Background: Testicular Adrenal Rest Tumors (TART) are a common complication in male patients with Congenital Adrenal Hyperplasia (CAH). TART are considered to have steroid-producing properties and may contribute to the androgen excess in CAH patients. This study aims to define the production of 11-oxygenated 19-Carbon (11oxC19) and sulfated steroids by TART.

Methods: Steroids were measured in previously collected left and right spermatic vein- and simultaneously taken peripheral plasma samples from seven male CAH patients using Liquid chromatography-mass spectrometry. In addition, the peripheral plasma steroid levels of CAH patients were compared with plasma samples of age- and BMI-matched controls and adrenalectomized controls.

Results:  Whereas 11-hydroxyandrostenedione (11OHA4) is reported to be the most highly elevated 11oxC19 steroid in adrenal vein samples, 11-hydroxytestosterone (11OHT) was most highly elevated in spermatic vein samples (84-fold) compared to peripheral blood, followed by 11-ketotestosterone (11-KT; 35-fold) and 11OHA4 (12-fold). 11-ketoandrostenedione (11KA4) was not elevated in spermatic vein blood. 11OHA4 was the most abundant 11oxC19 steroid in spermatic vein blood and correlated with TART weight (R=0.68), making it an interesting marker for TART progression. In addition, 16-hydroxyprogesterone (144-fold), 17-hydroxyprogesterone (105-fold), testosterone (70-fold), progesterone (43-fold), 21-deoxycortisol (22-fold), androstenedione (22-fold), and 17-hydroxyprogesterone sulfate (6-fold) were significantly elevated.

Conclusion: TART contributes to elevated levels of 11oxC19 steroids and exhibits an adrenocortical steroidogenic profile. However, the relatively high ratio of 11OHT in spermatic vein- versus peripheral vein blood likely stresses the metabolism of testosterone in TART that is -based on suppressed gonadotropin levels in some patients- suggested to be at least partially produced by TART itself and might also be percolated from surrounding gonadal tissue.