Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description
Daniele Cappellani,1 Enrico Macchia,1 Alberto Falorni,2 Piero Marchetti3 1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy; 2Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perug...
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Dove Medical Press
2020-04-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/insulin-autoimmune-syndrome-hirata-disease-a-comprehensive-review-fift-peer-reviewed-article-DMSO |
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| author | Cappellani D Macchia E Falorni A Marchetti P |
| author_facet | Cappellani D Macchia E Falorni A Marchetti P |
| author_sort | Cappellani D |
| collection | DOAJ |
| description | Daniele Cappellani,1 Enrico Macchia,1 Alberto Falorni,2 Piero Marchetti3 1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy; 2Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy; 3Department of Clinical and Experimental Medicine, Division of Metabolism and Cell Transplantation, University of Pisa, Pisa, ItalyCorrespondence: Daniele CappellaniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Ospedale Cisanello, via Paradisa 2, Pisa 56124, ItalyTel +39 50 995001Fax +39 50 578772Email d.cappellani@hotmail.itAbstract: Insulin autoimmune syndrome (IAS), also named Hirata’s disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.Keywords: insulin autoimmune syndrome, IAS, Hirata, hypoglycemia, autoimmunity |
| first_indexed | 2024-04-10T18:25:19Z |
| format | Article |
| id | doaj.art-31a71e4aa5d944478be5f6c8d04b3445 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T18:25:19Z |
| publishDate | 2020-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-31a71e4aa5d944478be5f6c8d04b34452023-02-02T06:01:51ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072020-04-01Volume 1396397852864Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First DescriptionCappellani DMacchia EFalorni AMarchetti PDaniele Cappellani,1 Enrico Macchia,1 Alberto Falorni,2 Piero Marchetti3 1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy; 2Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy; 3Department of Clinical and Experimental Medicine, Division of Metabolism and Cell Transplantation, University of Pisa, Pisa, ItalyCorrespondence: Daniele CappellaniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Ospedale Cisanello, via Paradisa 2, Pisa 56124, ItalyTel +39 50 995001Fax +39 50 578772Email d.cappellani@hotmail.itAbstract: Insulin autoimmune syndrome (IAS), also named Hirata’s disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.Keywords: insulin autoimmune syndrome, IAS, Hirata, hypoglycemia, autoimmunityhttps://www.dovepress.com/insulin-autoimmune-syndrome-hirata-disease-a-comprehensive-review-fift-peer-reviewed-article-DMSOinsulin autoimmune syndromeiashiratahypoglycemia. autoimmunity |
| spellingShingle | Cappellani D Macchia E Falorni A Marchetti P Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description Diabetes, Metabolic Syndrome and Obesity insulin autoimmune syndrome ias hirata hypoglycemia. autoimmunity |
| title | Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description |
| title_full | Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description |
| title_fullStr | Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description |
| title_full_unstemmed | Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description |
| title_short | Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description |
| title_sort | insulin autoimmune syndrome hirata disease a comprehensive review fifty years after its first description |
| topic | insulin autoimmune syndrome ias hirata hypoglycemia. autoimmunity |
| url | https://www.dovepress.com/insulin-autoimmune-syndrome-hirata-disease-a-comprehensive-review-fift-peer-reviewed-article-DMSO |
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