46,XX DSD: the masculinised female.
The 46,XX disorders of sex development (DSDs) cause virilisation or masculinisation of the female foetus. The final common pathway of all 46,XX DSDs is excess dihydrotestosterone (DHT) or potent foreign androgen in the genital tissue during the critical period of sexual differentiation. Whereas the foetal testis is source of androgen in the male, it is the foetal adrenal that produces the DHT precursors in the female. By understanding the principles of human steroid biosynthesis, the pathogenesis of each disorder may be logically deduced, and treatment strategies are rationally constructed. In practice, however, therapies for many of these diseases are fraught with complications and caveats, and current approaches leave much room for improvement. This review discusses these diseases, their pathogenesis and approaches to therapy. We emphasise areas where improved treatments are sorely needed.
Auchus
Richard J
RJ
Division of Endocrinology and Metabolism, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8857, United States. Richard.Auchus@UTSouthwestern.edu
Chang
Alice Y
AY
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000293:Adolescent; D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics / Q000503:physiopathology; D000328:Adult; D054882:Antley-Bixler Syndrome Phenotype / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D002648:Child; D003366:Cosyntropin; D003687:Dehydroepiandrosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D005260:Female; D023961:Gonadal Dysgenesis, 46,XX / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D012733:Sex Differentiation; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D014770:Virilism / Q000209:etiology* / Q000378:metabolism
D013256:Steroids; D013196:Dihydrotestosterone; D003366:Cosyntropin; D003687:Dehydroepiandrosterone; D019326:17-alpha-Hydroxyprogesterone; D013255:Steroid 21-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase