46,XY DSD due to impaired androgen production
- Berenice B. Mendonca, a,
, 
, - Elaine M.F. Costa, a,
- Alicia Belgorosky, b,
- Marco Aurelio Rivarola, b,
- Sorahia Domenice, a
- a Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
- b Servicio de Endocrinologia, Hospital de Pediatria Garrahan, Buenos Aires, Argentina
- Available online 10 June 2010
46,XY DSD due to impaired Leydig cell differentiation (LHCGR defects)
46,XY DSD due to testosterone-synthesis defects
46,XY DSD due to testosterone-synthesis defects
Testicular steroidogenesis defects
Altered steroidogenesis due to disrupted electron donor proteins
46,XY DSD due to defects in testosterone metabolism
References
Disorders of androgen production can occur in all steps of testosterone biosynthesis and secretion carried out by the foetal Leydig cells as well as in the conversion of testosterone into dihydrotestosterone (DHT).
The differentiation of Leydig cells from mesenchymal cells is the first walk for testosterone production. In 46,XY disorders of sex development (DSDs) due to Leydig cell hypoplasia, there is a failure in intrauterine and postnatal virilisation due to the paucity of interstitial Leydig cells to secrete testosterone. Enzymatic defects which impair the normal synthesis of testosterone from cholesterol and the conversion of testosterone to its active metabolite DHT are other causes of DSD due to impaired androgen production. Mutations in the genes that codify the enzymes acting in the steps from cholesterol to DHT have been identified in affected patients.
Patients with 46,XY DSD secondary to defects in androgen production show a variable phenotype, strongly depending of the specific mutated gene. Often, these conditions are detected at birth due to the ambiguity of external genitalia but, in several patients, the extremely undervirilised genitalia postpone the diagnosis until late childhood or even adulthood. These patients should receive long-term care provided by multidisciplinary teams with experience in this clinical management.
Keywords
- Leydig cell hypoplasia;
- LHCGR defects;
- Smith–Lemli–Opitz syndrome;
- testosterone-synthesis defects;
- 5α-reductase type 2 deficiency
Figures and tables from this article:
Fig. 1. A: External genitalia of a 46,XY patient with a complete form of Leydig cells hypoplasia due to inactivating mutation in LHCGR. B: Right testis slightly smaller than normal.
Fig. 2. Photomicrograph of a testis section of a 46,XY patient with complete form of Leydig cell hypoplasia. Seminiferous tubules contain just Sertoli cells and occasional immature germ cells. The interstitium contains a sparse cell population and no mature Leydig cells
Fig. 3. Presence of male ducts in a 46,XY patient with the complete form of Leydig cells hypoplasia due to inactivating mutation in LHCGR. A: Vas deferens, B: Epididymis duct.
Fig. 4. A cartoon of human foetal Leydig cell showing all steps involved in androgen production.
Fig. 5. Adrenal and testicular steroidogenesis.
Fig. 6. Adult 46,XY patient with 17β-HSD3 deficiency (A) before and after (B) masculinising genitoplasty.
Fig. 7. A Prepubertal 46,XY due to 5α-reductase 2 deficiency children with ambiguous genitalia, small phallus and bifid scrotum. B: Adult males with 46,XY DSD due to 5α-reductase 2 deficiency after masculinising genitoplasty.
Table 1. - Classification of 46,XY DSD due to impaired androgen production
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Copyright © 2009 Elsevier Ltd. All rights reserved.
