Genetics and Pathophysiology of Congenital Adrenal Hyperplasia

The document from 2017 provides a comprehensive overview of Congenital Adrenal Hyperplasia (CAH), particularly the most common form, 21-hydroxylase deficiency (21-OHD). It explains that CAH is an autosomal recessive disorder with varying clinical features depending on the mutation, affecting 1:5,000 to 1:15,000 for classic forms and 1:1,000 for nonclassic CAH (NCAH). The pathophysiology involves impaired cortisol production, leading to excessive adrenal androgen production and symptoms such as ambiguous genitalia, dehydration, and hyperkalemia. The document also discusses the challenges in diagnosing NC-21-OHD due to symptom overlap with polycystic ovary syndrome (PCOS) and the complexity of the CYP21A2 gene, which has over 200 identified mutations. Treatment strategies are individualized, aiming for normal growth and symptom management, with hydrocortisone preferred for children and longer-acting glucocorticoids for adults. Prenatal dexamethasone treatment is controversial due to potential risks. The document concludes that patient outcomes are often suboptimal due to poor management, especially during the transition to adult care, and calls for improved diagnostic tools and hormone replacement regimens.