Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia: 6 years of follow-up

Abstract

Background Testicular adrenal rest tumors (TARTs) leading to primary gonadal failure are the main etiology of infertility in congenital adrenal hyperplasia (CAH). We aimed at identifying the evolution of TART and related findings in young CAH patients. Methods Twelve male patients (3–23 years old) with 21-hydroxilase deficiency (11 with classic salt-wasting form) were included. Testicular ultrasonography (US) was performed in two moments, by a single blinded specialist in pediatric diagnostic imaging. Tumor progression was classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The clinical and laboratory data were retrieved from medical records. Serum 17-OH-progesterone (17OHP) and androstenedione concentrations were evaluated during the whole period of follow-up, from the CAH diagnosis. A logistic regression model with repeated measures was developed for the analysis. Results The prevalence of TART was 41.6% (n = 5) in the initial US evaluation and 66.6% (n = 8) after 6 years of follow-up. Tumor progression was detected in 4 of the 5 patients, and 1 presented with a stable tumor. Three patients presented with new tumors in the second evaluation. Most of the patients (n = 11) were pubertal, including a 7-year-old child with TART who presented with central precocious puberty. At regression analysis, it was observed that an inadequate hormonal control led to a 16 times greater chance of a patient to present with TART (OR = 16.08; confidence interval [CI] 95% = 2.38–108.81; p = 0.004). Conclusions We found a high prevalence of progressive TART in young pubertal subjects. US testicular screening should help in improving therapeutic optimization in CAH patients to reduce future impairment in fertility.

Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues

“…Unsupervised hierarchical clustering using the complete clustering method showed that TART was most similar to either adult (adrenal-and testis) tissue, and least similar to either fetal (adrenal and testis) tissue ( Figure 2A). Ten TART samples (TART1-5,8-12) from CAH patients and two TART samples that were removed from a patient with Cushing's Disease (Cushing-TART (CT)) were clustered together with adult adrenal tissue, whereas four TART samples (TART6, 7,13,14) were clustered together with adult testis tissue. Fetal adrenal and testis tissues were clustered separately.…”

“…ACTH is considered to be a growth promoting factor of TART, as the growth of TART is associated with poor hormonal control (11) and correlates with increased ACTH levels (12,13). Besides, intensifying glucocorticoid treatment is sometimes effective in reducing tumor size, most likely due to the suppressing effects on ACTH levels (12,(14)(15)(16).…”

Testicular Adrenal Rest Tumors in Patients with Congenital Adrenal Hyperplasia: A Case Series

“…Reported prevalence of TARTs varied between 14% to 86% in the literature. [1][2][3][4][5][6][7][8][9][10][11] This variation is related to age range of the patient population, the severity of the disease and the method of detection. In studies included only children, the prevalence was reported between 10% to 70%.…”

“…1,19 In poorly controlled patients with CAH, high ACTH levels cause proliferation of undifferentiated adrenal cells which induces the formation of TART in rete testis. 3 Optimization of steroid treatment is recommended to prevent disease progression. However, suppression of ACTH secretion is not always successful in reducing tumor size, and even well-controlled CAH patients with normal or suppressed plasma ACTH levels have testicular adrenal resting tumors.…”

“…Common adrenogenital primordium-derived undifferentiated adrenal cells are thought to remain in the testicular parenchyma and lead to tumor formation by chronic ACTH stimulation. 3,4 Poor hormonal control seems to be associated with TART. Decreasing ACTH levels with high-dose glucocorticoid therapy causes shrinkage in testicular adrenal rest tumors.…”