8045 A Case Report of Primary Adrenal Insufficiency Due to a Novel Pathogenic Variant in NR0B1 (Dax 1) Gene

Abstract Disclosure: M.N. Lemos: None. G.D. Martins: None. J.R. Cicogna: None. N.M. Scalissi: None. J.V. Lima-Jr: None. Background: X-linked adrenal hypoplasia congenita caused by a pathogenic variant in NR0B1/DAX-1 is a rare inherited disorder. Patients with adrenal hypoplasia congenita are usually diagnosed with primary adrenal insufficiency in infancy or early childhood and usually present hypogonadotropic hypogonadism during adolescence. Clinical Case: Our male patient first presented with adrenal crisis at the age of 11 years, managed with glucocorticoids (prednisolone) and mineralocorticoids (fludrocortisone) in a local hospital at Bahia state, Brazil. He was referred to our reference service in Sao Paulo at the age of 14, in regular use of those medications. In this time, he brought some laboratorial analysis from the time of diagnosis, and it showed hyponatremia (sodium 99 mEq/L; NR 135 - 150) and hyperkalemia (potassium 6,7 mEq/L; NR 3,5 - 5), ACTH 23,2 pg/mL (NR < 45) and basal cortisol 6,6 mcg/dL (NR 5 - 18). In addition, we had from this time some additional laboratorial data from our admissional analysis, that found S-DHEA 10,1 mcg/dL (NR: 23,8 - 267,7), total testosterone 472 ng/dL (NR: 240 - 816), FSH 3,05 mUI/L (NR: < 10), LH 2,63 mUI/L (NR: <10), aldosterone 1,9 ng/dL (NR: 5 - 23) and renin > 500µIU/mL (NR: 2,8 - 39,9). Over the years, he started to present hyperpigmented skin lesions, due to primary adrenal insufficiency, resulting in great psychological suffering. We have screened hypogonadism many times during follow-up, but it was never found. The Genetics analysis by next generation sequence (NGS) identified in homozygosity, in gene NR0B1 (DAX1) on X chromosome, a variant of normality (chrX:30.309.248 C>T) were amino acid tryptophan was replaced by a stop codon. The patient does not have any brother, no other similar cases in the family and their parents deny consanguinity. Our case differs from others previously described because of the absence of associated hypogonadism, which is very common in NR0B1 variants. Clinical lesson/Conclusion: This case report shows that the absence of hypogonadism does not exclude the possibility of primary adrenal insufficiency caused by NR0B1(DAX 1) gene variants, and encourages genetic testing to patients living with this disease. Presentation: 6/2/2024