PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production.

Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned.

Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.

PMM2-CDG 是最常见的先天性糖基化 (CDG) 疾病，占已知影响 N-糖基化的 CDG 病例的近 65%。N-糖基化异常可能对许多内分泌轴产生负面影响。关于 N-糖基化受损对下丘脑-垂体-肾上腺轴功能的影响以及 CDG 患者是否有继发性肾上腺皮质功能不全和肾上腺皮质醇生成减少的风险，我们知之甚少。

皮质醇和促肾上腺皮质激素浓度在上午 7 点 44 分至下午 1 点之间同时测量了 43 名受试者（20 名女性，中位年龄 12.8 岁，范围 0.1 至 48.6 岁）参与正在进行的国际多中心自然史研究 PMM2- CDG（ClinicalTrials.gov 标识符：NCT03173300）。在 43 名受试者中，11 名（25.6%）的皮质醇低于 5 μg/dl，ACTH 水平低至正常，提示继发性肾上腺功能不全。11 名受试者中有 2 名已确认中枢肾上腺功能不全，并在患病期间接受氢化可的松替代治疗和/或应激给药；3 人对 ACTH 低剂量刺激试验的皮质醇反应正常，1 人皮质醇反应低于正常，但尚未开始治疗；其余 5 个计划即将进行刺激测试。

我们的研究结果表明，PMM2-CDG 患者可能存在肾上腺功能不全的风险。监测早晨皮质醇和 ACTH 水平应该是 PMM2-CDG 患者标准护理的一部分。