[Adrenal insufficiency as part of X-linked adrenoleukodystrophy].

Abstract

Background:  X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70-80% of patients, adrenal insufficiency (AI) is a life-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms.

Aim:  To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.

Materials and methods:  A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children's Clinical Hospital (Moscow, Russia) for 2014-2022. All of patients were diagnosed with primary AI and a genetically confirmed X-ALD.

Results:  The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years at the preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) the cerebral form of the disease (cALD) was established, in 16.6% - adrenomyeloneuropathy (AMN), and in 24.2% - isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11 and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI.

Conclusion:  It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed to prescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.