关键词: 肾上腺性征异常综合征, 遗传基础, 分子机制, 个体化治疗, 精准医疗, 生物标志物

Abstract: Adrenal Genital Syndrome (AGS) is a rare endocrine disorder characterized by impaired adrenalsteroid hormone synthesis.It primarily encompasses two subtypes:congenital adrenal hyperplasia (CAH) and adrenocortical tumors that secrete sex hormones,both of which exhibit significant genetic heterogeneity and phenotypic variability.Over 95% of CAH cases are attributed to 21-hydroxylase deficiency (21OHD CAH),resulting from mutations in the CYP21A2 gene.In the East Asian population,c.293-13C/A>G and c.955C>T represent prevalent mutation hotspots.These mutations disrupt cortisol and aldosterone biosynthesis,leading to elevated adrenocorticotropic hormone (ACTH) levels and excessive adrenal androgen production.Clinically,this manifests as either the classic form-presenting with neonatal salt wasting crisis and disorders of sex development or the non-classic form,associated with symptoms of hyperandrogenism.Sex hormone secreting adrenal tumors are typically driven by oncogene activation and tumor suppressor gene inactivation,characterized by autonomous sex hormone secretion.Diagnosis relies on a comprehensive approach integrating hormonal assessments (e.g.,17 hydroxyprogesterone,11-oxygenated androgens),molecular genetic testing (including sequencing of genes such as CYP21A2),and imaging studies.Conventional management includes glucocorticoid and mineralocorticoid replacement therapy for CAH and surgical resection for tumors;however,challenges persist,including suboptimal mimicry of physiological hormone rhythms and difficulties in dose titration.Recent advances have enabled more individualized therapeutic strategies,including modified-release hydrocortisone (Efmody),pediatric-specific formulations (Alkindi),hypothalamic-pituitary-adrenal (HPA) axis modulators (e.g.,CRF-1 receptor antagonists),CYP17A1 inhibitors (e.g.,abiraterone acetate),and emerging curative approaches such as cell-based and gene therapies.Bilateral adrenalectomy may be considered for patients refractory to medical treatment.

Key words: adrenogenital syndrome, genetic basis, molecular mechanism, individualized treatment, precision medicine, biomarker