Production of 11-oxygenated androgens by testicular adrenal rest tumors.

Abstract

CONTEXT\nTesticular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done.\n\n\nOBJECTIVE\nDefine the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART.\n\n\nPARTICIPANTS AND METHODS\nSteroids were measured in left (n=7) and right (n=4) spermatic vein- and simultaneously taken peripheral blood (n=7) samples from seven men with 21OHD and TART using liquid chromatography-tandem mass spectrometry. For comparison, we also measured the peripheral steroid concentrations in five adrenalectomized patients and twelve age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation.\n\n\nRESULTS\nCompared to peripheral blood of 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11β-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11β-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone, and lower levels of A4 and 11OHA4 after ACTH stimulation compared to adrenal cells, indicating ACTH-induced production of testosterone in TART.\n\n\nCONCLUSION\nIn patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic- versus peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.