Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: an update.

Abstract

Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders characterized by enzyme deficiencies thatimpair adrenal steroidogenesis, most commonly due to 21-hydroxylase deficiency. The biochemical defects in CAH translate to a spectrumof clinical consequences, which include adrenal insufficiency, genital ambiguity or disordered sex development, infertility, short stature,and an increased risk of metabolic syndrome during adolescence and adulthood. The severity and clinical features of CAH vary dependingon the enzymatic defect, residual enzymatic activity, the age of presentation, and genotype. This review comprehensively covers the genetic background, classification, and clinical spectrum of CAH, including classical and non-classical forms. We discuss the importance and implementation of neonatal screening programs for early diagnosis and intervention. Specialattention is given to differences in treatment approaches between children and adolescents, highlighting the challenges of optimizingglucocorticoid and mineralocorticoid therapy across developmental stages. Furthermore, we present emerging novel pharmacologicalagents currently in clinical trials aimed at improving disease management. The review also addresses potential complications associatedwith CAH, such as metabolic syndrome, cardiovascular risks, and bone health issues. Emphasizing a patient-centered approach, wehighlight the critical role of experienced endocrinologists in delivering individualized care to improve long-term outcomes. Our review summarizes the current knowledge, aims to guide clinicians in evidence-based management and highlights ongoing research into innovativetherapies for CAH.