Is subclinical adrenal failure in adrenoleukodystrophy/adrenomyeloneuropathy reversible?
X-linked adrenoleukodystrophy/adrenomieloneuropathy (ALD/AMN) is a progressive neurodegenerative disorder due to mutations in the ABCD1 gene encoding the ABC transporter ALDP. Mutations in ALDP impair peroxisomal β-oxidation of very long chain fatty acids (VLCFA), resulting in elevated levels of VLCFA in plasma, nervous system, and adrenals. Lorenzo's oil, combined with VLCFA- poor diet, normalizes plasma VLCFA within 1 month, but it does not prevent the progression of pre-existing neurological symptoms. No previous study analyzed the effect of Lorenzo's oil therapy on adrenal function.To investigate short-term effects of Lorenzo's oil, combined with VLCFA- poor diet, on adrenal function of AMN patients with early subclinical signs of adrenal failure.Seven AMN subjects underwent VLCFA-restricted diet combined with Lorenzo's oil (45 ml/day po), without steroid therapy, for 6 months.All patients had elevated ACTH at baseline, and a significant reduction was evident after 6 months (median ACTH at baseline: 1300 pg/ml, range: 720- 2100; median ACTH at 6 months: 186 pg/ml, range: 109-320, p: 0.0156). Cortisol was normal both at baseline and after 6 months. VLCFA dropped in all patients during the 6- month follow-up, and no patient required glucocorticoid replacement therapy.Adrenal insufficiency in ALD/AMN is probably due to a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of the adrenal cell membrane functions. In an early phase, Lorenzo's oil therapy may be able to improve VLCFA clearance and restore a normal ACTH receptor activity, and hypoadrenalism may be potentially reversible.