Longitudinal Characterization and Sonographic Staging of Testicular Adrenal Rest Tumors.

CONTEXT: 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.

OBJECTIVE

We aimed to investigate age of onset and associated factors and characterize the sonographic natural history of TART in males with classic CAH followed prospectively from childhood to adulthood.

METHODS

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.

RESULTS

Seven hundred eighty-three ultrasounds from 36 males were evaluated. Twenty-seven (75%) developed TART; the mean age of onset was 13.6 ± 4.9 years, with ∼22% risk before age 10. TART presence was associated with elevated ACTH, 17-hydroxyprogesterone, androstenedione, and plasma renin activity, younger age at diagnosis, salt-wasting (SW) phenotype, and null/In2G mutations. Multivariable analysis revealed SW phenotype [odds ratio (OR): 6.83, 95% confidence interval (CI) 2.36-19.77; P < .001], treatment with higher hydrocortisone dose equivalents (OR: 1.10, 95% CI 1.03-1.18; P = .006), and elevated ACTH (OR: 1.0011, 95% CI 1.0005-1.0017; P < .01) increased risk of TART at any given visit. Of 19 patients with TART at last visit, the hydrocortisone dose 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.

CONCLUSION

TART formation in CAH is frequently found in prepubertal 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.