A S Tresoldi1,2, N Betella1,2, V Hasenmajer3, C Pozza3, W Vena4,5, B Fiamengo6, L Negri7, M Cappa8, A G A Lania1,9, A Lenzi3, A M Isidori3, A Pizzocaro1. 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. Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Center - IRCCS -, Via Manzoni, 56, 20089, Rozzano, MI, Italy. walter.vena@humanitas.it. 5. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. walter.vena@humanitas.it. 6. Pathology, Humanitas Clinical and Research Center - IRCCS -, Rozzano, MI, Italy. 7. Division of Gynecology and Reproductive Medicine, Humanitas Fertility Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI, Italy. 8. Endocrinology Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy. 9. Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy.
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 insufficiency (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 confirming the diagnosis. Histological 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 modified-release hydrocortisone. Clinical and sonographic findings allowed for a "watchful-waiting" approach, avoiding unnecessary surgery. CONCLUSION: These are the first 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 affected 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.
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 insufficiency (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 confirming the diagnosis. Histological 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 modified-release hydrocortisone. Clinical and sonographic findings allowed for a "watchful-waiting" approach, avoiding unnecessary surgery. CONCLUSION: These are the first 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 affected 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.
Entities:
Keywords:
Adrenal insufficiency; Adrenal rests; Adrenoleukodystrophy; Testicular mass
Authors: Manon Engels; Paul N Span; Antonius E van Herwaarden; Fred C G J Sweep; Nike M M L Stikkelbroeck; Hedi L Claahsen-van der Grinten Journal: Endocr Rev Date: 2019-08-01 Impact factor: 19.871
Authors: N M Stikkelbroeck; B J Otten; A Pasic; G J Jager; C G Sweep; K Noordam; A R Hermus Journal: J Clin Endocrinol Metab Date: 2001-12 Impact factor: 5.958
Authors: Troy Puar; Manon Engels; Antonius E van Herwaarden; Fred C G J Sweep; Christina Hulsbergen-van de Kaa; Karin Kamphuis-van Ulzen; Vasileios Chortis; Wiebke Arlt; Nike Stikkelbroeck; Hedi L Claahsen-van der Grinten; Ad R M M Hermus Journal: J Clin Endocrinol Metab Date: 2017-02-01 Impact factor: 5.958
Authors: M Fabrazzo; G Accardo; I Abbondandolo; G Goglia; D Esposito; G Sampogna; F Catapano; D Giugliano; D Pasquali Journal: J Endocrinol Invest Date: 2020-08-31 Impact factor: 4.256