Urinary androstanediol and testosterone in adults.

Data are presented on the daily urinary excretion of androstanediol and testosterone in healthy adults using a sensitive radioligand assay. In nine men, the average urinary androstanediol (79 mug/day) was not significantly different from the urinary testosterone (84 mug/day). However, in women the average values of urinary androstanediol excretion (12 mug/day) were significantly higher than the urinary testosterone (4.2 mug/day). In each of the females, the urinary androstanediol was greater than the urinary testosterone. The data do not support the hypothesis that the daily urinary androstanediol excretion is a measure of the 5alpha-reduction of testosterone in androgen target tissues.

Prepubertal diagnosis of steroid 5 alpha-reductase deficiency.

The diagnosis of 5 alpha-reductase deficiency was proven in two prepubertal patients with male pseudohermaphroditism (MPH). Both had a 46-XY karyotype and were reared as females; one child had been castrated in infancy. Clitoromegaly, urogenital sinus, and short vaginal pouch were present in both; inguinal gonads were palpable in one. The diagnosis was made biochemically by observing characteristic changes in five parameters: 1) abnormally high testosterone to dihydrotestosterone (T:DHT) ratio after hCG stimulation (35 and 53 vs. normal, 11 +/- 3), 2) abnormally high 5 beta-T metabolites in urine (8.1 and 6.0 vs. normal, less than 1),3) deficient conversion of T to DHT during [3H] T infusion (0.3 and 0.4% vs. normal, 5.3 +/- 3), 4) deficient conversion of [14 C] T to 5 alpha-reduced metabolites by nongenital skin fibroblasts (2.2 and 1.9 pmol/microgram DNA/nmol substrate vs. 68.4+/- 7.8 Pmol/microgram DNA/nmol substrate in normal controls), and 5) deficient conversion of [14C]T to DHT in genital skin slices. The fact that this syndrome represents a defect in T metabolism rather in in T binding is demonstrated by the observation that binding of [3H]DHT to cytosol of skin fibroblasts was normal (4.2 dpm/micrograms DNA vs. normal male values of 3.7 +/- 0.64). Thus, the present report suggests that 5 alpha-reductase deficiency can be diagnosed during childhood and even after castration by metabolic studies of nongenital skin fibroblasts and determination of the conversion ratio of [3H]T to [3H]DHT in plasma.

Presence of H-Y antigen and testis in 46, XX true hermaphroditism, evidence for Y-chromosomal function.

Endocrinologic and serologic studies of a 2-year-old child with the chromosomal complement 46,XX and ambiguous genitalia suggested the preoperative diagnosis of true hermaphroditism. Urinary and serum androgen production in response to human chorionic gonadotrophin was in the range expected for normal males, implying presence of cryptic testicular tissue. Moreover, detection of H-Y antigen, a cell surface component associated with testicular differentiation and coded or regulated by a Y-chromosomal gene, indicated presence of Y-chromosomal material. The diagnosis of true hermaphroditism was confirmed at surgery. Assuming a constant association of H-Y antigen and testicular differentiation is established, human H-Y serology may be an important adjunct to the endocrinologic evaluation of intersex patients. Our studies support the interpretation that a Y-chromosomal translocation too small for cytologic detection accounts for testicular differentiation in 46,XX true hermaphroditism. Expression of H-Y antigen remained positive after castration.

Elevated urinary testosterone and androstanediol in precocious adrenarche.

Using a newly devised radioligand method for the simultaneous determination of urinary testosterone (T) and androstanediol (Adiol) nine girls with precocious adrenarche were evaluated. In the base-line state average urinary T excretion (1.29 mug/24 hr) and Adiol excretion (1.33 mug/24 hr) were significantly elevated when compared with 15 age-matched controls (0.3 and 0.33 mug/ 24 hr, respectively, P less than 0.001 for both). Adrenocorticotropic hormone (ACTH) infusion performed in five patients with precocious adrenarche produced at least a 50 greater than increase in urinary T excretion in all and a similar increase in Adiol excretion in four of five patients. Dexamethasone administration in the same five patients produced a 25 greater than fall in urinary T excretion in all and a comparable fall in Adiol in four.