PDF(Pubmed)
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.
OBJECTIVE: To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.
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.
CONCLUSIONS: 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.
OBJECTIVE: To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.
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.
CONCLUSIONS: 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.
摘要：
背景：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，在新生男孩中频率为1：17,000。作为X-ALD的主要部分，发病率为70-80％的患者，肾上腺功能不全（AI）是一种威胁生命的疾病，没有及时治疗。在整个疾病持续时间内发展AI的可能性以及缺乏任何AI加入的预测因素表明，有必要在X-ALD患者中研究AI以优化当前的诊断和治疗算法。
目的：研究X-ALD所致原发性肾上腺功能不全的诊断和治疗特点。
方法：对66例男性患者进行了回顾性观察性比较研究，在内分泌研究中心儿科内分泌科检查和治疗，医学遗传学研究中心,皮罗戈夫俄罗斯国立研究医科大学儿科研究与临床研究所独立结构单位俄罗斯儿童临床医院（莫斯科，俄罗斯）2014-2022年。所有患者均被诊断为原发性AI和遗传证实的X-ALD。
结果：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阶段为1.5岁，有临床症状的年龄为1年8个月。肾素水平在表现为AI的22.7%（15/66例），7例患者发现盐皮质激素缺乏。39.4%的患者家族史为阳性（n=66），只有15.1%(10/66例)的患者在临床前阶段确诊.在59.1%(n=66)中，建立了疾病的大脑形式(cALD)，在16.6%-肾上腺神经病变（AMN），和24.2％-孤立的肾上腺功能不全（PAI）。AMN患者组的AI建立年龄（15.6岁）与cALD患者的AI建立年龄（7.4岁，p=0.001)和PAI(5.6年，p=0.000）。在cALD患者中，盐皮质激素治疗与糖皮质激素治疗同时进行，在AMN和PAI患者中，它在11个月和7个月后添加，分别（AMN和PAI组之间的差异无统计学意义）。激素联合治疗接受41%的cALD患者，54.5%的AMN患者和60%的PAI患者。
结论：有必要检查所有男性AI患者，无论表现年龄如何，以排除肾上腺脑白质营养不良，无论X-ALD表现年龄如何，检查患者是否存在AI也很重要。还需要评估AI表现中的肾素水平以及时开出盐皮质激素治疗。研究家族史是临床前阶段检测X-ALD的主要方法。
目的：研究X-ALD所致原发性肾上腺功能不全的诊断和治疗特点。
方法：对66例男性患者进行了回顾性观察性比较研究，在内分泌研究中心儿科内分泌科检查和治疗，医学遗传学研究中心,皮罗戈夫俄罗斯国立研究医科大学儿科研究与临床研究所独立结构单位俄罗斯儿童临床医院（莫斯科，俄罗斯）2014-2022年。所有患者均被诊断为原发性AI和遗传证实的X-ALD。
结果：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阶段为1.5岁，有临床症状的年龄为1年8个月。肾素水平在表现为AI的22.7%（15/66例），7例患者发现盐皮质激素缺乏。39.4%的患者家族史为阳性（n=66），只有15.1%(10/66例)的患者在临床前阶段确诊.在59.1%(n=66)中，建立了疾病的大脑形式(cALD)，在16.6%-肾上腺神经病变（AMN），和24.2％-孤立的肾上腺功能不全（PAI）。AMN患者组的AI建立年龄（15.6岁）与cALD患者的AI建立年龄（7.4岁，p=0.001)和PAI(5.6年，p=0.000）。在cALD患者中，盐皮质激素治疗与糖皮质激素治疗同时进行，在AMN和PAI患者中，它在11个月和7个月后添加，分别（AMN和PAI组之间的差异无统计学意义）。激素联合治疗接受41%的cALD患者，54.5%的AMN患者和60%的PAI患者。
结论：有必要检查所有男性AI患者，无论表现年龄如何，以排除肾上腺脑白质营养不良，无论X-ALD表现年龄如何，检查患者是否存在AI也很重要。还需要评估AI表现中的肾素水平以及时开出盐皮质激素治疗。研究家族史是临床前阶段检测X-ALD的主要方法。
