1 variants associated with CPP, and this case’s, are dispersed across the gene. The course of our patient suggests multiple underlying mechanisms, including early HPG axis activation as well as the possibility of ACTH dependent precocious puberty. Our observations may contribute to the understanding of factors influencing normal and abnormal puberty in infants. Increased awareness of the possibility of CPP in AHC will aid clinicians in the earlier clinical and laboratory detection of this complication. Presentation: 6/1/2024