Adrenal Rest Tumors and the clinical course of gonadal dysfunction in adult men with Congenital Adrenal Hyperplasia caused by 21-Hydroxylase Deficiency: A single-center experience with long-term follow-up.

Abstract

Purpose: Testicular adrenal rest tumors (TARTs) are among the most important long-term complications in males with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to evaluate the prevalence, clinical characteristics, and hormonal profile associated with TARTs in adult men with CAH.

Methods: This retrospective cohort study included 23 adult male patients with CAH due to 21-hydroxylase deficiency. Clinical, biochemical, genetic and radiological data, including treatment and treatment response, were retrospectively collected, and CYP21A2 genotypes were classified into severity groups. Clinical, laboratory and genetic characteristics were compared between patients with and without TARTs.

Results: Among 23 patients, TARTs were detected in 11 (48%). Patients with TARTs had significantly higher concentrations of ACTH (384 ng/L) and 17-OHP (96 ng/mL) (both p < 0.001). Of the patients with TARTs, 82% had the salt-wasting phenotype, while 18% had the simple-virilizing phenotype. Group Null genotypes were more frequent in patients with TARTs (90% vs. 20%, p = 0.005). Bilateral testicular involvement was observed in 9/11 patients (82%). Median age at diagnosis of CAH was significantly lower in patients with TARTs [0 (0-44) years] than in those without TARTs [7 (0-63) years] (p = 0.021). No consistent pattern was observed between changes in glucocorticoid therapy and TART regression.

Conclusion: TARTs are a common complication in adult men with CAH and are associated with impaired testicular function. TARTs were more frequent among patients with severe genotypes and/or inadequate disease control. Early and regular testicular ultrasound screening may facilitate timely diagnosis and help preserve fertility potential.