Kopczak Anna, Schumacher Adrian-Minh, Nischwitz Sandra, Kümpfel Tania, Stalla Günter K, Auer Matthias K
Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, MunichGermany.
Institute for Stroke and Dementia Research.
Endocrinol Diabetes Metab Case Rep. 2017 May 25;2017. doi: 10.1530/EDM-17-0010. eCollection 2017.
The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE) gene. Immune deficiency, hypoparathyroidism and Addison's disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD) antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS). The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3-4 times per day. GAD antibody-associated limbic encephalitis (LE) was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.
Episodic nausea cannot only be a sign of Addison's disease, but can also be caused by epileptic seizures with gastrointestinal aura due to limbic encephalitis.GAD antibodies are not only found in diabetes mellitus type 1, but they are also associated with autoimmune limbic encephalitis and can appear over time.Limbic encephalitis can be another manifestation of autoimmune disease in patients with APECED/APS-1 that presents over the time course of the disease.
自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）综合征是一种由自身免疫调节因子（AIRE）基因突变引起的遗传性疾病。免疫缺陷、甲状旁腺功能减退和自身免疫功能障碍导致的Addison病是APECED的主要临床症状。我们报告了一名21岁的APECED女性患者，其AIRE基因存在两个失活突变。她突然出现周期性恶心。通过促肾上腺皮质激素（ACTH）刺激试验诊断为肾上腺功能不全。尽管开始使用氢化可的松和氟氢可的松进行激素替代治疗，但恶心持续存在，患者出现认知缺陷和兴趣丧失，导致诊断为抑郁症。她被收治到精神科进行进一步的诊断评估。脑电图显示局灶性癫痫样放电。谷氨酸脱羧酶（GAD）抗体8年前为阴性，现在血清和脑脊液中升高。寡克隆带阳性，表明中枢神经系统（CNS）存在鞘内抗体产生的炎症过程。周期性恶心被确定为间脑性癫痫发作，临床上表现为胃肠道先兆，随后每天约发生3 - 4次意识减退发作。诊断为GAD抗体相关边缘叶脑炎（LE）。除抗癫痫治疗外，开始使用皮质类固醇进行免疫抑制治疗，随后使用硫唑嘌呤。自身免疫性疾病内分泌患者出现恶心和呕吐提示肾上腺功能不全。然而，我们的病例报告表明，发作性恶心可能是APECED患者中GAD抗体相关LE引起的癫痫发作的症状。
发作性恶心不仅可能是Addison病的体征，也可能由边缘叶脑炎伴胃肠道先兆的癫痫发作引起。GAD抗体不仅见于1型糖尿病，还与自身免疫性边缘叶脑炎相关，且可随时间出现。边缘叶脑炎可能是APECED/APS - 1患者自身免疫性疾病在疾病进程中出现的另一种表现形式。
