The Journal of clinical endocrinology and metabolism · 2026
Longitudinal Characterization and Sonographic Staging of Testicular Adrenal Rest Tumors.
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Vaid Sonal, Kulkarni Sarah, Marko Jamie, Sinaii Ninet, Sukin Charles, Burkardt Deepika, Eustace Quentin, Mallappa Ashwini, Merke Deborah P
Аннотация
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.
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.