Enikeeva S R, Chugunov I S, Kareva M A, Kurkina M V, Zakharova E Y, Michailova S V, Bezlepkina O B, Peterkova V A, Mokrysheva N G
Endocrinology Research Centre.
Research Centre for Medical Genetics.
Probl Endokrinol (Mosk). 2023 Dec 5;70(3):83-92. doi: 10.14341/probl13335.
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.
To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.
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.
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.
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.
X连锁肾上腺脑白质营养不良（X-ALD）是一种严重的神经退行性代谢疾病，在新生男婴中的发病率为1:17,000。肾上腺功能不全（AI）是X-ALD的主要组成部分，发病率占患者的70-80%，若不及时治疗会危及生命。在整个疾病过程中都有可能发生AI，且没有任何预测AI出现的因素，这表明有必要对X-ALD患者的AI进行研究，以优化当前的诊断和治疗方案。
研究X-ALD所致原发性肾上腺功能不全的诊断和治疗特点。
对2014年至2022年期间在俄罗斯国立皮罗戈夫研究医科大学内分泌研究中心儿科内分泌科、医学遗传研究中心、儿科研究与临床研究所（俄罗斯儿童临床医院独立结构单元，位于俄罗斯莫斯科）接受检查和治疗的66例男性患者进行了一项回顾性观察比较研究。所有患者均被诊断为原发性AI且基因确诊为X-ALD。
X-ALD表现的中位年龄为6.6岁[4.7；11.1]。AI诊断的最早年龄在临床前期为1.5岁，出现临床症状时为1岁8个月。在AI表现时对22.7%（15/66例患者）进行了肾素水平研究，发现7例患者存在盐皮质激素缺乏。39.4%（n=66）的患者家族史呈阳性，仅15.1%（10/66例患者）的疾病在临床前期确诊。59.1%（n=66）确诊为疾病的脑型（cALD），16.6%为肾上腺脊髓神经病（AMN），24.2%为孤立性肾上腺功能不全（PAI）。AMN组患者AI确诊年龄（15.6岁）与cALD组患者（7.4岁，p=0.001）和PAI组患者（
