Endocrine Abstracts

Testicular adrenal rest tumours (TARTs) are benign tumours deemed to originate from ectopic adrenal cells that descend with the testes during fetal development. These cells grow under chronic ACTH stimulation, typically in patients with congenital adrenal hyperplasia (CAH). TARTs have also been rarely described in other conditions characterised by chronically elevated ACTH, such as autoimmune primary adrenal insufficiency (PAI). These are benign lesions, but could be misdiagnosed as Leydig cell tumours (LCT). X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder of beta-oxidation that results in accumulation of very long chain fatty acids (VLCFA) in various tissues. The phenotypic spectrum is heterogeneous, with different age of onset and severity of neurological involvement. More than 50% of patients have PAI, but only 10% have ALD-associated PAI without neurological involvement, this usually presenting before the age of 10. A 19-year-old young male was referred to our Unit for assessment of elevated ACTH. He had previously undergone bilateral enucleation of presumed LCTs at the age of 8, and follow-up scans later showed persistent bilateral lesions compatible with TARTs, stable through the years. His past medical history was otherwise unremarkable, and clinical examination was normal. We also performed a semen analysis, which showed astheno-teratospermia. In order to exclude CAH, an androgen profile was requested, which showed a slightly elevated 17OHP (2.8 ng/ml) and normal androstenedione, DHEA-s and testosterone. An ACTH stimulation test was performed, which showed insufficient response of cortisol (6.7 μg/ml at 30′), but also a flat response of 17OHP to stimulus (2.8 ng/ml at 60′), confirming the diagnosis of PAI but ruling out CAH. Aldosterone and renin were normal, indicating a preserved mineralocorticoid production. Adrenal antibodies were negative. A serum VLCFA panel was consistent with X-ALD, with subsequent gene testing confirming the diagnosis (mutation c.346G>A of ABCD1 gene). A brain MRI was normal, supporting the diagnosis of Addison-only ALD.

Conclusion: Adrenoleukodystrophy should always be considered in any case of primary adrenal insufficiency diagnosed in young males, even when the clinical picture could suggest a different aetiology. We expect to confirm that the testicular lesions are indeed TARTs (a follow-up ultrasound is due to be performed, and histological revision of the previously resected testicular lesions is awaited) - this would be the first case ever reported of TARTs in a patient with ALD-associated PAI. This could warrant additional investigation for a potentially reversible cause of infertility in these patients.