Spontaneous hypoglycaemia in the presence of both anti-insulin antibody and anti-insulin receptor antibody

Bortolotti, D; Mothe-Satney, Isabelle; Ferrari, P.; Gautier, Nadine; Sonke, Jenny; Palle, Sirish; Bernard, Ghislaine; Badetti, J; Fredenrich, A.; Obberghen, Emmanuel Van; Canivet, B

doi:10.1016/s1262-3636(07)70314-2

Cited by 22 publications

(13 citation statements)

References 19 publications

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“…Rarely, the co-existence of both insulin autoantibodies and insulin receptor autoantibodies within the same patient has been described. 12 A striking feature of IAS is the magnitude of insulin elevation-with results generally above 1,000 pmol/L 13 -secondary to the insulin assay reacting with the autoantibody-bound insulin molecules. Increased insulin level to this extent is rarely seen in insulinomas.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

2013

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Insulin autoimmune syndrome (IAS) is an uncommon cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to endogenous insulin in individuals without previous exposure to exogenous insulin. IAS is the third leading cause of spontaneous hypoglycemia in Japan, and is increasingly being recognized worldwide in non-Asian populations. We report a case of IAS in a Caucasian woman with recurrent complaints of hypoglycemia, with laboratory findings of serum glucose 2.5 mmol/L (45 mg/dL), insulin 54,930 pmol/L (7,909 μIU/mL), connecting peptide (C-peptide) 4,104 pmol/L (12.4 ng/mL), and a corresponding insulin to C-peptide molar ratio of 13.4 during a spontaneous hypoglycemic event. Autoantibodies to insulin were markedly elevated at > 50 kU/L (> 50 U/mL). IAS should be considered in the differential diagnosis of hypoglycemia in non-diabetic individuals. Distinction from insulinoma is especially crucial to prevent unwarranted invasive procedures and surgical interventions in hypoglycemic patients.KEY WORDS: insulin autoimmune syndrome; hypoglycemia; insulin to C-peptide molar ratio.

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Section: Discussionmentioning

confidence: 99%

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

2013

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“…In 2002, Arioglu et al 2 reported that 7 of 13 female patients between the ages of 14 and 50 years seen at the NIH had elevated testosterone levels. 46 Shim et al, 71 Bortolotti et al, 9 and Kato et al 42 ‡It is not clear from the report whether the patient had fasting or reactive hypoglycemia. We observed a reduction in testosterone levels when the patients_ autoantibody syndrome remits, suggesting that the hyperandrogenism is associated with the presence of the autoantibody or hyperinsulinemia.…”

Section: Clinical Characteristics Of Type B Insulin Resistancementioning

confidence: 99%

Autoimmune Forms of Hypoglycemia

et al. 2009

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Autoimmune syndromes are a rare cause of hypoglycemia characterized by elevated levels of insulin in the presence of either anti-insulin antibodies (insulin autoimmune syndrome) or anti-insulin receptor antibodies (type B insulin resistance). Insulin autoimmune syndrome is the third leading cause of hypoglycemia in Japan, but has rarely been described in the non-Asian population.In the current study, we report the clinical and biochemical characteristics and clinical course of 2 white patients with insulin autoimmune syndrome, and present a literature review of non-Asian patients reported with insulin autoimmune syndrome. Also, we describe the clinical and biochemical characteristics of patients reported in the literature with type B insulin resistance who manifested hypoglycemia. We compare the clinical and laboratory features of insulin autoimmune syndrome and type B insulin resistance with each other and with other forms of hyperinsulinemic hypoglycemia.Autoimmune forms of hypoglycemia are uncommon. However, they should be considered in any patient with hypoglycemia in the setting of unsuppressed insulin levels associated with anti-insulin or anti-insulin receptor antibodies. Making the correct diagnosis may spare a hypoglycemic patient from an unnecessary pancreatic surgical procedure.

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“…This occurred sequentially [43] or in combination [44][45][46][47][48] as part of the idiotypic immune response (for more details, see [48]). The clinical and biochemical manifestations were dependent on the preponderance and characteristics of each antibody, which have the potential to make some biochemical tests, in some cases inconsistent and even confusing [43][44][45][46][47][48].…”

Section: Ias With Both Insulin/proinsulin Binding and Receptor Antibomentioning

confidence: 99%

“…The clinical and biochemical manifestations were dependent on the preponderance and characteristics of each antibody, which have the potential to make some biochemical tests, in some cases inconsistent and even confusing [43][44][45][46][47][48]. A positive test for insulin and/or proinsulin(s) binding antibodies establishes the diagnosis of IAS; additional tests for receptor antibodies were necessary to confirm this entity of IAS [74,78].…”

Section: Ias With Both Insulin/proinsulin Binding and Receptor Antibomentioning

confidence: 99%

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The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis

Ismail¹

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:Insulin autoimmune syndrome (IAS) is considered to be very rare in Caucasians. Understanding its pathophysiology is paramount in (a) appreciating its potential impact on analyses of pancreatic hormones and (b) explaining its highly variable clinical manifestations in non-diabetic, non-acutely ill patients with indeterminate hypoglycaemia. The underlying aetiology of IAS is the presence of variable affinity/avidity endogenous insulin antibodies in significant amounts. The two types of insulin antibodies namely antibodies which bind insulin and/ or proinsulin(s) and receptor antibodies (insulin mimetic) will be discussed. Their biochemical and immunological roles in causing hypoglycaemia will be highlighted. Clinical manifestations of IAS can vary from mild and transient to spontaneous, severe and protracted hypoglycaemia necessitating in extreme cases plasmapheresis for glycaemic control. Antibodies of IAS can interfere in pancreatic immunoassay tests causing erroneous and potentially misleading results. Thorough testing for endogenous insulin antibodies must be considered in the investigations of non-diabetic, non-acutely ill patients with indeterminate and/or unexplained hypoglycaemia.Keywords: endogenous insulin antibodies; Hirata's disease, insulin autoimmune hypoglycaemia; hypoglycaemia in non-diabetic; insulin autoimmune syndrome (IAS); interference in immunoassays of insulin, proinsulin and C-peptide; wrong immunoassay results .

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Spontaneous hypoglycaemia in the presence of both anti-insulin antibody and anti-insulin receptor antibody

Cited by 22 publications

References 19 publications

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

Autoimmune Forms of Hypoglycemia

The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis

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