Hirata Syndrome Clinical Presentation and Management
A Single-Centre Experience
DOI:
https://doi.org/10.15605/jafes.040.02.15Keywords:
Hirata syndrome, Insulin autoantibody syndrome, insulin autoantibody, HypoglycemiaAbstract
Background. Hirata syndrome, or Insulin Autoimmune Syndrome (IAS), is a rare condition characterized by hyperinsulinemic hypoglycemia due to autoantibodies targeting endogenous insulin. Its rarity and unique presentation make diagnosis and management challenging.
Objective. To analyze the clinical presentation, diagnostic methods, and management of IAS based on a single-center experience
Methodology. This was a case series, conducted at a tertiary care center in northeast India, involving six cases diagnosed between January 2022 and April 2024. Clinical histories, including drug use and comorbidities, were reviewed. Laboratory analyses during hypoglycemic episodes assessed insulin, C-peptide, β-hydroxybutyrate, and cortisol levels. Extended OGTT and 72-hour fasting tests were used when spontaneous hypoglycemia was absent. Insulin autoantibodies (IAA) confirmed the diagnosis.
Result. Six IAS cases were identified, with most linked to α-lipoic acid in multivitamins and one to methimazole. Patients experienced recurrent postprandial hypoglycemia. Elevated insulin, C-peptide, and IAA levels confirmed the diagnosis. Management included discontinuation of causative drugs, dietary changes with frequent complex carbohydrate meals, and pharmacotherapy (acarbose or prednisolone). Follow-up showed resolution of hypoglycemia and normalization of IAA levels in all patients.
Conclusion. IAS should be considered in patients with hypoglycemia and a history of sulfhydryl-containing medications. Early diagnosis using IAA measurement and appropriate management, including drug discontinuation, dietary adjustments, and pharmacotherapy, is essential. Further research is needed to refine treatment strategies and understand the pathogenesis of this rare syndrome.
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References
1. Cappellani D, Macchia E, Falorni A, Marchetti P. Insulin autoimmune syndrome (Hirata Disease): A comprehensive review fifty years after its first description. Diabetes Metab Syndr Obes. 2020;13:963-78. https://pubmed.ncbi.nlm.nih.gov/32308449 https://pmc.ncbi.nlm.nih.gov/articles/PMC7136665 https://doi.org/10.2147/DMSO.S219438 DOI: https://doi.org/10.2147/DMSO.S219438
2. Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinol Metab Clin North Am. 1999;28(3):495-500,v-vi. https://pubmed.ncbi.nlm.nih.gov/10500927 https://doi.org/10.1016/s0889-8529(05)70084-0 DOI: https://doi.org/10.1016/S0889-8529(05)70084-0
3. Lin M, Chen Y, Ning J. Insulin Autoimmune syndrome: A systematic review. Int J Endocrinol. 2023;2023:1225676. https://pubmed.ncbi.nlm.nih.gov/36844104 https://pmc.ncbi.nlm.nih.gov/articles/PMC9946739 https://doi.org/10.1155/2023/1225676 DOI: https://doi.org/10.1155/2023/1225676
4. Boro H, Gupta U, Singh C, Malhotra R, Khadgawat R. Insulin autoimmune syndrome – A case series. Eur Endocrinol. 2020;16(2):168-71. https://pubmed.ncbi.nlm.nih.gov/33117451 https://pmc.ncbi.nlm.nih.gov/articles/PMC7572167 Dhttps://doi.org/10.17925/EE.2020.16.2.168 DOI: https://doi.org/10.17925/EE.2020.16.2.168
5. Dolinina ES, Akimsheva EY, Parfenyuk EV. Development of novel silica-based formulation of α-lipoic acid: Evaluation of photo and thermal stability of the encapsulated drug. Pharmaceutics. 2020; 12(3):228. https://pubmed.ncbi.nlm.nih.gov/32143535 https://pmc.ncbi.nlm.nih.gov/articles/PMC7150826 https://doi.org/10.3390/pharmaceutics12030228. DOI: https://doi.org/10.3390/pharmaceutics12030228
6. National Center for Biotechnology Information. PubChem compound summary for CID 1349907, Methimazole. https://pubchem.ncbi.nlm.nih.gov/compound/Methimazole. Accessed June 10, 2025.
7. Sehgal T, Ohri U, Mittal N, Attri P, Dishant F. A case of insulin autoimmune syndrome in an Indian male taking alpha-lipoic acid. Cureus. 2023;15(8):e43743. https://pubmed.ncbi.nlm.nih.gov/37727171 https://pmc.ncbi.nlm.nih.gov/articles/PMC10506126 https://doi.org/10.7759/cureus.43743 DOI: https://doi.org/10.7759/cureus.43743
8. Censi S, Mian C, Betterle C. Insulin autoimmune syndrome: From diagnosis to clinical management. Ann Transl Med. 2018;6(17):335. Phttps://pubmed.ncbi.nlm.nih.gov/30306074 https://pmc.ncbi.nlm.nih.gov/articles/PMC6174196. https://doi.org/10.21037/atm.2018.07.32 DOI: https://doi.org/10.21037/atm.2018.07.32
9. Ashraf H, Mubarik I. Insulin autoimmune syndrome (Hirata’s disease) - A case report. Endocrine Abstracts. 2022; 81: EP1192. https://doi.org/10.1530/endoabs.81.EP1192 DOI: https://doi.org/10.1530/endoabs.81.EP1192
10. Censi S, Albergoni M, Gallo N, Plebani M, Boscaro M, Betterle C. Insulin autoimmune syndrome (Hirata’s disease) in an Italian patient: A case report and review of the literature. Clin Chem Lab Med. 2018;56(6): 889-95. https://pubmed.ncbi.nlm.nih.gov/28917079 https://doi.org/10.1515/cclm-2017-0392 DOI: https://doi.org/10.1515/cclm-2017-0392
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