Int J Thyroidol.  2024 Nov;17(2):295-298. 10.11106/ijt.2024.17.2.295.

Methimazole-Induced Insulin Autoimmune Syndrome in a Korean Patient with Graves’ Disease Treated with Propylthiouracil: a Case Report and Literature Review

Affiliations
  • 1Division of Endocrinology, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea

Abstract

Insulin autoimmune syndrome (IAS) is rare. Herein, we report a case of methimazole-induced IAS successfully treated with propylthiouracil (PTU) and review related literature on Korean cases. A 48-year-old woman visited our hospital due to a hypoglycemic mental alteration. She had been taking medications for Graves’ disease including methimazole. Laboratory tests revealed a low serum glucose, high insulin, C-peptide, and anti-insulin antibody titer level. Abdominal computed tomography was negative for pancreatic tumors. Therefore, the patient was diagnosed with methimazole-induced IAS. After methimazole discontinuation and frequent diet, her hypoglycemic symptoms improved. She was treated with PTU for Graves’ disease. Previously, six cases of methimazole-induced IAS have been reported in Korea. Our case was the first in Korea to respond well to medical therapy (PTU) without other hypoglycemic treatments, such as steroids. PTU, which does not contain a sulfhydryl group, can be an option for the treatment of Graves’ disease and methimazole-induced IAS.

Keyword

Methimazole; Insulin autoimmune syndrome; Treatment

Reference

References

1. Shao Y, Shao F, Zhou J, Fang S, Zhu J, Li F. 2024; The association between hypoglycemia and mortality in sepsis and septic shock: a systematic review and meta-analysis. Adv Clin Exp Med. 33(3):197–205. DOI: 10.17219/acem/166656. PMID: 37386859.
2. Basu A, Service FJ, Yu L, Heser D, Ferries LM, Eisenbarth G. 2005; Insulin autoimmunity and hypoglycemia in seven white patients. Endocr Pract. 11(2):97–103. DOI: 10.4158/EP.11.2.97. PMID: 15901524.
3. Lee KS, Kim JH, Choi WH, Kim TW, Kim MH. 1993; A case report of insulin autoimmune syndrome in Graves' disease. J Korean Soc Endocrinol. 8:451–5.
4. Lim JK, Woo YA, Kang SJ, Yoo SS, Hong KY, Kim SH. 1998; Ensulin autoimmune syndrome in a patient with methimazole-treated Graves' disease: a case report. J Korean Soc Endocrinol. 13:612–6.
5. Lee SH, Oh SH, Chung WY. 2013; Insulin autoimmune syndrome in a Korean girl with Graves' disease. Ann Pediatr Endocrinol Metab. 18:32–5. DOI: 10.6065/apem.2013.18.1.32. PMID: 24904848. PMCID: PMC4027063.
6. Roh E, Kim YA, Ku EJ, Bae JH, Kim HM, Cho YM, et al. 2013; Two cases of methimazole-induced insulin autoimmune syndrome in Graves' disease. Endocrinol Metab. 28:55–60. DOI: 10.3803/EnM.2013.28.1.55. PMID: 24396652. PMCID: PMC3811805.
7. Uchigata Y, Eguchi Y, Takayama-Hasumi S, Omori Y. Insulin autoimmune syndrome (Hirata disease): clinical features and epidemiology in Japan. Diabetes Res Clin Pract. 1994; 22(2-3):89–94. DOI: 10.1016/0168-8227(94)90040-X. PMID: 8200300.
8. Woo CY, Jeong JY, Jang JE, Leem J, Jung CH, Koh EH, et al. 2015; Clinical features and causes of endogenous hyperinsulinemic hypoglycemia in Korea. Diabetes Metab J. 39(2):126–31. DOI: 10.4093/dmj.2015.39.2.126. PMID: 25922806. PMCID: PMC4411543.
9. Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P. 2009; Autoimmune forms of hypoglycemia. Medicine (Baltimore). 88(3):141–53. DOI: 10.1097/MD.0b013e3181a5b42e. PMID: 19440117.
10. Hirata Y. 1983; Methimazole and insulin autoimmune syndrome with hypoglycemia. Lancet. 2(8357):1037–8. DOI: 10.1016/S0140-6736(83)91031-0. PMID: 6138590.
11. Uchigata Y, Kuwata S, Tokunaga K, Eguchi Y, Takayama-Hasumi S, Miyamoto M, et al. 1992; Strong association of insulin autoimmune syndrome with HLA-DR4. Lancet. 339(8790):393–4. DOI: 10.1016/0140-6736(92)90080-M. PMID: 1346661.
12. Uchigata Y, Kuwata S, Tsushima T, Tokunaga K, Miyamoto M, Tsuchikawa K, et al. 1993; Patients with Graves' disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406. J Clin Endocrinol Metab. 77(1):249–54. DOI: 10.1210/jcem.77.1.8325948. PMID: 8325948.
13. Uchigata Y, Hirata Y, Omori Y, Iwamoto Y, Tokunaga K. 2000; Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles. Hum Immunol. 61(2):154–7. DOI: 10.1016/S0198-8859(99)00144-5. PMID: 10717808.
14. Eisenbarth GS. Immunoendocrinology: scientific and clinical aspects. Chapter 21. Insulin autoimmune syndrome (Hirata disease). Totowa: Springer Science+Business Media;2011. p. 343–67. DOI: 10.1007/978-1-60327-478-4_21.
15. Yaturu S, DePrisco C, Lurie A. 2004; Severe autoimmune hypoglycemia with insulin antibodies necessitating plasmapheresis. Endocr Pract. 10(1):49–54. DOI: 10.4158/EP.10.1.49. PMID: 15251622.
16. Yu L, Herold K, Krause-Steinrauf H, McGee PL, Bundy B, Pugliese A, et al. 2011; Rituximab selectively suppresses specific islet antibodies. Diabetes. 60(10):2560–5. DOI: 10.2337/db11-0674. PMID: 21831969. PMCID: PMC3178300.
Full Text Links
  • IJT
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2025 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr