Individualizing Management of Infertility in Classic Congenital Adrenal Hyperplasia and Testicular Adrenal Rest Tumors

Abstract

Testicular adrenal rest tumors (TARTs) are a common cause of male infertility in patients with classic congenital adrenal hyperplasia (CAH). These tumors are located in the rete testis and can lead to impaired blood flow and functional impairment of seminiferous tubules. We describe restoration of fertility in a man with CAH and bilateral TARTs with use of lower-dose glucocorticoid therapy than previously described. A 28-year-old man with classic salt-wasting CAH presented with impaired fertility. Biochemical evaluation showed poor CAH control despite reported compliance with prednisone 5 mg every morning and fludrocortisone 50 μg twice daily. Semen analysis showed azoospermia. Testicular ultrasonography showed TARTs occupying 16% of total testicular volume. After 5 months of dexamethasone 250 μg at bedtime, total TART volume decreased 90%, biochemical control improved, and semen analysis showed a sperm count of 132 × 106 million per milliliter. The patient’s wife was confirmed to be pregnant 9 months after the initial visit and delivered a healthy full-term baby girl. The patient’s glucocorticoid therapy was changed to prednisone 3 mg twice daily, and 2 years later he continues to show adequate CAH control, stable TART volume, and normal semen analysis, and his wife is pregnant again. Management of CAH in men with TARTs needs to be individualized, and high-dose dexamethasone may not be indicated. The use of a long-acting glucocorticoid at typical recommended dosages can decrease TART size and reverse male infertility. Prednisone given once daily does not adequately control the ACTH-driven complications of CAH.

Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues

“…Therefore, the identified overexpressed genes and overrepresented processes might point towards the fibrotic processes in TART or breakdown and remodeling of surrounding ECM, allowing further growth of the tumor. The emergence of fibrosis may explain the unresponsiveness of TART to glucocorticoid treatment in CAH patients (5,19). Further research with regard to those processes is required, as they may represent interesting drug targets to prevent the progression of TART.…”

“…However, an association between (long-term) hormonal control and the development or size of TART is not observed in all association studies (17,18) and intensified glucocorticoid treatment does not result in tumor shrinkage in all cases (4). Longstanding tumors may become fibrotic (5), potentially explaining the tumors' loss of responsiveness to glucocorticoid treatment (19) and the lack of correlation between long-term disease control and TART size in some studies. A better understanding of those fibrotic processes is required to prevent glucocorticoid-unresponsiveness and progression of TART.…”

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

“…Similar to females with CAH, optimal control of adrenal androgen production represents the main approach to preserving fertility potential. Recovery of a normal sperm count in an azoospermic man following treatment with a long-acting glucocorticoid was recently reported [158], although the benefits and potential risks of this form of therapy remain unclear [24].…”

Testicular Adrenal Rest Tumours: fisiopatologia, diagnosi e trattamento

“…Eventuali vantaggi di un regime terapeutico a base di formulazioni long-acting di glucocorticoidi a dosaggi standard sono ancora oggetto di discussione, sebbene siano riportati in letteratura recenti casi di regressione tumorale e di ripristino della fertilità, evidenziando ulteriormente la necessità di un approccio terapeutico individualizzato per ciascun paziente [28].…”