Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management

Abstract

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21- hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000 there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in congenital adrenal hyperplasia with special attention to these new developments.

Disorders of Sex Development of Adrenal Origin

“…21OHD shows a wide spectrum of phenotypes, no longer representing a clear cut between the classic and non-classic forms, as historically reported, but depicting a continuum between both forms which depends on the remaining enzyme activity ( 15 , 18 ). Classic CAH is the most severe form, and it is currently the most common cause of DSD and of primary adrenal insufficiency during childhood ( 15 , 18 ).…”

24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency

“…Congenital adrenal hyperplasia (CAH) is a set of autosomal recessive defects in cortisol biosynthesis, and of these, 21-hydroxylase deficiency (21OHD) represents the most common form ( 1 , 2 ). The molecular spectrum of 21OHD is wide, ranging from absent or minimal 21-hydroxylase activity, to fully compensated enzymatic defects ( 3 ).…”

Long-Term Health Outcomes of Korean Adults With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

“…Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders characterized by defective steroidogenesis due to enzyme deficiency. The most common form of CAH, 21-hydroxylase deficiency, affects approximately 1:15,000 live births ( 1 , 2 ). A 21-hydroxylase deficiency results in glucocorticoid deficiency and an increase in pituitary adrenocorticotropin (ACTH) secretion, leading to adrenal androgen excess and adrenal hyperplasia.…”

“…Depending on disease severity, CAH due to 21-hydroxylase deficiency is classified into classic (salt-wasting and simple virilizing) and non-classic forms ( 1 ). The early diagnosis of 21-hydroxylase deficiency through newborn screening test using 17-hydroxyprogesterone (17-OHP) has decreased mortality and morbidity rates, leading to increased interest in improving long-term health outcomes in adulthood ( 1 , 2 ).…”