A practical approach to diagnosis and treatment in children with primary adrenal insufficiency.

Primary adrenal insufficiency (PAI) is a rare, life-threatening condition. In children, PAI is associated with several heterogeneous conditions, both genetic and acquired, although inherited disorders are more common. The most frequent cause is congenital adrenal hyperplasia (CAH); however, several other non-CAH conditions have been recently identified. Given the wide range of potential underlying conditions, a personalized, stepwise diagnostic approach is essential. Early recognition and treatment are critical to prevent morbidity and mortality; however, diagnosis in childhood remains challenging, and delays are common. In addition, the therapeutic strategies are not always able to replicate the natural cortisol rhythm, thus leading to increased risk of suboptimal treatment and unfavorable outcomes. Substantial progress over the past decades has yielded new insights into the genetic etiology, outcome, and therapeutic strategies for PAI in childhood. This review highlights key recent advancements and their clinical implications, exploring future directions in the management and treatment of pediatric PAI.