Adrenal Hypoplasia: A Diagnostic and Clinical Challenge

Adrenal insufficiency can be life-threatening and results from inadequate secretion of hormones by the adrenal cortex. In pediatric patients, the most common cause is congenital adrenal hyperplasia due to 21-hydroxylase deficiency. We present a clinical case of a 17-year-old male. During the neonatal period, he experienced a salt-wasting crisis with shock, hyponatremia, metabolic acidosis, and elevated adrenocorticotropic hormone (ACTH) levels, with normal 17-hydroxyprogesterone. Hydrocortisone and fludrocortisone were initiated. Ten months later, genetic testing for the <i>CYP21A2</i> gene was normal, and 17-hydroxyprogesterone levels were low, prompting the tapering of medication. However, another salt-wasting crisis led to the resumption of treatment. The patient presented a clear need for high doses of glucocorticoids to maintain symptomatic control. Genetic testing revealed a deletion in the <i>CSNK2A1</i> gene, linked to Okur-Chung syndrome, along with a pathogenic <i>NR0B1</i> variant, confirming adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Hormone replacement and testosterone supplementation improved growth and pubertal development. The case improves our understanding of the phenotypic range and diagnostic challenges associated with NR0B1-related adrenal hypoplasia. Besides, the concurrent diagnosis of a second genetic disorder created additional challenges for both diagnoses. It emphasizes the importance of comprehensive clinical, biochemical, and genetic assessment to avoid misdiagnosis and ensure appropriate management strategies for complex endocrine disorders.