Testicular Tumors in Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Show Functional Features of Adrenocortical Tissue

Abstract

Context:In male patients with congenital adrenal hyperplasia (CAH), testicular adrenal rest tumors are frequently found that may interfere with gonadal function.Objective: Our objective was to determine steroid-producing features of testicular adrenal rest tumors. Design and Setting:The study is descriptive and took place at a university medical center. Patients:Eight adult CAH patients with bilateral testicular adrenal rest tumors were treated with testis-sparing surgery. Interventions:In all but one patient, spermatic veins were cannulated during surgery and blood samples collected to measure the adrenal-specific steroid 21-deoxycortisol (21DF) and 17-hydroxyprogesterone (17OHP) and androstenedione (A). The same parameters were measured in simultaneously taken peripheral blood. mRNA concentrations of adrenal-specific enzymes CYP11B1 and CYP11B2 and ACTH and angiotensin II (AII) receptors were measured in tumor tissue. Main Outcome Measures:Adrenal-specific steroids/enzymes were assessed.Results: 21DF, 17OHP, and A levels were measurable in all spermatic vein samples. The ratio (mean Ϯ SD) between spermatic vein and simultaneously taken peripheral blood samples was 37.8 Ϯ 56.3 (21DF), 132.0 Ϯ 249 (17OHP), and 57.0 Ϯ 68.2 (A). CYP11B1, CYP11B2, and ACTH and AII receptor mRNAs were detected in all tumors with a strong correlation between ACTH receptor mRNA in tumors and 21DF (r ϭ 0.85; P ϭ 0.015), 17OHP (r ϭ 1; P ϭ 0.01) and A (r ϭ 0.89; P ϭ 0.007) concentrations in peripheral blood. Conclusion:Testicular adrenal rest tumors produce adrenal-specific steroids and express adrenal-specific enzymes and ACTH and AII receptors, confirming the strong resemblance with adrenal tissue. Because AII receptors are present in tumor tissue, it can be hypothesized that AII may be an additional factor responsible for testicular adrenal rest tumor growth.

Determining clinical and biological indicators for health outcomes in adult patients with childhood onset of congenital adrenal hyperplasia

“…Despite this bias, our cohort was large enough to give power to our results, especially in women. The reduced number of men was also observed in other cohorts (6,11,34,35). The other bias is the genetic heterogeneity of the population.…”

“…Another interesting finding is the demonstration that clinical form of CAH (CF vs NCF diagnosed in childhood) does not seem to be a determining factor of adverse outcomes if the patients have controlled disease. Overall, the present study and the CaHASE cohort study suggest that poor health outcomes in adults are closely related to their treatment rather than to the severity of the enzyme deficiency (34,35). The long-term impact of these complications on bone, cardiovascular events, and mortality should be analyzed in a longitudinal way in this population.…”

“…We also showed that total glucocorticoid dose of hydrocortisone and fludrocortisone were determinants of TARTs. It has been shown that TARTs express adrenal-specific enzymes and ACTH (34). This could be an expression of a more severe form of CAH or noncompliance (i.e., less compliant patients received higher doses of glucocorticoid but nonetheless retained poor disease control and developed TARTs), or it could suggest that the doses of glucocorticoid were adjusted according to the presence or absence of TARTs.…”

The prevalence of testicular adrenal rest tumors and associated factors in postpubertal patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency

“…In most cases, the activity of 21-hydroxylase depends on the type of mutation; very low enzyme activity is associated with a high prevalence of TARTs [14]. That is, when there is no 21-hydroxylase activity, ACTH level would be very high in the early embryonic period, and the chance of the hyperplastic adrenal tissue migrating along with the testis should increase [8,13]. In the same context, the size of a TART can differ according to the type of CAH [18].…”

An adrenal rest tumour in the perirenal region in a patient with congenital adrenal hyperplasia due to congenital 3β-hydroxysteroid dehydrogenase deficiency

“…The aberrant adrenocortical cells within the testes are stimulated by pro-opiomelanocortin (POMC) in periods of suboptimal hormonal control inducing hypertrophy and hyperplasia (9). This hypothesis is supported by the presence of POMC receptors on tumour tissue and by the fact that TART also occur in other conditions with elevated plasma POMC concentrations such as Nelson's syndrome and Addison's disease (10,11). Furthermore, the presence of angiotensin II (AII) receptors on TART is additional evidence that the tumours arise from adrenal-like cells (11).…”