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Insulin autoimmune syndrome

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Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia also known as Hirata’s disease,[1] was first described by Hirata in Japan in 1970.[2]

Signs and symptoms

Affected patients are usually adults, experiencing multiple episodes of spontaneous hypoglycemia with neuroglycopenic symptoms.[3]

Causes

The cause of IAS is not clearly understood. However, interaction of disulfide bond in the insulin molecule with sulfhydryl group drugs such as methimazole, carbimazole, captopril, isoniazid, hydralazine, imipenem, and also with lipoic acid has been suggested.[4][5][6] Drug-induced autoimmunization is evidenced by insulin autoantibodies appearing a few weeks after the intake of drug containing the sulfhydryl group. Additionally, IAS has a significant genetic predisposition as its association with specific HLA class has been observed [citation needed].

Pathophysiology

Following a meal, glucose concentration in the bloodstream rises, providing a stimulus for insulin secretion. Autoantibodies bind to these insulin molecules, rendering them unable to exert their effects. The resultant hyperglycemia promotes further insulin release. As glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. Now insulin molecules spontaneously dissociate from the autoantibodies, giving rise to a raised free insulin level inappropriate for the glucose concentration, causing hypoglycemia.[7][8]

Diagnosis

Usual presenting features are multiple episodes of spontaneous hypoglycemia and appearance of insulin autoantibodies without prior history of administration of exogenous insulin.[9] The insulin level is significantly high, usually up to 100 mIU/L, C-peptide level is markedly elevated, and insulin antibodies are positive.[citation needed]

Treatment

The best known treatment is recommending frequent, small meals and to avoid simple sugars. Sulfhydryl group-containing drugs should be avoided and steroids can be used in resistant cases.[10][11]

References

  1. ^ Alves, Cresio; Constança, Julia; De León, Diva D.; Snider, Kara; Stanley, Charles (2013). "A novel atypical presentation of insulin autoimmune syndrome (Hirata's disease) in a child". Journal of Pediatric Endocrinology and Metabolism. 26 (11–12): 1163–1166. doi:10.1515/jpem-2013-0215. PMC 4361817. PMID 23843578.
  2. ^ Y., Hirata (1970). "Insulin autoimmunity in a case of spontaneous hypoglycemia". J Jpn Diabet Soc. 13: 312–319.
  3. ^ JB, Redmon; FQ, Nuttall (1999). "Autoimmune hypoglycemia". Endocrinol Metab Clin North Am. 28 (3): 603–618. doi:10.1016/S0889-8529(05)70090-6. PMID 10500933.
  4. ^ T, Yamada; J, Imai; Y, Ishigaki; Y, Hinokio; Y, Oka; H, Katagiri (2007). "Possible relevance of HLA-DRB1*0403 haplotype in insulin autoimmune syndrome induced by alpha-lipoic acid, used as a dietary supplement". Diabetes Care. 30 (12): 131. doi:10.2337/dc07-1636. PMID 18042740.
  5. ^ Y, Uchigata; Y, Hirata; Y, Iwamoto (2009). "Drug-induced insulin autoimmune syndrome". Diabetes Res Clin Pract. 83 (1): 19–20. doi:10.1016/j.diabres.2008.10.015. PMID 19070385.
  6. ^ BC, Lupsa; AY, Chong; EK, Cochran; MA, Soos; RK, Semple; P, Gorden (2009). "Autoimmune forms of hypoglycemia". Medicine (Baltimore). 88 (3): 141–153. doi:10.1097/MD.0b013e3181a5b42e. PMID 19440117. S2CID 34429211.
  7. ^ JB, Redmon; FQ, Nuttall (1999). "Autoimmune hypoglycemia". Endocrinol Metab Clin North Am. 28 (3): 603–618. doi:10.1016/S0889-8529(05)70090-6. PMID 10500933.
  8. ^ V, Pant; B, Bhandari; S, Baral; SR, Bajracharya (7 February 2019). "Insulin autoimmune syndrome as a cause of recurrent hypoglycemia in a carbimazole user: a case report from Nepal". International Medical Case Reports Journal. 2019 (12): 29–32. doi:10.2147/IMCRJ.S190908. PMC 6369838. PMID 30799961. {{cite journal}}: External link in |ref= (help)CS1 maint: unflagged free DOI (link)
  9. ^ Y., Uchigata (1999). "Insulin autoimmune syndrome (IAS, Hirata disease)". Ann Med Interne (Paris). 150: 245–253.
  10. ^ AA, Ismail (2016). "The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis". Clin Chem Lab Med. 54 (11): 1715–1724. doi:10.1515/cclm-2015-1255. PMID 27071154. S2CID 33482503.
  11. ^ V, Pant; B, Bhandari; S, Baral; SR, Bajracharya (7 February 2019). "Insulin autoimmune syndrome as a cause of recurrent hypoglycemia in a carbimazole user: a case report from Nepal". International Medical Case Reports Journal. 2019 (12): 29–32. doi:10.2147/IMCRJ.S190908. PMC 6369838. PMID 30799961. {{cite journal}}: External link in |ref= (help)CS1 maint: unflagged free DOI (link)
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