Prepubertal male pseudohermaphroditism due to 17-ketosteroid reductase deficiency: diagnostic value of a hCG test and lack of HLA association.
Most patients with male pseudohermaphroditism (MPH) due to 17-ketosteroid reductase (17-KSR) deficiency were diagnosed at or after puberty when significant virilization occurred. We report 2 prepubertal sibs (Case 1, 4 yr and Case 2, 10 yr) unambiguously raised as females, with clitoral enlargement, separate urethral and vaginal orifices and gonads palpable at the inguinal canal bilaterally. Basal serum LH, FSH, 17-hydroxyprogesterone, testosterone (T), dihydrotestosterone and dehydroepiandrosterone (DHEA) were normal for age. delta 4-Androstenedione (delta 4-A) was slightly elevated in Case 2 but nondiagnostic. Steroid measurements after human chorionic gonadotropin (hCG) stimulation were compared with those of boys with male external genitalia submitted to the same hCG protocol: peak T was subnormal (Case 1, 80, Case 2, 91, vs normal 329 +/- 129 ng/dl, mean +/- 1SD), peak delta 4-A elevated (Case 1, 477, Case 2, 264, vs normal 44 +/- 26 ng/dl) resulting in an abnormally elevated delta 4-A/T ratio (Case 1, 6.0, Case 2, 2.9, vs normal 0.12 +/- 0.09) and establishing the diagnosis of 17-KSR deficiency. This diagnosis was confirmed in vitro by minimal T production when testicular tissue of both patients was incubated with tritiated delta 4-A. The 2 sibs did not share a single haplotype for the HLA complex indicating lack of association between HLA and the locus of the gene for 17-KSR. In conclusion, in 2 sibs with MPH the subnormal T and elevated delta 4-A response to the hCG test indicated the diagnosis of 17-KSR deficiency followed by orchiectomy to avoid later virilization at puberty.
Arnhold
I J
IJ
Department of Medicine, Hospital das Clinicas, University of Sao Paulo School of Medicine, Brazil.
Mendonça
B B
BB
Diaz
J A
JA
Nogueira
C
C
Batista
M C
MC
Madureira
G
G
Oliveira
D
D
Nicolau
W
W
Bloise
W
W
D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008297:Male; D012801:Sibling Relations; D013737:Testis / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D006063:Chorionic Gonadotropin; D006680:HLA Antigens; D015067:17-Hydroxysteroid Dehydrogenases