499
Views
40
CrossRef citations to date
0
Altmetric
Review

Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description

ORCID Icon, , ORCID Icon &
Pages 963-978 | Published online: 01 Apr 2020

References

  • Hirata Y, Ishizu H, Ouchi N. Insulin autoimmunity in a case of spontaneous hypoglycemia. J Jpn Diabetes Soc. 1970;13:312–320.
  • De Pirro R, Roth RA, Rossetti L, Goldfine ID. Characterization of the serum from a patient with insulin resistance and hypoglycemia. Evidence for multiple populations of insulin receptor antibodies with different receptor binding and insulin-mimicking activities. Diabetes. 1984;33(3):301–304. doi:10.2337/diab.33.3.301
  • Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P. Autoimmune forms of hypoglycemia. Medicine (Baltimore). 2009;88(3):141–153. doi:10.1097/MD.0b013e3181a5b42e
  • Censi S, Mian C, Betterle C. Insulin autoimmune syndrome: from diagnosis to clinical management. Ann Transl Med. 2018;6(17):335. doi:10.21037/atm
  • Ishizuka T, Ogawa S, Mori T, et al. Characteristics of the antibodies of two patients who developed daytime hyperglycemia and morning hypoglycemia because of insulin antibodies. Diabetes Res Clin Pract. 2009;84(2):e21–e23. doi:10.1016/j.diabres.2009.02.007
  • Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709–728. doi:10.1210/jc.2008-1410
  • Hirata Y. Insulin Autoimmune Syndrome - the second case. J Jpn Diabetes Soc. 1972;15:187–192.
  • Folling I, Norman N. Hyperglycemia, hypoglycemic attacks, and production of anti-insulin antibodies without previous known immunization. Immunological and functional studies in a patient. Diabetes. 1972;21(7):814–826. doi:10.2337/diab.21.7.814
  • Hirata Y, Tominaga M, Ito JI, Noguchi A. Spontaneous hypoglycemia with insulin autoimmunity in Graves’ disease. Ann Intern Med. 1974;81(2):214–218. doi:10.7326/0003-4819-81-2-214
  • Oneda A, Matsuda K, Sato M, Yamagata S, Sato T. Hypoglycemia due to apparent autoantibodies to insulin. Characterization of insulin-binding protein. Diabetes. 1974;23(1):41–50. doi:10.2337/diab.23.1.41
  • Hirata Y. Methimazole and insulin autoimmune syndrome with hypoglycemia. Lancet (London, England). 1983;2(8357):1037–1038. doi:10.1016/S0140-6736(83)91031-0
  • Uchigata Y, Kuwata S, Tokunaga K, et al. Strong association of insulin autoimmune syndrome with HLA-DR4. Lancet (London, England). 1992;339(8790):393–394. doi:10.1016/0140-6736(92)90080-M
  • Uchigata Y, Hirata Y, Omori Y. A novel concept of type VII hypersensitivity introduced by insulin autoimmune syndrome (Hirata’s disease). Autoimmunity. 1995;20(3):207–208. doi:10.3109/08916939508993352
  • Uchigata Y, Hirata Y, Iwamoto Y. Drug-induced insulin autoimmune syndrome. Diabetes Res Clin Pract. 2009;83(1):e19–e20. doi:10.1016/j.diabres.2008.10.015
  • Ismail AA. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis. Clin Chem Lab Med. 2016;54(11):1715–1724. doi:10.1515/cclm-2015-1255
  • Takayama-Hasumi S, Eguchi Y, Sato A, Morita C, Hirata Y. Insulin autoimmune syndrome is the third leading cause of spontaneous hypoglycemic attacks in Japan. Diabetes Res Clin Pract. 1990;10(3):211–214. doi:10.1016/0168-8227(90)90063-Y
  • Yamada Y, Kitayama K, Oyachi M, et al. Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017-2018): congenital hyperinsulinism, insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata’s disease). J Diabetes Investig. 2019. doi:10.1111/jdi.13180
  • Woo CY, Jeong JY, Jang JE, et al. Clinical features and causes of endogenous hyperinsulinemic hypoglycemia in Korea. Diabetes Metab J. 2015;39(2):126–131. doi:10.4093/dmj.2015.39.2.126
  • Wang YL, Yao PW, Zhang XT, Luo ZZ, Wu PQ, Xiao F. Insulin autoimmune syndrome: 73 cases of clinical analysis. Chin Med J (Engl). 2015;128(17):2408–2409. doi:10.4103/0366-6999.163376
  • Uchigata Y, Hirata Y, Omori Y, Iwamoto Y, Tokunaga K. Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles. Hum Immunol. 2000;61(2):154–157. doi:10.1016/S0198-8859(99)00144-5
  • Hirata Y, Uchigata Y. Insulin autoimmune syndrome in Japan. Diabetes Res Clin Pract. 1994;24(Suppl):S153–S157. doi:10.1016/0168-8227(94)90243-7
  • 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
  • Lee SH, Oh SH, Chung WY. Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves’ disease. Ann Pediatr Endocrinol Metab. 2013;18(1):32–35. doi:10.6065/apem.2013.18.1.32
  • Alves C, Constanca J, De Leon DD, Snider K, Stanley C. A novel atypical presentation of insulin autoimmune syndrome (Hirata’s disease) in a child. J Pediatr Endocrinol Metab. 2013;26(11–12):1163–1166. doi:10.1515/jpem-2013-0215
  • Su CT, Lin YC. Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog. Endocrinol Diabetes Metab Case Rep. 2016;2016:16–0079.
  • Kobayashi S, Amano H, Kawaguchi Y, Yokoo T. A novel treatment of hyperinsulinemic hypoglycemia induced by insulin antibodies with alkali administration: a case report. J Med Case Rep. 2019;13(1):79. doi:10.1186/s13256-019-1989-8
  • Chen F, Yang J, Liu Y, et al. Insulin autoimmune syndrome: three case reports. Medicine (Baltimore). 2018;97(51):e13486. doi:10.1097/MD.0000000000013486
  • Betterle C, Zanchetta R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed. 2003;74(1):9–33.
  • Takei M. Insulin auto-antibodies produced by methimazole treatment in the patients with the Graves’ disease. J Tokyo Women’s Med Coll. 1980;50:54.
  • Uchigata Y, Omori Y, Nieda M, Kuwata S, Tokunaga K, Juji T. HLA-DR4 genotype and insulin-processing in insulin autoimmune syndrome. Lancet (London, England). 1992;340(8833):1467. doi:10.1016/0140-6736(92)92654-X
  • Uchigata Y, Tokunaga K, Nepom G, et al. Differential immunogenetic determinants of polyclonal insulin autoimmune syndrome (Hirata’s disease) and monoclonal insulin autoimmune syndrome. Diabetes. 1995;44(10):1227–1232. doi:10.2337/diab.44.10.1227
  • Uchigata Y, Kuwata S, Tsushima T, et al. Patients with Graves’ disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406. J Clin Endocrinol Metab. 1993;77(1):249–254. doi:10.1210/jcem.77.1.8325948
  • Uchigata Y. The novel agent, alpha lipoic acid, can cause the development of insulin autoimmune syndrome. Intern Med. 2007;46(17):1321–1322. doi:10.2169/internalmedicine.46.0221
  • Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking alpha-lipoic acid. Clin Endocrinol (Oxf). 2014;81(2):204–209. doi:10.1111/cen.12334
  • Cappellani D, Sardella C, Campopiano MC, Falorni A, Marchetti P, Macchia E. Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid. Endocrinol Diabetes Metab Case Rep. 2018;2018:18–0122.
  • Reis MZR, Fernandes VO, Fontenele EGP, et al. Insulin autoimmune syndrome in an occidental woman: a case report and literature review. Arch Endocrinol Metab. 2018;62(5):566–570. doi:10.20945/2359-3997000000078
  • Zhang Y, Zhao T. Hypoglycemic coma due to insulin autoimmune syndrome induced by methimazole: a rare case report. Exp Ther Med. 2014;8(5):1581–1584. doi:10.3892/etm.2014.1964
  • Basu A, Service FJ, Yu L, Heser D, Ferries LM, Eisenbarth G. Insulin autoimmunity and hypoglycemia in seven white patients. Endocr Pract. 2005;11(2):97–103. doi:10.4158/EP.11.2.97
  • Hakamata M, Itoh M, Sudo Y, Miyata N. Insulin autoimmune syndrome after the third therapy with methimazole. Intern Med. 1995;34(5):410–412. doi:10.2169/internalmedicine.34.410
  • Jain N, Savani M, Agarwal M, Kadaria D. Methimazole-induced insulin autoimmune syndrome. Ther Adv Endocrinol Metab. 2016;7(4):178–181. doi:10.1177/2042018816658396
  • Gomez Cruz MJ, Jabbar M, Saini N, et al. Severe hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in a 16 year old African-American male. Pediatr Diabetes. 2012;13(8):652–655. doi:10.1111/pedi.2012.13.issue-8
  • Virally ML, Timsit J, Chanson P, Warnet A, Guillausseau PJ. Insulin autoimmune syndrome: a rare cause of hypoglycaemia not to be overlooked. Diabetes Metab. 1999;25(5):429–431.
  • Mettananda C, de Silva HJ, Fernando R. Hypoglycaemia and fits in a thyrotoxic man. BMJ Case Rep. 2009;2009. doi:10.1136/bcr.07.2008.0448
  • Wong ST, Ng WY, Thai AC. Case report: autoimmune insulin syndrome in a Chinese female with Graves’ disease. Ann Acad Med Singapore. 1996;25(6):882–885.
  • Lu CC, Lee JK, Lam HC, Yang CY, Han TM. Insulin autoimmune syndrome in a patient with methimazole and carbimazole-treated Graves’ disease: a case report. Zhonghua Yi Xue Za Zhi (Taipei). 1994;54(5):353–358.
  • Armitage M, Franklyn J, Scott-Morgan L, et al. Insulin autoantibodies in Graves’ disease–before and after carbimazole therapy. Diabetes Res Clin Pract. 1990;8(3):169–176. doi:10.1016/0168-8227(90)90113-8
  • Lin HD, Chen HD, Chang PY, Lin CY, Ching KN. Insulin autoimmune syndrome in methimazole or carbimazole treated Chinese patients of Graves’ disease. Zhonghua Yi Xue Za Zhi (Taipei). 1988;42(3):163–168.
  • Furukawa N, Miyamura N, Nishida K, Motoshima H, Taketa K, Araki E. Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract. 2007;75(3):366–367. doi:10.1016/j.diabres.2006.07.005
  • Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. Intern Med. 2007;46(5):237–239. doi:10.2169/internalmedicine.46.1893
  • Izzo V, Greco C, Corradini D, et al. Insulin autoimmune syndrome in an Argentine woman taking alpha-lipoic acid: A case report and review of the literature. SAGE Open Med Case Rep. 2018;6:2050313X18819601.
  • Bresciani E, Bussi A, Bazzigaluppi E, Balestrieri G. Insulin autoimmune syndrome induced by alpha-lipoic acid in a Caucasian woman: case report. Diabetes Care. 2011;34(9):e146. doi:10.2337/dc11-0600
  • Ishida Y, Ohara T, Okuno Y, et al. Alpha-lipoic acid and insulin autoimmune syndrome. Diabetes Care. 2007;30(9):2240–2241. doi:10.2337/dc07-0689
  • Archambeaud-Mouveroux F, Canivet B, Fressinaud C, de Buhan B, Treves R, Laubie B. Autoimmune hypoglycemia: the fault of pyritinol? Presse Med. 1988;17(34):1733–1736.
  • Canivet B, Archambeaud F. Pyrithioxine and hypoglycemic autoimmune syndrome. Autoimmunity. 1988;1(4):321–322. doi:10.3109/08916938809010686
  • Deguchi A, Okauchi Y, Suehara S, Mineo I. Insulin autoimmune syndrome in a health supplement user: the effectiveness of cornstarch therapy for treating hypoglycemia. Intern Med. 2013;52(3):369–372. doi:10.2169/internalmedicine.52.7844
  • Blackshear PJ, Rotner HE, Kriauciunas KA, Kahn CR. Reactive hypoglycemia and insulin autoantibodies in drug-induced lupus erythematosus. Ann Intern Med. 1983;99(2):182–184. doi:10.7326/0003-4819-99-2-182
  • Burch HB, Clement S, Sokol MS, Landry F. Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review. Am J Med. 1992;92(6):681–685. doi:10.1016/0002-9343(92)90787-C
  • Yamada E, Okada S, Saito T, Osaki A, Ozawa A, Yamada M. Insulin autoimmune syndrome during the administration of clopidogrel. J Diabetes. 2016;8(4):588–589. doi:10.1111/1753-0407.12385
  • Rajpal A, Kassem LS, Moscoso-Cordero M, Arafah BM. Clopidogrel-induced insulin autoimmune syndrome: a newly recognized cause of hypoglycemia in a patient without diabetes. J Endocr Soc. 2017;1(9):1217–1223. doi:10.1210/js.2017-00316
  • Feng X, Yuan L, Hu Y, et al. Gliclazide-induced insulin autoimmune syndrome: a rare case report and review on literature. Endocr Metab Immune Disord Drug Targets. 2016;16(4):230–234. doi:10.2174/1871530316666161223144558
  • Okazaki-Sakai S, Yoshimoto S, Yagi K, Wakasugi T, Takeda Y, Yamagishi M. Insulin autoimmune syndrome caused by an adhesive skin patch containing loxoprofen-sodium. Intern Med. 2013;52(21):2447–2451. doi:10.2169/internalmedicine.52.0570
  • Benson EA, Ho P, Wang C, Wu PC, Fredlund PN, Yueng RT. Insulin autoimmunity as a cause of hypoglycemia. Arch Intern Med. 1984;144(12):2351–2354. doi:10.1001/archinte.1984.00350220067015
  • Herranz L, Rovira A, Grande C, et al. Autoimmune insulin syndrome in a patient with progressive systemic sclerosis receiving penicillamine. Horm Res. 1992;37(1–2):78–80. doi:10.1159/000182286
  • Lidar M, Rachmani R, Half E, Ravid M. Insulin autoimmune syndrome after therapy with imipenem. Diabetes Care. 1999;22(3):524–525. doi:10.2337/diacare.22.3.524a
  • Cavaco B, Uchigata Y, Porto T, Amparo-Santos M, Sobrinho L, Leite V. Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies. Eur J Endocrinol. 2001;145(3):311–316. doi:10.1530/eje.0.1450311
  • Ma WY, Won JG, Tang KT, Lin HD. Severe hypoglycemic coma due to insulin autoimmune syndrome. J Chin Med Assoc. 2005;68(2):82–86. doi:10.1016/S1726-4901(09)70140-6
  • Gopal K, Priya G, Gupta N, Praveen EP, Khadgawat R. A case of autoimmune hypoglycemia outside Japan: rare, but in the era of expanding drug-list, important to suspect. Indian J Endocrinol Metab. 2013;17(6):1117–1119. doi:10.4103/2230-8210.122644
  • Sahni P, Trivedi N, Omer A. Insulin Autoimmune Syndrome: a rare cause of postprandial hypoglycemia. Endocrinol Diabetes Metab Case Rep. 2016;2016:16–0064.
  • Kamei S, Kaneto H, Shigemoto R, et al. Human serum albumin: possible cause of insulin autoimmune syndrome. J Diabetes Investig. 2016;7(6):919–920. doi:10.1111/jdi.2016.7.issue-6
  • Papanas N, Ziegler D. Efficacy of alpha-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother. 2014;15(18):2721–2731. doi:10.1517/14656566.2014.972935
  • Vallianou N, Evangelopoulos A, Koutalas P. Alpha-lipoic acid and diabetic neuropathy. Rev Diabet Stud. 2009;6(4):230–236. doi:10.1900/RDS.2009.6.230
  • Pieralice S, Vari R, Minutolo A, et al. Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy. Endocrine. 2019;66(2):178–184. doi:10.1007/s12020-019-01917-w
  • Fruzzetti F, Fidecicchi T, Palla G, Gambacciani M. Long-term treatment with alpha-lipoic acid and myo-inositol positively affects clinical and metabolic features of polycystic ovary syndrome. Gynecol Endocrinol. 2020;36(2):152–155. doi:10.1080/09513590.2019.1640673
  • Holmquist L, Stuchbury G, Berbaum K, et al. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol Ther. 2007;113(1):154–164. doi:10.1016/j.pharmthera.2006.07.001
  • Hattori N, Duhita MR, Mukai A, Matsueda M, Shimatsu A. Development of insulin antibodies and changes in titers over a long-term period in patients with type 2 diabetes. Clin Chim Acta. 2014;433:135–138. doi:10.1016/j.cca.2014.03.008
  • Matsushita S, Takahashi K, Motoki M, Komoriya K, Ikagawa S, Nishimura Y. Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and -DRB1*0406 complexes: implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome. J Exp Med. 1994;180(3):873–883. doi:10.1084/jem.180.3.873
  • Halsall DJ, Mangi M, Soos M, et al. Hypoglycemia due to an insulin binding antibody in a patient with an IgA-kappa myeloma. J Clin Endocrinol Metab. 2007;92(6):2013–2016. doi:10.1210/jc.2007-0075
  • Church D, Cardoso L, Bradbury S, et al. Diagnosis of insulin autoimmune syndrome using polyethylene glycol precipitation and gel filtration chromatography with ex vivo insulin exchange. Clin Endocrinol (Oxf). 2017;86(3):347–353. doi:10.1111/cen.2017.86.issue-3
  • Moreira RO, Lima GA, Peixoto PC, Farias ML, Vaisman M. Insulin autoimmune syndrome: case report. Sao Paulo Med J. 2004;122(4):178–180. doi:10.1590/S1516-31802004000400010
  • Elias D, Cohen IR, Schechter Y, Spirer Z, Golander A. Antibodies to insulin receptor followed by anti-idiotype. Antibodies to insulin in child with hypoglycemia. Diabetes. 1987;36(3):348–354. doi:10.2337/diab.36.3.348
  • Eguchi Y. Scatchard analysis of insulin autoantibodies in the insulin autoimmune syndrome. J Tokyo Women’s Med Coll. 1989;59:1286–1305.
  • Iizuka K, Tomita R, Horikawa Y, Takeda J. A case of glycemic instability and insulin allergy due to anti-insulin antibodies in a patient with type 2 diabetes. Diabetol Int. 2012;3(4):233–238. doi:10.1007/s13340-012-0077-8
  • Tamura Y, Kimbara Y, Funatsuki S, et al. A case of insulin antibody-induced glucose instability in an elderly woman with type 2 diabetes on hemodialysis, successfully ameliorated with liraglutide. Diabetol Int. 2013;4(1):71–75. doi:10.1007/s13340-012-0100-0
  • Sodoyez JC, Sodoyez-Goffaux F, Koch M, et al. Clonally restricted insulin autoantibodies in a cohort of 2200 healthy blood donors. Diabetologia. 1990;33(12):719–725. doi:10.1007/BF00400341
  • Redmon JB, Nuttall FQ. Autoimmune hypoglycemia. Endocrinol Metab Clin North Am. 1999;28(3):603–618, vii. doi:10.1016/S0889-8529(05)70090-6
  • Ismail AA. The double whammy of endogenous insulin antibodies in non-diabetic subjects. Clin Chem Lab Med. 2008;46(2):153–156. doi:10.1515/CCLM.2008.031
  • Uchigata Y, Hirata Y. Insulin autoimmune syndrome (IAS, Hirata disease). Ann Med Interne (Paris). 1999;150(3):245–253.
  • Martens P, Tits J. Approach to the patient with spontaneous hypoglycemia. Eur J Intern Med. 2014;25(5):415–421. doi:10.1016/j.ejim.2014.02.011
  • Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest. 2007;117(4):868–870. doi:10.1172/JCI31669
  • Vogeser M, Parhofer KG, Furst H, Jacob K, Brodl UC, Seidel D. Autoimmune hypoglycemia presenting as seizure one week after surgery. Clin Chem. 2001;47(4):795–796. doi:10.1093/clinchem/47.4.795
  • Wong SL, Priestman A, Holmes DT. Recurrent hypoglycemia from insulin autoimmune syndrome. J Gen Intern Med. 2014;29(1):250–254. doi:10.1007/s11606-013-2588-9
  • International Hypoglycaemia Study G. Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care. 2017;40(1):155–157. doi:10.2337/dc16-2215
  • Ratner RE. Hypoglycemia: new Definitions and Regulatory Implications. Diabetes Technol Ther. 2018;20(S2):S250–S253. doi:10.1089/dia.2018.0113
  • Yuan T, Li J, Li M, et al. Insulin autoimmune syndrome diagnosis and therapy in a single chinese center. Clin Ther. 2019;41(5):920–928. doi:10.1016/j.clinthera.2019.03.009
  • Censi S, Albergoni MP, 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):889–895. doi:10.1515/cclm-2017-0392
  • Owen WE, Roberts WL. Cross-reactivity of three recombinant insulin analogs with five commercial insulin immunoassays. Clin Chem. 2004;50(1):257–259. doi:10.1373/clinchem.2003.026625
  • Marks V, Teale JD. Drug-induced hypoglycemia. Endocrinol Metab Clin North Am. 1999;28(3):555–577. doi:10.1016/S0889-8529(05)70088-8
  • Lebowitz MR, Blumenthal SA. The molar ratio of insulin to C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. Arch Intern Med. 1993;153(5):650–655. doi:10.1001/archinte.1993.00410050082011
  • Ismail AA. Testing for insulin antibodies is mandatory in the differential diagnosis of hypoglycaemia in nondiabetic subjects. Clin Endocrinol (Oxf). 2012;76(4):603–604. doi:10.1111/cen.2012.76.issue-4
  • Scatchard G. The attractions of proteins for small molecules and ions. Ann N Y Acad Sci. 1949;51(4):660–672. doi:10.1111/nyas.1949.51.issue-4
  • Eguchi Y, Uchigata Y, Yao K, Yokoyama H, Hirata Y, Omori Y. Longitudinal changes of serum insulin concentration and insulin antibody features in persistent insulin autoimmune syndrome (Hirata’s disease). Autoimmunity. 1994;19(4):279–284. doi:10.3109/08916939409071354
  • Service FJ, McMahon MM, O’Brien PC, Ballard DJ. Functioning insulinoma–incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc. 1991;66(7):711–719. doi:10.1016/S0025-6196(12)62083-7
  • Grimaldi F, Fazio N, Attanasio R, et al. Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. J Endocrinol Invest. 2014;37(9):875–909. doi:10.1007/s40618-014-0119-0
  • Mehrabi A, Fischer L, Hafezi M, et al. A systematic review of localization, surgical treatment options, and outcome of insulinoma. Pancreas. 2014;43(5):675–686. doi:10.1097/MPA.0000000000000110
  • Service FJ, Natt N, Thompson GB, et al. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J Clin Endocrinol Metab. 1999;84(5):1582–1589. doi:10.1210/jcem.84.5.5645
  • Thompson GB, Service FJ, Andrews JC, et al. Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients. Surgery. 2000;128(6):937–944;discussion 944–935. doi:10.1067/msy.2000.110243
  • Malik S, Mitchell JE, Steffen K, et al. Recognition and management of hyperinsulinemic hypoglycemia after bariatric surgery. Obes Res Clin Pract. 2016;10(1):1–14. doi:10.1016/j.orcp.2015.07.003
  • Ritz P, Hanaire H. Post-bypass hypoglycaemia: a review of current findings. Diabetes Metab. 2011;37(4):274–281. doi:10.1016/j.diabet.2011.04.003
  • Marks V, Teale JD. Hypoglycemia: factitious and felonious. Endocrinol Metab Clin North Am. 1999;28(3):579–601. doi:10.1016/S0889-8529(05)70089-X
  • Service FJ, Palumbo PJ. Factitial hypoglycemia. Three cases diagnosed on the basis of insulin antibodies. Arch Intern Med. 1974;134(2):336–340. doi:10.1001/archinte.1974.00320200146022
  • Arioglu E, Andewelt A, Diabo C, Bell M, Taylor SI, Gorden P. Clinical course of the syndrome of autoantibodies to the insulin receptor (type B insulin resistance): a 28-year perspective. Medicine (Baltimore). 2002;81(2):87–100. doi:10.1097/00005792-200203000-00001
  • Chu JP, Zheng XW, Lu J, et al. Insulin-induced autoimmune syndrome: A case report. Exp Ther Med. 2016;12(5):3359–3362. doi:10.3892/etm.2016.3767
  • Philippon M, Sejil S, Mugnier M, et al. Use of the continuous glucose monitoring system to treat insulin autoimmune syndrome: quantification of glucose excursions and evaluation of treatment efficacy. Diabet Med. 2014;31(7):e20–e24. doi:10.1111/dme.2014.31.issue-7
  • Savas-Erdeve S, Yilmaz Agladioglu S, Onder A, et al. An uncommon cause of hypoglycemia: insulin autoimmune syndrome. Horm Res Paediatr. 2014;82(4):278–282. doi:10.1159/000362758
  • Schlemper RJ, Uchigata Y, Frolich M, Vingerhoeds AC, Meinders AE. Recurrent hypoglycaemia caused by the insulin autoimmune syndrome: the first Dutch case. Neth J Med. 1996;48(5):188–192. doi:10.1016/0300-2977(95)00085-2
  • Church D, Cardoso L, Kay RG, et al. Assessment and management of anti-insulin autoantibodies in varying presentations of insulin autoimmune syndrome. J Clin Endocrinol Metab. 2018;103(10):3845–3855. doi:10.1210/jc.2018-00972
  • Paiva ES, Pereira AE, Lombardi MT, et al. Insulin autoimmune syndrome (Hirata disease) as differential diagnosis in patients with hyperinsulinemic hypoglycemia. Pancreas. 2006;32(4):431–432. doi:10.1097/01.mpa.0000220872.18153.72
  • Panikar V, Joshi S, Vadgama J, et al. Autoimmune hypoglycemia relapse on glucocorticoids, effectively treated with azathioprine. J Assoc Physicians India. 2018;66(12):78–79.
  • Saxon DR, McDermott MT, Michels AW. Novel management of insulin autoimmune syndrome with rituximab and continuous glucose monitoring. J Clin Endocrinol Metab. 2016;101(5):1931–1934. doi:10.1210/jc.2016-1097
  • Church D, Hunter RW, Lyall M, et al. Resolution of Hypoglycemia and Cardiovascular Dysfunction After Rituximab Treatment of Insulin Autoimmune Syndrome. Diabetes Care. 2017;40(7):e80–e82. doi:10.2337/dc17-0264
  • Kroemer TM, Erler A, Tsourdi E, et al. Immunoadsorption followed by rituximab as a definitive treatment for insulin autoimmune syndrome (Hirata Syndrome): a case report. Diabetes Care. 2018;41(3):e23–e24. doi:10.2337/dc17-1974
  • Yu L, Herold K, Krause-Steinrauf H, et al. Rituximab selectively suppresses specific islet antibodies. Diabetes. 2011;60(10):2560–2565. doi:10.2337/db11-0674
  • Dozio N, Scavini M, Beretta A, et al. Imaging of the buffering effect of insulin antibodies in the autoimmune hypoglycemic syndrome. J Clin Endocrinol Metab. 1998;83(2):643–648. doi:10.1210/jcem.83.2.4599
  • Yaturu S, DePrisco C, Lurie A. Severe autoimmune hypoglycemia with insulin antibodies necessitating plasmapheresis. Endocr Pract. 2004;10(1):49–54. doi:10.4158/EP.10.1.49
  • Beck RW, Riddlesworth T, Ruedy K, et al. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. JAMA. 2017;317(4):371–378. doi:10.1001/jama.2016.19975
  • Kudva YC, Ahmann AJ, Bergenstal RM, et al. Approach to using trend arrows in the freestyle libre flash glucose monitoring systems in adults. J Endocr Soc. 2018;2(12):1320–1337. doi:10.1210/js.2018-00294