Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Division of Paediatrics, Unit for Paediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden.
Lancet. 2023 Jan 21;401(10372):227-244. doi: 10.1016/S0140-6736(22)01330-7. Epub 2022 Dec 8.
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.
先天性肾上腺皮质增生症是一组常染色体隐性遗传病，导致多种肾上腺类固醇生物合成途径中各种酶缺乏引起的复杂激素失衡。最常见的先天性肾上腺皮质增生症类型是由于类固醇 21-羟化酶（21-OHase，以下简称 21OH）缺乏所致。由 21OH 缺乏引起的罕见的经典（严重）形式的特征是危及生命的肾上腺危象，是导致具有 46,XX 核型的新生儿出现非典型生殖器的最常见原因。自 20 世纪 50 年代引入挽救生命的激素替代疗法和许多国家的新生儿筛查计划以来，患有先天性肾上腺皮质增生症的患者的新生儿存活率很高。然而，疾病相关死亡率增加，治疗管理仍然具有挑战性，与治疗和疾病相关的多种长期并发症会影响生长发育、代谢和心血管健康以及生育能力。由 21OH 缺乏引起的非经典（轻度）形式的先天性肾上腺皮质增生症比经典形式更为常见；它们在临床上被发现，主要在患有多毛症或生育能力受损的女性患者中被识别。新的治疗方法正在出现，目的是模拟生理昼夜皮质醇节律，或在不依赖于糖皮质激素抑制作用的情况下减少肾上腺雄激素过多症。
