Vol.:(0123456789) 1 3 Journal of Endocrinological Investigation https://doi.org/10.1007/s40618-020-01362-x REVIEW Bilateral testicular masses and adrenal insufciency: is congenital adrenal hyperplasia the only possible diagnosis? First two cases of TARTS described in Addison‑only X‑linked adrenoleukodystrophy and a brief review of literature A. S. Tresoldi 1,2  · N. Betella 1,2  · V. Hasenmajer 3  · C. Pozza 3  · W. Vena 1,2  · B. Fiamengo 4  · L. Negri 5  · M. Cappa 6  · A. G. A. Lania 1,7  · A. Lenzi 3  · A. M. Isidori 3  · A. Pizzocaro 1 Received: 11 May 2020 / Accepted: 12 July 2020 © Italian Society of Endocrinology (SIE) 2020 Abstract Background Testicular adrenal rest tumors (TARTs) are benign masses deemed to originate from pluripotent testicular steroidogenic cells that grow under chronic ACTH stimulation. These lesions, occasionally misdiagnosed as Leydig cell tumors (LCTs), are typically described in patients with congenital adrenal hyperplasia (CAH). X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of beta-oxidation with accumulation of very long chain fatty acids (VLCFAs) in various tissues, and a rare cause of primary adrenal insufciency (PAI). TARTs have never been associated with X-ALD. Case 1 description A 19-year old male, who had previously undergone bilateral enucleation of presumed LCTs, was referred to our unit. Follow-up scans showed persistent bilateral lesions compatible with TARTs. Biochemical exams revealed PAI but excluded CAH. A serum VLCFAs panel was consistent with X-ALD, with gene testing confrming the diagnosis. Histologi- cal revision of the previously resected testicular lesions was compatible with TARTs. Start of glucocorticoid replacement therapy was associated with a reduction of testicular masses. Case 2 description A 26-year old X-ALD male was diagnosed with bilateral testicular lesions compatible with TARTs. These lesions increased after ACTH elevation following switch to modifed-release hydrocortisone. Clinical and sonographic fnd- ings allowed for a “watchful-waiting" approach, avoiding unnecessary surgery. Conclusion These are the frst cases reported of TARTs in patients with X-ALD-associated PAI. Testicular lesions in patients with an early onset of ACTH elevation, regardless of the cause, should always be thoughtfully investigated, as they may reveal themselves as TARTs. We suggest that all patients afected from chronic ACTH elevation of a young age of onset should undergo testicular ultrasound in order to evaluate the presence of these lesions. GRT in these patients might also help preserving fertility. Keywords Adrenal rests · Adrenoleukodystrophy · Adrenal insufciency · Testicular mass * W. Vena walter.vena@humanitas.it 1 Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Center - IRCCS -, Via Manzoni, 56, 20089 Rozzano, MI, Italy 2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy 3 Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy 4 Pathology, Humanitas Clinical and Research Center - IRCCS -, Rozzano, MI, Italy 5 Division of Gynecology and Reproductive Medicine, Humanitas Fertility Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI, Italy 6 Endocrinology Unit, IRCCS “Bambino Gesù” Children’s Hospital, Rome, Italy 7 Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy