Male Habitus Research Articles

MALE PSEUDOHERMAPHRODITISM WITH GYNAECOMASTIA DUE TO TESTICULAR 17-KETOSTEROID REDUCTASE DEFICIENCY

SUMMARY A 28-year-old male pseudohermaphrodite with gynaecomastia was raised as a female until the age of 17 years, at which time he developed masculine features (deepening of the voice, development of facial hair, male distribution of body hair and male body habitus) and assumed a male gender role. He had a small phallus with perineal urethra, absence of labioscrotal fusion, presence of vaginal pouch and undescended testes. The testicular biopsy showed hyalinization of the tubular basement membrane, lack of spermatogenesis and hyperplastic Leydig cells. Baseline peripheral plasma studies showed androstenedione concentrations ten times normal, low testosterone, elevated oestrone and elevated gonadotrophins. The in vitro incubation of testicular tissue showed no significant conversion of androstenedione to testosterone. However, two types of peripheral tissues, skin fibroblasts and erythrocytes, had a normal conversion, as did the body overall as measured by the technique of androstenedione constant infusion. These studies demonstrate that the 17-keto-steroid reductase deficiency of the patient was limited to the testes.

MALE PSEUDOHERMAPHRODITISM DUE TO STEROID 5α-REDUCTASE DEFICIENCY

PETERSON, RALPH E.; IMPERATO-MCGINLEY, JULIANNE; GAUTIER, TEOFILO; STURLA, ERASMO Author Information

Male pseudohermaphroditism due to steroid 5α-reductase deficiency

A new inherited form of male pseudohermaphroditism has been investigated in a pedigree of 24 families with 38 affected males. At birth, the affected males (46 XY) have a clitoral-like phallus, bifid scrotum and urogenital sinus. The testes are in the inguinal canals or labial-scrotal folds. The Wolffian structures are normally differentiated; there are no Mullerian structures. At puberty a muscular male habitus develops with growth of the phallus and scrotum, voice change and no gynecomastia. The subjects have erections, ejaculations and a libido directed towards females. They have decreased body hair, a scant to absent beard, no temporal hair line recession and a small prostate. Testicular biopsy reveals a normal testis. The mean plasma T levels in affected adults are significantly higher, and the mean plasma DHT levels are significantly lower when compared to those in normal subjects. The plasma T:DHT ratios range from 35 to 84 compared to 8 to 16 in normal subjects. After the administration of hCG, the T:DHT ratios in affected male children range from 74 to 162 compared to 3 to 26 in the control subjects. In affected adults, mean plasma LH and FSH levels are significantly higher than in normal subjects. In the affected subjects, the metabolic clearance rates of T and DHT are normal, but the conversion ratio of T to DHT is less than 1 per cent. The endogenous mean urinary E:A and E-OH:A-OH ratios, and the urinary E:A and E-OH:A-OH ratios after the infusion of radioactive T are significantly higher than in normal males. Inheritance is autosomal recessive with some sibling sisters showing the same biochemical defect, and obligate carrier parents showing an intermediate defect. These data support our thesis that the defect in these male pseudohermaphrodites is secondary to decreased steroid Δ 4-5α-reductase activity. The affected subjects provide a clinical model for delineating the roles of T and DHT in sexual differentiation and development. This entity also demonstrates an inherited disorder of steroid metabolism in which the basic enzyme deficiency resides in the target tissues.