Endocrine Abstracts

Testicular adrenal rest tumors (TARTs) are benign masses causing testicular damage and infertility. Their development is attributed to chronic stimulation of elevated ACTH levels. Several diseases are characterized by an increase of ACTH, however TARTs have been described almost exclusively in patients with congenital adrenal hyperplasia (CAH), excluding only rare cases. X-linked adrenoleukodystrophy (X-ALD) is a rare cause of primary adrenal insufficiency (PAI). It is a genetic metabolic disorder of beta-oxidation with accumulation of very long chain fatty acids primarily in the adrenal cortex and central nervous system. In 2021, TARTs were reported for the first time in two patients with X-ALD associated PAI. In this article, we present two brothers with X-ALD-associated PAI. The youngest developed PAI first at the age of 10 after an adrenal crisis. Treatment with hydrocortisone was started with a median daily dose of 10 mg/m² body surface area. Following the patient’s diagnosis, the oldest brother was also found to have X-ALD: at that time, he was 14 year old and presented symptoms of attention deficit hyperactivity disorder, but no previous episodes of possible unrecognized adrenal crisis. In fact, biochemical exams revealed only a moderate increase of ACTH levels and low normal values of cortisol; however, glucocorticoid treatment was prudently started. The younger brother was deemed eligible for hematopoietic cell transplant to prevent progression of cerebral disease, which was already detectable in his older brother. During screening programs, a left testicular lesion of 7×7 mm was accidentally discovered and then enucleated, resulting compatible with a TART. Even his older brother underwent testicular ultrasound, which resulted normal. This is the third case of TARTs described in a patient with X-ALD-associated PAI. The genetic factors may play a minor role in the onset of TARTs, as reported in these siblings. The development of TARTs seems to be more related to the early onset of the disease and poor hormonal control. Indeed, only the youngest showed a prepubertal onset of PAI, probably unrecognized for several months before the correct diagnosis. Testicular lesions should be always investigated in patients with PAI, regardless of the cause, to avoid misdiagnosis and unnecessary testicular surgery. Considering these recent findings, the prevalence of TARTs is underestimated and should be considered not only in CAH patients, but at least in those patients with an early onset of chronic ACTH elevation, a poor hormonal control, or fertility problems.