AURENOLEUKUDYSTROPHY MAY RESEMBLE FAMILIAL ACTH UNRESPONSIVENESS

Abstract

Adrenoleukodystrophy (ALD) is a well-described cause of familial primary adrenal insufficiency in which neurological symptoms may be absent for many years. While the spectrum of adrenal insufficiency in ALD is variable, primary impairment of glucocorticoid secretion may resemble familial ACTH unresponsiveness, a different rare form of adrenal insufficiency. To distinguish ALD from other forms of familial adrenal insufficiency, we carried out the following studies in 3 male patients (age 11-16 yr): measurement of plasma saturated very-long-chain fatty acids (C26 and C26/C22 ratio), adrenal antibodies (AAb), plasma renin activity (PRA), and computerized tomography (CT) or magnetic resonance (MR) studies of the CNS. C26 was elevated above control in all three patients, 2.14 ± 1.21 μg/ml, mean ± S.D. (normal 0.33 ± 0.18) as was the C26/C22 ratio, 0.04 ± 0.01 (normal 0.01 ± 0.01), consistent with the diagnosis of ALD. AAb were undetectable in all patients. PRA was normal in one patient and elevated in two. Neurological examinations were unremarkable in all patients, without evidence of leukodystrophy on CT or MR scans. This study illustrates the need to consider ALD in the differential diagnosis of childhood familial primary adrenal insufficiency in the absence of neurological symptoms. Furthermore, it is important to recognize that ALD may present with isolated glucorticoid deficiency and thus may mimic ACTH unresponsiveness, which has separate genetic, prognostic, and therapeutic considerations.