胰岛素自身免疫综合征三例

自身免疫性低血糖症（AIH）是低血糖的一种少见原因,其临床特点为自发性低血糖发作、高胰岛素血症及胰岛素抗体或胰岛素受体抗体阳性.根据自身抗体的不同可以分为两种类型：（1）在无外源性胰岛素应用时出现针对内源性胰岛素的抗体（IAA）阳性,称为胰岛素自身免疫综合征（IAS）,1970年由日本Hirata等首次报道,又称Hirata病[1];（2）是针对靶细胞表面的胰岛素受体的抗体（IRA）阳性,称为B型胰岛素抵抗综合征（TBIRS）,较罕见[2],部分可出现低血糖.我院自2009年报道1例IAS后[3],陆续出现数例,现再报告3例IAS患者,以提高临床认识.     

1例胰岛素自身免疫综合征患者的动态血糖监测

胰岛素自身免疫综合征（IAS）又称自身免疫性低血糖（AIH）,是一种罕见类型的低血糖症,1970年由日本Hirata首次报道,故又称Hirata病。临床以反复发作的低血糖、高胰岛素血症及胰岛素自身抗体（IAA）或胰岛素受体抗体阳性为表现。AIH在日本被列为自发性低血糖症的第3大病因。国内只有少数病例报道,无相关流行病学资料。现将1例IAS患者动态血糖监测结果报道如下。     

他巴唑对甲亢患者血中胰岛素抗体的影响

胰岛素自身免疫综合征 (IAS)是由日本学者 Harita 1970年首次报道的。截至 1992年底日本统计的资料共 197例。在日本 IAS已成为引起低血糖的第三位原因 [1 ] 。美国、欧洲有少数病例报道。国内至 1998年底共 6例。IAS的临床特征为自发性低血糖而没有使用外源性胰岛素的证据 ,高水平具有免疫活性的胰岛素和存在高滴度的胰岛素自身抗体 (IAA) [2 ] 。 IAA的产生认为与患者使用含巯基 (- SH)的药物有关 ,尤其是他巴唑。在服用他巴唑的甲亢患者血中胰岛素抗体的发生率报道不一 ,Takei发现在 2 0 6例他巴唑治疗的甲亢患者血清中 IAA的检…     

胰岛素自身免疫综合征合并Graves病1例及文献分析

胰岛素自身免疫综合征(IAS)是指从未使用过胰岛素的患者发生的严重自发性低血糖,由遗传因素和环境因素共同作用,大部分患者携带DRB1* 0406基因,多合并Graves病等自身免疫性疾病,以服用甲巯咪唑等药物为诱因,以血浆高胰岛素水平、高C肽水平、高滴度的胰岛素自身抗体(IAA)为主要特征.IAS具有自限性,停用诱发药物,辅以低碳水化合物、高蛋白、高纤维饮食,必要时给予小剂量糖皮质激素及免疫抑制剂,多数可缓解.     

胰岛素自身免疫综合征三例并文献复习

胰岛素自身免疫综合征（insulin autoimmune syndrome，IAS）是引起低血糖的重要原因之一。自上个世纪70年代Hirata首先报道以来，近30余年来临床报道逐渐增多。正确认识IAS有助于低血糖的早期诊断和恰当处理。本研究在报道北京协和医院诊断的3例IAS的基础上，综合分析我国目前已经报道的37例IAS的临床资料，并与日本的IAS资料比较，提出中国人群IAS的临床特点，供临床参考。     

自身免疫性低血糖症

自身免疫性低血糖症（autoimmune hypoglycemia，AIH）又称胰岛素自身免疫综合征（insulin autoimmune syndrome，IAS），1970年由日本Hirata首次报道，故又称Hirata病。AIH在日本被列为自发性低血糖症的第三大病因，也是罕见病因。其临床特征为反复空腹或餐后晚期的低血糖发作，血胰岛素水平升高，胰岛素自身抗体（IAA）或胰岛素受体抗体阳性。     

硫普罗宁导致胰岛素自身免疫综合征四例

胰岛素自身免疫综合征（IAS）为血中非外源性胰岛素诱导的高浓度免疫活性胰岛素（IRI）和高效价胰岛素自身抗体（IAA）引起，以反复发作、严重自发性低血糖为特征的一种罕见疾病。以下报告4例硫普罗宁导致的IAS。[第一段]     

质子泵抑制剂致胰岛素自身免疫综合征一例

胰岛素自身免疫综合征(IAS)是一种少见的自身免疫性内分泌疾病,是由于自身免疫、自身抗体作用引起的一组低血糖综合征。本文报道1例与质子泵抑制剂使用有关的IAS,旨在提醒临床医生在应用该类药物时患者若出现低血糖,需考虑到IAS发生的可能,减少误诊率,使患者得到快速有效的治疗。     

α-硫辛酸引起的胰岛素自身免疫综合征研究进展

胰岛素自身免疫综合征（IAS）即自身免疫性低血糖症,又称为Hirata病。其主要特征是在没有使用外源性胰岛素的情况下,血液中却出现了高浓度的免疫活性胰岛素和高效价的胰岛素自身免疫抗体,引起自发性低血糖。     

中国人群胰岛素自身免疫综合征的临床特点分析

胰岛素自身免疫综合征(insulin autoimmune syndrome,IAS)又称自身免疫性低血糖症,由Hirata于1970年首先报道,是一种较为少见的内分泌疾病,临床上常存在误诊和漏诊.本研究汇总国内报道的56例IAS患者的临床资料,分析中国人群IAS的临床特点,供临床参考.     

Continuous glucose monitoring and Rituximab treatment in insulin autoimmune syndrome

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare cause of hypoglycemia. It is characterized by hyperinsulinemic hypoglycemia, elevated insulin autoantibody titers, no prior exposure to exogenous insulin and no pathological abnormalities of pancreatic islets. Hypoglycemia usually occurs in the post prandial and post absorptive state. Most cases of IAS are self-limiting, with resolution of symptoms within six months to one year. In intractable cases, treatment modalities include low-carbohydrate meals; acarbose; diazoxide; glucocorticoids; immune-suppressants like Azathioprine, cyclophosphamide, mycophenolate mofetil; plasmapheresis and partial pancreatectomy. Rituximab, an anti CD20 monoclonal antibody, was first used in 2016 in a patient with IAS who did not respond to glucocorticoids. Subsequently, there have been three more case reports of IAS where Rituximab was used along with other modalities of treatment. Here, we report the case of a 64-year old Asian Indian woman who presented with recurrent episodes of severe post prandial hypoglycemia and was diagnosed with insulin autoimmune syndrome. She was managed with continuous glucose monitoring and two doses of Rituximab 10 weeks apart, that resulted in resolution of hypoglycemia. This case report underlies the role of Rituximab as a first line agent for treatment of hypoglycemia in IAS.     

Recurrent hypoglycemia,a rare case of insulin autoimmune syndrome in a young African American male

Insulin autoimmune syndrome (IAS) is an uncommon cause of spontaneous hypoglycemia from hyperinsulinemia due to autoantibodies against endogenous insulin (Jian-Ping Chu, 2016). These individuals have no prior exposure to exogenous insulin. We report a case of a 35-year-old African American male, who presented to Vaughn Regional Medical Center in Selma, AL, after he was found to have seizures from hypoglycemia, with a blood sugar of 63 on presentation. He was never diagnosed with diabetes in the past, nor did he have a history of seizure disorder. He continued to be hypoglycemic during the initial period of his hospital stay. His fasting insulin level was 27 mIU/l (normal is less than 25, with presence of insulin autoantibodies (IAA), and a negative workup otherwise. This led us to include IAS as one of our differentials for his hypoglycemia.     

Insulin autoimmune syndrome is the third leading cause of spontaneous hypoglycemic attacks in Japan

From 1979 to 1981, questionnaires were sent to 2094 hospitals throughout Japan to investigate the causes of severe hypoglycemic attacks other than the administration of oral hypoglycemic agents or insulin preparations. The survey revealed three main causes for the attacks, of which the first was insulinoma, the second extrapancreatic neoplasms, and the third was insulin autoimmune syndrome (IAS), in descending order. Seven years later, a second survey was carried out, which showed the order of the three disorders as the cause of the hypoglycemic attacks to be the same as in the first survey. In both studies it was suggested that the IAS was frequently induced by thiol compounds.     

Drug-induced insulin autoimmune syndrome

Although insulin autoimmune syndrome (IAS) was found to be strongly related with methimazole, rapidly increasing numbers of cases with alpha lipoic acid-induced IAS have been confirmed to be reported since 2003. As alpha lipoic acid has gained popularity as a supplement for dieting and anti-aging, a warning should be issued.     

Insulin autoimmune syndrome: a rare cause of hypoglycaemia not to be overlooked

We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.     

Remission of insulin autoimmune syndrome in a patient with Grave's disease by treatment with methimazole.

The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacerbated IAS in the present case, although his HLA combination is identical to that of the previous cases.     

Insulin autoimmune syndrome: the second Dutch case

The insulin autoimmune syndrome (IAS) is the third leading cause of spontaneous hypoglycaemia in Japan. Here, we describe the second Dutch case. An 81-year-old man was analysed for collapse and attacks of disorientation, and was found to be hypoglycaemic during such an episode. The performed fasting test appeared to be positive. High levels of insulin and C-peptide postprandially and insulin antibodies were found. IAS was diagnosed.     

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

Insulin autoimmune syndrome (IAS) is an uncommon cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to endogenous insulin in individuals without previous exposure to exogenous insulin. IAS is the third leading cause of spontaneous hypoglycemia in Japan, and is increasingly being recognized worldwide in non-Asian populations. We report a case of IAS in a Caucasian woman with recurrent complaints of hypoglycemia, with laboratory findings of serum glucose 2.5 mmol/L (45 mg/dL), insulin 54,930 pmol/L (7,909 μIU/mL), connecting peptide (C-peptide) 4,104 pmol/L (12.4 ng/mL), and a corresponding insulin to C-peptide molar ratio of 13.4 during a spontaneous hypoglycemic event. Autoantibodies to insulin were markedly elevated at > 50 kU/L (> 50 U/mL). IAS should be considered in the differential diagnosis of hypoglycemia in non-diabetic individuals. Distinction from insulinoma is especially crucial to prevent unwarranted invasive procedures and surgical interventions in hypoglycemic patients.     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies

OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan and so far only 27 IAS cases have been described from outside Asia. We describe two unrelated Portuguese patients with IAS and characterise their insulin autoantibodies and HLA alleles. PATIENTS: Patient 1, a 24-year-old white female suffered an episode of unconsciousness in the late postprandial state and blood glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml (normal range 0-30 microIU/ml). She was receiving monthly injections of penicillin G for the prophylaxis of recurrent tonsillitis. Patient 2, was a 19-year-old white female, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-56 mg/dl. Very high insulin levels (602-708 microIU/ml) were present. METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi-quantitative method, were strongly positive in both patients (91.7% in patient 1 and 88.6% in patient 2; normal range < or =7%). Sephadex G-100 chromatography of the sera showed most of insulin immunoreactivity present in the void volume which was retained by an affinity column with anti-human-immunoglobulin G antibodies (87% and 95% from patients 1 and 2 respectively). Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibody and DRB1*0403 in patient 2. CONCLUSIONS: These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.