Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease
Open accessAbstract
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.
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Rare cases of insulin autoimmune syndrome with symptomatic hypoglycemia have been reported in patients treated with MMI.
“Rare cases of insulin autoimmune syndrome with symptomatic hypoglycemia have been reported in patients treated with MMI (146,147).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [147]
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Cites
Insulin Autoimmune Syndrome (Hirata Disease): Clinical Features and Epidemiology in Japan
Uchigata, Y., Eguchi, Y., Takayama-Hasumi, S., & Omori, Y. (1994) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(94)90040-x · Cited by 127 · see citing works
Strong association of insulin autoimmune syndrome with HLA-DR4
Uchigata, Y., Eguchi, Y., Takayama-Hasumi, S., Omon, Y., Hirata, Y., Kuwata, S., Tokunaga, K., Miyamoto, M., & Juji, T. (1992) · The Lancet · doi:10.1016/0140-6736(92)90080-m · Cited by 126 · see citing works
Uchigata, Y., Hirata, Y., Omori, Y., Iwamoto, Y., & Tokunaga, K. (2000) · Human Immunology · doi:10.1016/s0198-8859(99)00144-5 · Cited by 99 · see citing works
Spontaneous Hypoglycemia with Insulin Autoimmunity in Graves' Disease
Hirata, Y., TOMINAGA, M., ITO, J.-I., & Noguchi, A. (1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-81-2-214 · Cited by 97 · see citing works
Rituximab Selectively Suppresses Specific Islet Antibodies
Yu, L., Herold, K. C., Krause-Steinrauf, H. J., McGee, P. L., Bundy, B. N., Pugliese, A., Krischer, J., Eisenbarth, G. S., & for the Type 1 Diabetes TrialNet Anti-CD20 Study Group (2011) · Diabetes · doi:10.2337/db11-0674 · Cited by 85 · see citing works
METHIMAZOLE AND INSULIN AUTOIMMUNE SYNDROME WITH HYPOGLYCAEMIA
Hirata, Y. (1983) · The Lancet · doi:10.1016/s0140-6736(83)91031-0 · Cited by 83 · see citing works
Mechanism of Hypoglycemia Observed in a Patient with Insulin Autoimmune Syndrome
Ichihara, K., Shima, K., Saito, Y. M., Nonaka, K., Tarui, S., & Nishikawa, M. (1977) · Diabetes · doi:10.2337/diab.26.5.500 · Cited by 73 · see citing works
Uchigata, Y., Kuwata, S., Tsushima, T., Tokunaga, K., Miyamoto, M., Tsuchikawa, K., Hirata, Y., Juji, T., & Omori, Y. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.1.8325948 · Cited by 67 · see citing works
Insulin Autoimmune Syndrome PossiblyCaused by Alpha Lipoic Acid
Takeuchi, Y., Miyamoto, T., Kakizawa, T., Shigematsu, S., & Hashizume, K. (2007) · Internal Medicine · doi:10.2169/internalmedicine.46.1893 · Cited by 55 · see citing works
Ito, Y., Nieda, M., Uchigata, Y., Nishimura, M., Tokunaga, K., Kuwata, S., Obata, F., Tadokoro, K., Hirata, Y., Omori, Y., et al. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.10.5770 · Cited by 45 · see citing works
Association of HLA-DR and -DQ Genes with Graves Disease in Koreans
Park, M. H., Park, Y. J., Song, E. Y., Park, H., Kim, T. Y., Park, D. J., Park, K. S., & Cho, B. Y. (2005) · Human Immunology · doi:10.1016/j.humimm.2005.03.001 · Cited by 44 · see citing works
Self-citationEguchi, Y., Uchigata, Y., Yao, K., Yokoyama, H., Hirata, Y., & Omori, Y. (1994) · Autoimmunity · doi:10.3109/08916939409071354 · Cited by 37 · see citing works
Severe Autoimmune Hypoglycemia With Insulin Antibodies Necessitating Plasmapheresis
Yaturu, S., DePrisco, C., & Lurie, A. A. (2004) · Endocrine Practice · doi:10.4158/ep.10.1.49 · Cited by 36 · see citing works
Immunoendocrinology: Scientific and Clinical Aspects
Eisenbarth, G. S. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-478-4 · Cited by 26 · see citing works
Mechanism of hypoglycemia observed in a patient with insulin autoimmune syndrome
Ichihara, K., Shima, K., Saito, Y., et al. (1977) · Diabetes · doi:10.2337/diabetes.26.5.500 · Cited by 23 · see citing works
Spontaneous hypoglycemia and insulin autoantibodies in a patient with Graves' disease
Cho, B.-Y., Lee, H. K., Koh, C., & Min, H. K. (1987) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(87)80017-7 · Cited by 20 · see citing works
Roh, E. Y., Kim, H., Kim, S.-M., Lim, Y.-M., Han, B.-Y., & Park, M.-H. (2003) · The Korean Journal of Laboratory Medicine · Cited by 19 · see citing works
Self-citationA case report of insulin autoimmune syndrome in graves' disease.
Lee, K. S., Kim, J. H., Choi, W. H., Kim, T. W., & Kim, M. H. (2001) · Journal of Korean Endocrine Society · Cited by 5 · see citing works
Ensulin Autoimmune Syndrome in a Patient with Methimazole-Treated Graves' Disease: A Case report.
Lim, J. K., Woo, Y. A., Kang, S. J., Yoo, S. S., Hong, K. Y., & Kim, S. H. (2001) · Journal of Korean Endocrine Society · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“Rare cases of insulin autoimmune syndrome with symptomatic hypoglycemia have been reported in patients treated with MMI (146,147).”
BackgroundInsulin autoimmune syndrome: from diagnosis to clinical management
Censi, S., Mian, C., & Betterle, C. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.07.32 · Cited by 152 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia
Kittah, N. E., & Vella, A. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-1062 · Cited by 107 · see citing works
Church, D., Cardoso, L., Kay, R. G., Williams, C. L., Freudenthal, B., Clarke, C., Harris, J. R., Moorthy, M., Karra, E., Gribble, F. M., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00972 · Cited by 45 · see citing works
Insulin Autoimmune Syndrome: A Systematic Review
Lin, M., Chen, Y., & Ning, J. (2023) · International Journal of Endocrinology · doi:10.1155/2023/1225676 · Cited by 36 · see citing works
Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog
Su, C.-T., & Lin, Y. (2016) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-16-0079 · Cited by 23 · see citing works
Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series
Shen, Y.-M., Song, X., & Ren, Y. (2019) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0482-0 · Cited by 25 · see citing works
Insulin autoimmune syndrome during the administration of clopidogrel
Yamada, E., Okada, S., Saito, T., Osaki, A., Ozawa, A., & Yamada, M. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12385 · Cited by 14 · see citing works
HLA Alleles Associate with Insulin Autoimmune Syndrome
Yao, D., Jiang, J.-F., Zhou, Q., Feng, C., Chu, J.-P., Chen, Z., Yang, J., Xia, J., & Chen, Y. (2024) · Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy · doi:10.2147/dmso.s456466 · Cited by 10 · see citing works
Apaydın, T., Elbasan, O., & Yavuz, D. G. (2020) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2020.102826 · Cited by 12 · see citing works
Gao, G., Li, F.-F., Hu, Y., Yan, R., Liu, B.-L., Liu, X., Su, X., Ma, J., & Hu, G. (2018) · Endocrine · doi:10.1007/s12020-018-1820-0 · Cited by 11 · see citing works
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole
Sun, L., Fang, W.-J., Yi, D., Sun, W., & Wang, C.-J. (2020) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.13307 · Cited by 9 · see citing works
Wu, H.-Y., Chen, I.-H., & Lee, M. (2022) · Medicine · doi:10.1097/md.0000000000029337 · Cited by 9 · see citing works
Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome
Jung, S.-H., Moon, H.-J., Kim, J. S., Kim, H., Kim, C., & Kim, M. J. (2016) · Ewha Medical Journal · doi:10.12771/emj.2016.39.4.122 · Cited by 7 · see citing works
Self-citationMete, T., & Cesur, M. (2023) · Intercontinental Journal of Internal Medicine · doi:10.51271/icjim-0021 · Cited by 7 · see citing works
Unmasking Hirata: a mysterious case of Hypoglycemia triggered by immunologic storm
AbuBaha, M., Salameh, H., Abubaha, B., Dahabreh, Y., Marouf, O., Atary, M., Qubaja, H., Mansor, A., & Taha, H. (2026) · Oxford Medical Case Reports · doi:10.1093/omcr/omaf289 · Cited by 2 · see citing works
Insulin autoimmune syndrome in a patient with vitiligo: a case report and review of literature
Heydari, I., Maghsoomi, Z., Hatami, N., & Soltani, P. (2025) · Journal of Medical Case Reports · doi:10.1186/s13256-025-05219-w · Cited by 2 · see citing works
Insulin Autoimmune Syndrome in a Patient with Hashimoto's Thyroiditis
Song, I., Han, E., Nan, H.-C., & Ho, C.-C. (2014) · Journal of Korean Thyroid Association · doi:10.11106/cet.2014.7.2.180 · Cited by 1 · see citing works
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Lee, W. (2014) · Endocrinology and Metabolism · doi:10.3803/enm.2014.29.3.251
A Case of Methimazole-Induced Insulin Autoimmune Syndrome and Literature Review
王, 东. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.14102615
Kim, S. H., Baek, C., Song, S. K., & Kim, J. H. (2024) · International Journal of Thyroidology · doi:10.11106/ijt.2024.17.2.295
Self-citationOhnishi, M., Anno, T., Takahashi, K., Okauchi, S., Murakami, K., Kaku, K., Kaneto, H., & Kamei, S. (2025) · Internal Medicine · doi:10.2169/internalmedicine.5567-25
A case report and literature review of proton pump inhibitors inducing insulin autoimmune syndrome
Zhang, W., Wen, J., Qi, S., Zhang, G., Yang, X.-B., Zeng, L.-Y., Xu, W., & Deng, H.-R. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1784299
- Authors
- Roh, E., Kim, Y. A., Ku, E. J., Bae, J. H., Kim, H. M., Cho, Y. M., Park, Y. J., Park, K. S., Kim, S. Y., & Kwak, S. H.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kwak, Soo Heon
- ORCID
- Venue
- Endocrinology and Metabolism
- Publisher
- Korean Endocrine Society
- Published
- 2013
- Volume
- 28
- Issue
- 1
- Pages
- 55
- ISSN
- 2093-596X (ISSN-L)
- 2093-5978
- PMC
- PMC3811805
- OpenAlex
- W2071192234
- Cited by
- 24
- References
- 18
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 4 · 2014: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Endocrinology and Metabolism (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- insulin autoimmune syndrome, methimazole, Graves' disease, hypoglycemia, insulin autoantibodies, HLA-DRB1*0406, adverse drug reactions, antithyroid drugs, drug-induced hypoglycemia
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