Endocrinology and Metabolism

Case Reports

Obesity and Metabolism
Recurrent Insulin Autoimmune Syndrome Caused by α-Lipoic Acid in Type 2 Diabetes: Sang Mook Bae, Myoung Nam Bae, Eun Young Kim, Il Kyu Kim, Min Woo Seo, Jin Kyeong Shin, Sung Rae Cho, Gui Hwa Jeong; Endocrinol Metab. 2013;28(4):326-330. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.326

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Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed α-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

Citations

Citations to this article as recorded by

Long-term follow-up after discharge witnesses a slow decline of insulin autoantibodies in patients with insulin autoimmune syndrome complicated with Grave’s disease: a report of two cases
Lili Zhao, Jinzhi He, Shandong Ye, Chao Chen, Jie Zhu, Chunchun Xiao, Tingni Wu, Zhicheng Liu
BMC Endocrine Disorders.2023;[Epub] CrossRef
Postprandial hyperinsulinemic hypoglycemia
A. A. Akmedova, F. O. Ushanova
FOCUS. Endocrinology.2023; 4(3): 74. CrossRef
Effects of alpha lipoic acid on metabolic syndrome: A comprehensive review
Nahid Najafi, Soghra Mehri, Mahboobeh Ghasemzadeh Rahbardar, Hossein Hosseinzadeh
Phytotherapy Research.2022; 36(6): 2300. CrossRef
Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features
Umberto Capece, Simona Moffa, Ilaria Improta, Gianfranco Di Giuseppe, Enrico Celestino Nista, Chiara M. A. Cefalo, Francesca Cinti, Alfredo Pontecorvi, Antonio Gasbarrini, Andrea Giaccari, Teresa Mezza
Nutrients.2022; 15(1): 18. CrossRef
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by alpha‐lipoic acid
Zuojun Li, Yanhong Su, Dan Yi, Cuifang Wu, Weijin Fang, Chunjiang Wang
Journal of Clinical Pharmacy and Therapeutics.2021; 46(5): 1295. CrossRef
Scientific opinion on the relationship between intake of alpha‐lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome
Dominique Turck, Jacqueline Castenmiller, Stefaan de Henauw, Karen Ildico Hirsch‐Ernst, John Kearney, Helle Katrine Knutsen, Inge Mangelsdorf, Harry J McArdle, Androniki Naska, Carmen Pelaez, Kristina Pentieva, Alfonso Siani, Frank Thies, Sophia Tsabouri,
EFSA Journal.2021;[Epub] CrossRef
Management of Insulin Autoimmune Hypoglycaemia: Single‐centre experience from Western India with systematic review of world literature
Muniraj Patel, Ravikumar Shah, Swati Ramteke‐Jadhav, Virendra Patil, Shivendra Kumar Patel, Anurag Lila, Nalini Shah, Tushar Bandgar
Clinical Endocrinology.2020; 92(5): 409. CrossRef
Glucose Changes in a Patient With Insulin Autoimmune Syndrome Demonstrated by Continuous Glucose Monitoring
Shi-Dou Lin, Shang-Ren Hsu
AACE Clinical Case Reports.2019; 5(1): e35. CrossRef
Insulin Autoimmune Syndrome in a 25-Year-Old, Previously Healthy Kuwaiti Man
Einas Alrashidi, Thamer Alessa
Case Reports in Endocrinology.2019; 2019: 1. CrossRef
Insulin autoimmune syndrome in an Argentine woman taking α-lipoic acid: A case report and review of the literature
Valentina Izzo, Carla Greco, Diana Corradini, Marco Infante, Maria Teresa Staltari, Maria Romano, Alfonso Bellia, Davide Lauro, Luigi Uccioli
SAGE Open Medical Case Reports.2018; 6: 2050313X1881960. CrossRef
Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome
David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer,
The Journal of Clinical Endocrinology & Metabolism.2018; 103(10): 3845. CrossRef
Current Status of Health Foods Including Their Interactions with Drugs and Adverse Events
Yoshiro Saito
YAKUGAKU ZASSHI.2018; 138(12): 1511. CrossRef
Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients
A Veltroni, G Zambon, S Cingarlini, M V Davì
Endocrinology, Diabetes & Metabolism Case Reports.2018;[Epub] CrossRef
GLP‑1R agonists ameliorate peripheral nerve dysfunction and inflammation via p38 MAPK/NF‑κB signaling pathways in streptozotocin‑induced diabetic rats
Jingjing Ma, Min Shi, Xiangcheng Zhang, Xiaoning Liu, Juan Chen, Ridong Zhang, Xingzhou Wang, Hong Zhang
International Journal of Molecular Medicine.2018;[Epub] CrossRef
Insulin autoimmune syndrome associated with alpha-lipoic acid in a young woman with no concomitant disease
Sang Bae Lee, Min Young Lee, Ji Hong You, Seong Han Kim, Ji Sun Nam
Yeungnam University Journal of Medicine.2017; 34(1): 115. CrossRef
The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
Adel A.A. Ismail
Clinical Chemistry and Laboratory Medicine (CCLM).2016; 54(11): 1715. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
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Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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Abstract PDF PubReader

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

Citations

Citations to this article as recorded by

Insulin Autoimmune Syndrome: A Systematic Review
MingXu Lin, YuHua Chen, Jie Ning, Tatsuya Kin
International Journal of Endocrinology.2023; 2023: 1. CrossRef
Safety of Antithyroid Drugs in Avoiding Hyperglycemia or Hypoglycemia in Patients With Graves’ Disease and Type 2 Diabetes Mellitus: A Literature Review
Yu-Shan Hsieh
Cureus.2023;[Epub] CrossRef
Case report: hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in young Taiwanese woman with Graves’ disease
Hsuan-Yu Wu, I-Hua Chen, Mei-Yueh Lee
Medicine.2022; 101(25): e29337. CrossRef
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole
Linli Sun, Weijin Fang, Dan Yi, Wei Sun, Chunjiang Wang
Journal of Clinical Pharmacy and Therapeutics.2021; 46(2): 470. CrossRef
Preoperative plasmapheresis experience in Graves’ disease patients with anti-thyroid drug-induced hepatotoxicity
Tugce Apaydın, Onur Elbasan, Dilek Gogas Yavuz
Transfusion and Apheresis Science.2020; 59(5): 102826. CrossRef
Glycemic variation in uncontrolled Graves’ disease patients with normal glucose metabolism: Assessment by continuous glucose monitoring
Gu Gao, Feng-fei Li, Yun Hu, Reng-na Yan, Bing-li Liu, Xiao-mei Liu, Xiao-fei Su, Jian-hua Ma, Gang Hu
Endocrine.2019; 64(2): 265. CrossRef
Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series
Yimin Shen, Xiaoxiao Song, Yuezhong Ren
BMC Endocrine Disorders.2019;[Epub] CrossRef
Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome
David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer,
The Journal of Clinical Endocrinology & Metabolism.2018; 103(10): 3845. CrossRef
MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia
Nana Esi Kittah, Adrian Vella
European Journal of Endocrinology.2017; 177(1): R37. CrossRef
Insulin autoimmune syndrome during the administration of clopidogrel
Eijiro Yamada, Shuichi Okada, Tsugumichi Saito, Aya Osaki, Atushi Ozawa, Masanobu Yamada
Journal of Diabetes.2016; 8(4): 588. CrossRef
Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog
Chih-Ting Su, Yi-Chun Lin
Endocrinology, Diabetes & Metabolism Case Reports.2016;[Epub] CrossRef
Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome
Jung Suk Han, Han Ju Moon, Jin Seo Kim, Hong Il Kim, Cheol Hyeon Kim, Min Joo Kim
The Ewha Medical Journal.2016; 39(4): 122. CrossRef
2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis
Douglas S. Ross, Henry B. Burch, David S. Cooper, M. Carol Greenlee, Peter Laurberg, Ana Luiza Maia, Scott A. Rivkees, Mary Samuels, Julie Ann Sosa, Marius N. Stan, Martin A. Walter
Thyroid.2016; 26(10): 1343. CrossRef
Insulin Autoimmune Syndrome in a Patient with Hashimoto's Thyroiditis
In Wook Song, Eugene Han, Nan Hee Cho, Ho Chan Cho
Journal of Korean Thyroid Association.2014; 7(2): 180. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

A Case of Insulin Autoimmune Syndrome in a Patient with Partial Hypopituitarism.: Obin Kwon, Eun Young Park, Jin Young Yoon, Kwang Joon Kim, Yong ho Lee, Jae Won Hong, Eun Jig Lee, Sung Kil Lim, Hyun Chul Lee, Bong Soo Cha; J Korean Endocr Soc. 2009;24(4):281-286. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.281

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23 Download

Abstract PDF: Insulin autoimmune syndrome is one of the rare causes of hypoglycemia, and characterized by hyperinsulinemic hypoglycemia associated with high titer of antibodies to endogenous insulin. We report a case of insulin autoimmune syndrome in a 57-year-old woman, presenting with mental changes due to hypoglycemia. She had no history of diabetes or insulin administration. The serum C-peptide level was 4.69 ng/mL and the insulin concentration was 229.55 microU/mL, when fasting plasma glucose level was 32 mg/dL. The insulin-to-glucose ratio was 7.17, while there was no radiologic evidence of insulinoma. The insulin antibody level was over 100 microU/mL, resulting in the diagnosis of insulin autoimmune syndrome. Hormonal studies revealed partial hypopituitarism and a lack of glucagon-response to hypoglycemia. Hypoglycemia disappeared with replacement of prednisolone with levothyroxine therapy. Under secretion of growth hormone and of adrenocorticotropic hormone due to hypopituitarism were associated with insufficient counterregulation to hypoglycemia. One should keep in mind that insulin autoimmune syndrome or hypopituitarism is one cause of hypoglycemia in patients with no history of diabetes, and corticosteroid can be an effective treatment for both diseases.

Ensulin Autoimmune Syndrome in a Patient with Methimazole-Treated Graves' Disease: A Case report.: Joong Kyu Lim, Yong An Woo, Sung Jin Kang, Sung Sik Yoo, Kun Young Hong, Soon Ho Kim; J Korean Endocr Soc. 1998;13(4):612-616. Published online January 1, 2001

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Abstract PDF: Insulin autoimmune syndrome (IAS) includes fasting or reactive hypoglycemia, hyperinsulinemia and the presence of insulin-binding antibodies in patients who have never been exposed to exogenous insulin. This report concems a 29-year-old male patient with Graves disease who had history of having taken methimazole for two months, without any consequence, 6 months previously. However, when methimazole was administered again for three weeks, the patient suffered hypoglycemia during the next fourth week. He denied history of diabetes mellitus (DM), of taking any oral hypoglycemic agent or of having received insulin injection. Laboratory data showed total serum insulin level > 300 pu/mL, C-peptide reactivity (CPR) 8.0ng/mL and insulin antibody 89%. After stopping methimazole, he was treated with radioiodine (131I). There was no episode of hypoglycemic attack during 8 months of follow-up.

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