Persistent testicular delta5-isomerase-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) deficiency in the delta5-3beta-HSD form of congenital adrenal hyperplasia.

Abstract

A B S T R A C T A partial testicular defect in testosterone secretion has been documented in a pubertal male with a congenital adrenal hyperplasia due to hereditary deficiency of the A5-isomerase-3fi-hydroxysteroid dehydrogenase enzyme complex (AY-3j-HSD). Diagnosis of the enzymatic defect is based on the clinical picture of ambiguous genitalia and salt-losing crisis in infancy, together with high urinary A5-pregnenetriol and plasma dehydroepiandrosterone when the patient was taken off replacement corticoid treatment. No hormonal response to ACTH or salt deprivation was demonstrable. In addition, in vivo studies revealed a partial enzymatic defect in the testis. Although plasma testosterone was low-normal (250 ng/100 ml), plasma A5-androstenediol was markedly elevated and rose to a greater extent than testosterone after human chorionic gonadotropin administration. In vitro testicular incubation studies suggested a testicular A5-3%-HSD enzyme defect with less A4 products formed from A5 precursors than in a control testis. Histochemical studies of the testis were also consistent with this defect. Testicular biopsy revealed spermatoAn abstract of a portion of this work has appeared in Pediatr. Res.

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

“…Treatment resulted in testicular growth and pubertal advancement, but effect on gynecomastia was not further described. In HSD3B2 deficiency, development of secondary sexual characteristics and marked gynecomastia at puberty has been described in 46,XY DSD individuals and seems not to correlate with the severity of enzyme deficiency (Table 3) (2,5,6,7,8,9,10,11,12,13,14,19,20,22). Gynecomastia may rather correspond to peripheral precursor conversion to estrogens which depends on accuracy of replacement therapy and peripheral HSD3B1 activity.…”

“…Case Report M-A Burckhardt and others Histology of HSD3B2 deficiency 173:5 K6 described pubertal development (Table 3) (2,5,6,7,8,9,10,11,12,13,14,19,20). Remarkably, the adrenal phenotype was mostly more severe than the DSD phenotype, and all subjects spontaneously virilized at puberty (when not gonadectomized).…”

“…Case Report M-A Burckhardt and others Histology of HSD3B2 deficiency 173:5 K8 Table 4 (8,9,12,13,14,16,23,24,25,26,27,28,29,30,31,32,33,34,35,36). For spermatogenesis and thus fertility, the few data available suggest that it varies between different androgen biosynthetic defects as well as between individuals carrying defects in the same gene.…”

“…We found few longitudinal studies reporting on puberty and early adulthood of 46,XY patients with HSD3B2 deficiency (5,6,7,8,9,10,11,12,13). Moreover little is known about fertility (2,5,6,9) and virtually nothing about gonadal malignancy risk in patients with HSD3B2 deficiency, although some data on testis histology are reported (8,9,12,13,14).…”

“…Moreover little is known about fertility (2,5,6,9) and virtually nothing about gonadal malignancy risk in patients with HSD3B2 deficiency, although some data on testis histology are reported (8,9,12,13,14). An adrenal rest tumor has been visualized by ultrasound in an 18-year-old 46,XY DSD patient with a HSD3B2 mutation, but no biopsy was performed (5).…”