Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Buenos Aires, Argentina.
Front Endocrinol (Lausanne). 2021 Dec 20;12:770782. doi: 10.3389/fendo.2021.770782. eCollection 2021.
Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.
性发育障碍（DSD）是胎儿性分化过程中出现的异常，导致染色体性别与性腺和/或内外生殖器性别不一致。影响肾上腺功能的先天性疾病可能与 46,XX 和 46,XY 个体的 DSD 有关，但发病机制不同。在 46,XX 病例中，肾上腺类固醇生成障碍导致生殖器异常，而在 46,XY 患者中，DSD 是由于相关睾丸功能障碍引起的。原发性肾上腺功能不全的特征是皮质醇分泌减少和 ACTH 过度产生，这是常见的。此外，患者可能表现出醛固酮缺乏，导致盐耗竭危象，这可能危及生命。ACTH 的营养作用会引起先天性肾上腺增生（CAH）。导致 46,XX DSD 的肾上腺类固醇生成缺陷是 21-羟化酶缺乏，这是最常见的，还有 11β-羟化酶缺乏。StAR 缺陷导致的脂质性先天性肾上腺增生和细胞色素 P450scc 和 P450c17 缺乏导致 46,XY 新生儿 DSD。SF1 突变也可能导致 46,XY 个体的肾上腺和睾丸功能衰竭，导致 DSD。最后，3βHSD2 或 POR 的活性受损可能导致 46,XX 和 46,XY 个体的 DSD。本文对上述疾病的病理生理学、临床表现和治疗进行了批判性评价，特别关注最新的生物标志物和治疗进展。
