ESPE Abstracts

Background: Late identification of male patients with congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency (21OHD) can increase the risk of developing a benign tumor near the mediastinum testes called testicular adrenal rest tumors (TART), that can cause infertility. However, these long-term consequences of 21OHD have not yet been studied in Indonesia.

Objective: This study aims to elucidate the prevalence of TART and the association of bone age advancement, hormonal profile, and genotype with TART in boys with 21OHD in Indonesia.

Methods: A cross-sectional study on twenty boys aged 0-18 years old with biochemically confirmed 21OHD was conducted. Medical history, physical examination, bone age data, biochemical investigation, genotype analysis, and scrotal ultrasonography (US) data were evaluated. The biochemical investigation consists of the 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, inhibin B, FSH, and LH concentration. Furthermore, we calculated the A/T ratio by dividing androstenedione with testosterone concentrations.

Results: In our center, 131 patients were diagnosed with CAH, of whom 23 (17.6%) patients had a 46,XY karyotype. Two of these patients were deceased, and one was lost to follow-up before TART screening, leaving a total of 20 included patients. TART was found in 25% (n = 5/20) of the patients with a median age of 9.33 (range: 5.75-17.42) years old, versus 4.83 (range: 0.92-13.00) years old in the non-TART group (P =0.040). In total, 80% (4/5) of the TART patients was classified in pubertal stage, compared to 13.3% (2/15) in those without TART (P =0.014). Patients with TART had signs of poor hormonal control: a significantly higher bone age advancement [75.50 (19-87) months old vs. 4.00 (-23-53) months old, P =0.008], hyperpigmentation [n = 4/5 (80%) vs. n = 1/15 (6.7%), P =0.05], and elevated androstenedione concentrations (P =0.029) compared to those without TART. Significantly lower fludrocortisone dose in patients with TART [0.050 (0.025-0.050) mg/day vs. 0.075 (0.025-0.100), P =0.046] were observed. All patients had pathogenic variants of the CYP21A2 gene associated with 0% or 0-1% residual enzymatic activity, with the most common pathogenic variants in the TART group being R356W/del. There was no association between the concentration of 17-OHP, testosterone, inhibin B, FSH, or LH and TART, nor for the A/T ratio.

Conclusion: TART were present in 25% of Indonesian boys with 21OHD. Factors associated with TART are pubertal age, bone age advancement, hyperpigmentation, and elevated androstenedione concentration, confirming the increased risk of poorly controlled 21OHD patients to develop TART.

Keywords: Testicular Adrenal Rest Tumors, Congenital Adrenal Hyperplasia, 21 Hydroxylase Deficiency, Screening, Indonesia