Congenital adrenal hyperplasia

摘要

Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the adrenal steroidogenic pathway. The most common type of congenital adrenal hyperplasia is due to steroid 21-hydroxylase (21-OHase, henceforth 21OH) deficiency. The rare, classic (severe) form caused by 21OH deficiency is characterised by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype. After the introduction of life-saving hormone replacement therapy in the 1950s and neonatal screening programmes in many countries, nowadays neonatal survival rates in patients with congenital adrenal hyperplasia are high. However, disease-related mortality is increased and therapeutic management remains challenging, with multiple long-term complications related to treatment and disease affecting growth and development, metabolic and cardiovascular health, and fertility. Non-classic (mild) forms of congenital adrenal hyperplasia caused by 21OH deficiency are more common than the classic ones; they are detected clinically and primarily identified in female patients with hirsutism or impaired fertility. Novel treatment approaches are emerging with the aim of mimicking physiological circadian cortisol rhythm or to reduce adrenal hyperandrogenism independent of the suppressive effect of glucocorticoids.