Longitudinal Characterization and Sonographic Staging of Testicular Adrenal Rest Tumors.

Testicular adrenal rest tumors (TART) frequently develop and are the most common cause of male infertility in classic congenital adrenal hyperplasia (CAH). Little is known about the natural course. We aimed to investigate age of onset, associated factors, and characterize the sonographic natural history of TART in males with classic CAH followed prospectively from childhood to adulthood. Longitudinal study of clinical and hormonal data and serial scrotal ultrasounds performed every 6 months during childhood and annually in adulthood. Survival analysis and longitudinal models were used to determine age of TART onset and factors associated with TART progression. 783 ultrasounds from 36 males were evaluated. 27 (75%) developed TART, mean age of onset 13.6 ± 4.9 years, with ∼22% risk before age 10. TART presence was associated with elevated ACTH, 17-OHP, androstenedione, and PRA, younger age at diagnosis, salt-wasting (SW) phenotype and null/In2G mutations. Multivariable analysis revealed SW phenotype [OR: 6.83, 95% CI (2.36-19.77); P<0.001], treatment with higher hydrocortisone dose equivalence [OR: 1.10, 95% CI (1.03-1.18); P=0.006], and elevated ACTH [OR: 1.0011, 95% CI (1.0005-1.0017); P<0.01] increased risk of TART at any given visit. Of 19 patients with TART at last visit, hydrocortisone equivalent was 16.0 ± 7.9 mg/m²/day, lower than 21.3 ± 7.5 mg/m²/day observed in patients whose TARTs resolved. Serial sonograms showed a characteristic pattern of TART progression from a single hypoechoic nodule to multiple hypoechoic nodules, to a single conglomerate mass near the mediastinum testis. TART formation in CAH is frequently found in pre-pubertal boys, with a characteristic pattern of development resulting in a proposed radiologic staging. Pediatric screening is recommended, especially in those with a SW phenotype/genotype.