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

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.

Congenital adrenal hyperplasia in men: classical form. Clinical case

Recently, in the foreign scientific literature there have been reports that boys and young men with the classic virile form of congenital adrenal hyperplasia or congenital dysfunction of the adrenal cortex as a result of inadequate glucocorticoid therapy in 21–28 % of cases have testicular adrenal rest tumors, which increases under the influence of excessive production of adrenocorticotropic hormone (ACTH). This benign formation up to 2 cm in diameter and larger is detected by palpation and ultrasound. The formations can press on the testicular tissue and lead to hypogonadism. Such individuals may have low testosterone levels due to decreased Leydig cell function. Testicular adrenal rest tumors usually decrease after treatment optimization. Unreasonable surgery is sometimes performed in suspected cancer. A clinical case is presented of the classic form of congenital adrenal hyperplasia, manifested itself in isosexual precocious puberty, cryptorchidism and testicular adrenal rest tumors rare, increased under the influence of excessive ACTH production as a result of inadequate glucocorticoid replacement therapy. Formations detected during ultrasound decrease when treatment is optimized. Observation of the patient in the dynamics showed that ones of the main diagnostic hormonal tests are blood levels of ACTH and 17-hydroxyprogesterone, which at the time of disease detection were excessively high. Continuous glucocorticoid replacement therapy maintains the level of these indicators within the reference values. Timely diagnosis of the nature of the pathology, constant corrective hormone therapy ensured the patient’s abi­lity to adapt to life and society in accordance with his status. Clinical mani­festations of hypocorticism and/or hyperandrogenism in the parents of our patient were not detected, which indicates autosomal recessive inheritance of congenital adrenal hyperplasia. In the future, it is important to provide genetic counseling to expectant parents, especially with manifestations of hyperandrogenism, to assess the possible development of such pathology in their offspring.

Production of 11-oxygenated androgens by testicular adrenal rest tumors

Context Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done. Objective Define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART. Participants and methods Steroids were measured in left (n=7) and right (n=4) spermatic vein- and simultaneously taken peripheral blood (n=7) samples from seven men with 21OHD and TART using liquid chromatography-tandem mass spectrometry. For comparison, we also measured the peripheral steroid concentrations in five adrenalectomized patients and twelve age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation. Results Compared to peripheral blood of 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11β-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11β-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone, and lower levels of A4 and 11OHA4 after ACTH stimulation compared to adrenal cells, indicating ACTH-induced production of testosterone in TART. Conclusion In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic- versus peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.

Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors

Testicular adrenal rest tumors (TART) are a common complication in male patients with classic 21-hydroxylase deficiency (21OHD). TART are considered to have steroid-producing properties and may contribute to the androgen excess in 21OHD patients. This study aims to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART. Steroids were measured in left (n=7) and right (n=4) spermatic vein- and simultaneously taken peripheral plasma (n=7) samples from seven men with 21OHD and TART using liquid chromatography-tandem mass spectrometry. In addition, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation. Compared to peripheral blood of 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cell-conditioned medium contained higher levels of testosterone, and lower levels of androstenedione and 11OHA4 after ACTH stimulation compared to adrenal cell-conditioned medium, indicating ACTH-induced production of testosterone in TART. TART cells also produced 11OHT after 48 h of ACTH stimulation. Thus, in patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vein- versus peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in-vitro results indicate that this metabolism is ACTH-sensitive.