Case Report:clinical experience of bilateral giant pediatric Testicular adrenal rest tumors with 3 Beta-Hydroxysteroid Dehydrogenase-2 family history

Abstract

Background We reported a patient with Testicular adrenal rest tumors(TARTs) caused by congenital adrenal hyperplasia(CAH). TARTs occur frequently in CAH population with 21-hydroxylase deficiency(21-OHD). There are few reports of TARTs with 3β-hydroxysteroid dehydrogenase deficiency-2 (3β-2HSD).Furthermore,gaint TARTs are rarely mentioned in reported cases involving affected siblings. Case presentation A 14-year-old male patient was admitted by congenital adrenal hyperplasia with progressively increasing bilateral testicular masses.The Patient and his elder brother had been performed mutational and chromosome analysis and biopsy. Hormonal and anthropometric measurements were performed during endocrine treatments. We successfully performed surgery and excised two 83mm×46mm×44mm and 74mm×49mm×31mm tumors. Our pathology and immunochemistry tests have proven TARTs in patient. At first, both siblings received regular doses of hydrocortisone and fludrocortisones and tumor size regressed. During the one-year irregular intake due to Covid-19 pandemic, endocrine treatment became insensitive and tumor size slowly increased. The gene analysis reported two novel mutations C.776 C>T and C.674 T>A. The C.776 C>T is from father and has been reported. The C.674 T>A inherited from mother and cannot found in gene library and may related to TARTs. Conclusions This case illustrates inadequate hormone therapy could cause tumor enlargement. It is essential to seek for ultrasound examination once suspected scrotal mass occurred.It is necessary to adjust endocrine medicine or adopt surgery in refractory gaint TARTs. And presence of tunica vaginalis cavity may indicate the severity of TARTs in surgery.

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

“…We synthetized the studies published according to the mentioned methodology in Table 1 [ 5 , 22 , 25 , 26 , 27 , 31 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

“…Some patients with SW associated DSD with males (mostly 46,XY males and mild virilisation in some 46,XX females; these generally are less affected concerning the spectrum of DSDs). Most cases of ambiguous genitalia were found in male patients who were affected by undermasculinization and presented with hypospadias, embedded penis, micropenis, scrotum bifidum, cryptorchidism, and vaginal introitus [ 22 , 25 , 26 , 31 , 38 , 39 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 53 , 56 , 57 , 58 , 59 ]. Female patients had either normal genitalia or were mildly virilised (for instance, clitoromegaly) [ 22 , 25 , 26 , 31 , 38 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 53 , 56 , 57 , 58 , 59 , 61 ].…”

“…Most relevant endocrine assays are displayed in Table 2 (some of the patients were undergoing hormonal replacement) [ 22 , 25 , 26 , 27 , 31 , 38 , 39 , 40 , 41 , 43 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as a “novel pathogenic mutation” [ 5 , 22 , 25 , 26 , 27 , 31 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 52 , 53 , 54 , 57 , 58 , 59 , 60 , 61 ] ( Table 3 ).…”

“…For instance, c.674T > A (p.V225D) mutation was confirmed on a 9-year-old Chinese boy with maternal and paternal inheritance of the genetic defect (the condition affected his older brother, too) [ 27 ]. Yu L. et al described two novel mutations on a male subject: one with paternal inheritance—C.776 C > T—and the other from his mother—C.674 T > A —which might be responsible for the presence of bilateral TARTs [ 39 ]. Fanis P. et al, revealed a novel nonsense mutation—p.Lys36Ter (homozygosity, consanguineous parents)—in addition to a heterozygous status for CYP21A2 gene—p.Val281Leu [ 40 ].…”