TY - JOUR

T1 - Prepubertal and pubertal gonadal morphology, expression of cell lineage markers and hormonal evaluation in two 46,XY siblings with 17 beta-hydroxysteroid dehydrogenase 3 deficiency

AU - von Spreckelsen, Benedikte

AU - Aksglaede, Lise

AU - Johannsen, Trine Holm

AU - Nielsen, John E.

AU - Main, Katharina M.

AU - Jorgensen, Anne

AU - Jensen, Rikke Beck

PY - 2022

Y1 - 2022

N2 - Objectives: 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency results in insufficient biosynthesis of testosterone and consequently dihydrotestosterone. This is important for the fetal development of male genitalia. Thus, most 46,XY patients with 17 beta-HSD3 deficiency have a female appearance at birth and present with virilization at puberty. This study presents the differences in the clinical and hormonal data and analyses of gonadal characteristics in two siblings with 17 beta-HSD3 deficiency.Case presentation: Patient 1 presented with deepening of the voice and signs of virilization at puberty and increased serum levels of testosterone (T) of 10.9 nmol/L (2.9 SDS) and androstenedione (Delta 4) of 27 nmol/L (3.3 SDS) were observed. The T/Delta 4-ratio was 0.39. Patient 2 was clinically prepubertal at the time of diagnosis, but she also had increased levels of T at 1.97 nmol/L (2.9 SDS), Delta 4 at 5 nmol/L (3.3 SDS), and the T/Delta 4-ratio was 0.40, but without signs of virilization. Both siblings were diagnosed as homozygous for the splice-site mutation c.277+4A>T in intron 3 of HSD17B3. They were subsequently gonadectomized and treated with hormone replacement therapy. The gonadal histology was overall in accordance with pubertal status, although with a dysgenetic pattern in both patients, including Sertoli-cell-only tubules, few tubules containing germ cells, and presence of microliths.Conclusions: Two siblings with 17 beta-HSD3 deficiency differed in pubertal development at the time of diagnosis and showed marked differences in their clinical presentation, hormonal profile, gonadal morphology and expression of cell lineage markers. Early diagnosis of 17 beta-HSD3 deficiency appears beneficial to ameliorate long-term consequences.

AB - Objectives: 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency results in insufficient biosynthesis of testosterone and consequently dihydrotestosterone. This is important for the fetal development of male genitalia. Thus, most 46,XY patients with 17 beta-HSD3 deficiency have a female appearance at birth and present with virilization at puberty. This study presents the differences in the clinical and hormonal data and analyses of gonadal characteristics in two siblings with 17 beta-HSD3 deficiency.Case presentation: Patient 1 presented with deepening of the voice and signs of virilization at puberty and increased serum levels of testosterone (T) of 10.9 nmol/L (2.9 SDS) and androstenedione (Delta 4) of 27 nmol/L (3.3 SDS) were observed. The T/Delta 4-ratio was 0.39. Patient 2 was clinically prepubertal at the time of diagnosis, but she also had increased levels of T at 1.97 nmol/L (2.9 SDS), Delta 4 at 5 nmol/L (3.3 SDS), and the T/Delta 4-ratio was 0.40, but without signs of virilization. Both siblings were diagnosed as homozygous for the splice-site mutation c.277+4A>T in intron 3 of HSD17B3. They were subsequently gonadectomized and treated with hormone replacement therapy. The gonadal histology was overall in accordance with pubertal status, although with a dysgenetic pattern in both patients, including Sertoli-cell-only tubules, few tubules containing germ cells, and presence of microliths.Conclusions: Two siblings with 17 beta-HSD3 deficiency differed in pubertal development at the time of diagnosis and showed marked differences in their clinical presentation, hormonal profile, gonadal morphology and expression of cell lineage markers. Early diagnosis of 17 beta-HSD3 deficiency appears beneficial to ameliorate long-term consequences.

KW - 17 beta-hydroxysteroid dehydrogenase type 3 deficiency

KW - 17-ketosteroid reductase deficiency

KW - gonadal cell lineage markers

KW - gonadal morphology

KW - FAMILIAL MALE PSEUDOHERMAPHRODITISM

KW - DEHYDROGENASE-3 DEFICIENCY

KW - PHENOTYPIC VARIABILITY

KW - GYNECOMASTIA

KW - MUTATIONS

KW - DIAGNOSIS

KW - GENETICS

U2 - 10.1515/jpem-2021-0713

DO - 10.1515/jpem-2021-0713

M3 - Journal article

C2 - 35411763

VL - 35

SP - 953

EP - 961

JO - Journal of Pediatric Endocrinology and Metabolism

JF - Journal of Pediatric Endocrinology and Metabolism

SN - 0334-018X

IS - 7

ER -