scholarly journals Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies

2001 ◽  
pp. 311-316 ◽  
Author(s):  
B Cavaco ◽  
Y Uchigata ◽  
T Porto ◽  
M Amparo-Santos ◽  
L Sobrinho ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Blood Glucose ◽  
Polyclonal Antibody ◽  
Insulin Autoantibodies ◽  
White Female ◽  
Normal Range ◽  
Insulin Levels ◽  
Postprandial State ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan and so far only 27 IAS cases have been described from outside Asia. We describe two unrelated Portuguese patients with IAS and characterise their insulin autoantibodies and HLA alleles. PATIENTS: Patient 1, a 24-year-old white female suffered an episode of unconsciousness in the late postprandial state and blood glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml (normal range 0-30 microIU/ml). She was receiving monthly injections of penicillin G for the prophylaxis of recurrent tonsillitis. Patient 2, was a 19-year-old white female, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-56 mg/dl. Very high insulin levels (602-708 microIU/ml) were present. METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi-quantitative method, were strongly positive in both patients (91.7% in patient 1 and 88.6% in patient 2; normal range < or =7%). Sephadex G-100 chromatography of the sera showed most of insulin immunoreactivity present in the void volume which was retained by an affinity column with anti-human-immunoglobulin G antibodies (87% and 95% from patients 1 and 2 respectively). Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibody and DRB1*0403 in patient 2. CONCLUSIONS: These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.

Insulin autoimmune syndrome in a methimazole-treated Graves' patient with polyclonal anti-insulin autoantibodies

1987 ◽  
Vol 3 ◽  
pp. S39-S39
Author(s):  
YAUJIUNNLEE ◽  
SHYIJANGSHIN ◽  
JIAKANNTORNG ◽  
WENJANGLIU ◽  
YUNGHSIUNGLAI ◽  
...  
Keyword(s):  
Insulin Autoantibodies ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata’s disease) in a hypoglycemic child: a case report and review of the literature

2019 ◽  
Vol 32 (4) ◽  
pp. 421-428 ◽  
Author(s):  
Tiago Jeronimo Dos Santos ◽  
Caroline Gouvêa Buff Passone ◽  
Marina Ybarra ◽  
Simone Sakura Ito ◽  
Milena Gurgel Teles ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Previous History ◽  
Human Leukocyte ◽  
Hyperinsulinemic Hypoglycemia ◽  
Insulin Levels ◽  
Insulin Autoimmune Syndrome ◽  
Endogenous Insulin ◽  
Autoimmune Syndrome ◽  
Insulin Autoantibody ◽  
Control Food Intake

Abstract Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 μU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

scholarly journals Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome

2018 ◽  
Vol 103 (10) ◽  
pp. 3845-3855 ◽  
Author(s):  
David Church ◽  
Luís Cardoso ◽  
Richard G Kay ◽  
Claire L Williams ◽  
Bernard Freudenthal ◽  
...  
Keyword(s):  
Insulin Autoantibodies ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

Insulin autoimmune syndrome: a rare cause of spontaneous hypoglycaemia in non-diabetic individuals

2020 ◽  
Vol 13 (12) ◽  
pp. e234448
Author(s):  
Shruthi Ravindra ◽  
Sahana Shetty
Keyword(s):  
Endoscopic Ultrasound ◽  
Insulin Autoantibodies ◽  
Exogenous Insulin ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Pancreatic Tumour ◽  
Biochemical Evaluation ◽  
Antibody Levels ◽  
Hyperinsulinemic Hypoglycaemia

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycaemia, characterised by recurrent hypoglycaemic episodes secondary to insulin autoantibodies in individuals who are not exposed to exogenous insulin. We are reporting a case of IAS in a 64-year-old gentleman, who presented with predominant postprandial hypoglycaemic episodes. On biochemical evaluation, he was found to have hyperinsulinemic hypoglycaemia. Localisation studies with MRI abdomen and endoscopic ultrasound (EUS) were negative for pancreatic tumour. Tests sent for insulin antibody levels were elevated. The patient was treated with frequent meals, acarbose and glucocorticoids. Patient condition improved and did not experience hypoglycaemia on follow-up.

scholarly journals Insulin autoimmune syndrome: case report

2004 ◽  
Vol 122 (4) ◽  
pp. 178-180 ◽  
Author(s):  
Rodrigo Oliveira Moreira ◽  
Giovanna Aparecida Balarini Lima ◽  
Patrícia Carla Batista Peixoto ◽  
Maria Lucia Fleiuss Farias ◽  
Mario Vaisman
Keyword(s):  
Case Report ◽  
Pancreatic Tumor ◽  
Histopathological Examination ◽  
Severe Trauma ◽  
Insulin Antibodies ◽  
Insulin Levels ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
High Insulin ◽  
Biochemical Evaluation

CONTEXT: Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America. CASE REPORT: A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

scholarly journals Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yimin Shen ◽  
Xiaoxiao Song ◽  
Yuezhong Ren
Keyword(s):  
Diabetes Mellitus ◽  
Case Series ◽  
Insulin Injection ◽  
Insulin Autoantibodies ◽  
Hyperinsulinemic Hypoglycemia ◽  
Exogenous Insulin ◽  
Case Presentation ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Patients With Diabetes

Abstract Background Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS. Case presentation We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed. Conclusion High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.

Severe hypoglycemia due to insulin autoimmune syndrome with insulin autoantibodies crossreactive to proinsulin

2001 ◽  
Vol 109 (04) ◽  
pp. 245-248 ◽  
Author(s):  
T. Lohmann ◽  
J. Kratzsch ◽  
K. Kellner ◽  
H. Witzigmann ◽  
J. Hauss ◽  
...  
Keyword(s):  
Severe Hypoglycemia ◽  
Insulin Autoantibodies ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

scholarly journals A Curious Case of Hypoglycemia: A Rare Occurrence of Insulin Autoimmune Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A360-A361
Author(s):  
Rithikaa Ellangovan ◽  
Rachana Mundada ◽  
Ajinkya Kulkarni ◽  
Robert A Ries ◽  
Sudheer Konduru ◽  
...  
Keyword(s):  
African American ◽  
African American Male ◽  
Serum Glucose ◽  
C Peptide ◽  
Insulin Levels ◽  
Insulin Autoimmune Syndrome ◽  
Endogenous Insulin ◽  
Autoimmune Syndrome ◽  
High Insulin ◽  
Recurrent Hypoglycemia

Abstract Background: Hypoglycemia can be challenging, requiring close monitoring and evaluation. Although treating diabetes can cause hypoglycemia, the coexistence of autoimmune syndromes contributes to rare etiologies. They are characterized by elevated insulin levels with either insulin autoantibodies (IAA) or insulin receptor antibodies (IRA). It has been observed commonly in Japan but is scarce among non-Asian groups. We present a unique case of insulin autoimmune syndrome (IAS) that posed a diagnostic challenge in an African American male. Case: A 73-year-old African American male was admitted with altered mental status. Medical history included type 2 diabetes, hypertension, and hyperlipidemia. Home medications were carvedilol and simvastatin. On arrival, vital signs were normal. A fingerstick glucose was 52 mg/dL with a serum level of 68 mg/dL (70–110). Other labs were normal. Given symptomatic hypoglycemia, an IV dextrose infusion was initiated. Once his mentation improved, a diet was started. Despite this, he had recurrent hypoglycemia with glucose levels as low as 22 mg/dL, predominantly in fasting state with sporadic hyperglycemia. On rare occasions, he received correctional insulin for the same. An HbA1c was &lt;4% (4–6). Thyroid function test and AM cortisol were normal. A cosyntropin stimulation test was negative for adrenal insufficiency. A hypoglycemia panel showed inappropriately high levels of insulin, highest at 77.4 μIU/mL(&lt;=29.1), proinsulin of 19.7 pmol/L (&lt;=8), and C-peptide of 5.6 (0.8–3.69 ng/mL) when serum glucose was 25 mg/dL. An MRI abdomen was normal. Octreotide study was negative for insulinoma. He had a normal response to IM glucagon, inferring normal glycogen stores. He was started on Diazoxide 160 mg thrice a day for recurrent hypoglycemia. An endoscopic ultrasound and DOTATATE scan were negative. He had no hypoglycemia for a few days, attributable to lingering effects of diazoxide. Eventually, his serum glucose was 52 mg/dL. Labs prior to glucose correction included an insulin level elevated at 1,000 (normal &lt;3 mcIU/mL), c-peptide at 0.90 ng/mL, and proinsulin of 5.6 pmol/L. Given exceedingly high insulin levels, we measured an IAA level. This was &gt;50 u/mL (normal &lt;0.4 u/mL). With negative imaging and high IAAs, a diagnosis of IAS was made. Discussion: IAS or Hirata disease is a rare condition with hyperinsulinemic hypoglycemia and high titers of antibodies to endogenous insulin. The binding kinetics of endogenous insulin to these antibodies causes physiologically inappropriate levels of bioavailable insulin, causing either hyper- or hypoglycemia. IAA should be measured in patients with high insulin levels that are inconsistent with C peptide levels. We believe this to be the first African American patient to have been diagnosed with Hirata disease. Making a correct diagnosis may spare a hypoglycemic patient from unnecessary pancreatic surgical intervention.

scholarly journals A novel approach to a rare case of non-islet cell hypoglycaemia

2021 ◽  
Vol 2021 ◽  
Author(s):  
R K Dharmaputra ◽  
K L Wan ◽  
N Samad ◽  
M Herath ◽  
J Wong ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Islet Cell ◽  
B Lymphocyte ◽  
Serum Insulin ◽  
Insulin Antibody ◽  
Lymphocyte Depletion ◽  
Insulin Levels ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
High Insulin

Summary Insulin autoimmune syndrome (IAS) is a rare cause of non-islet cell hypoglycaemia. Treatment of this condition is complex and typically involves long-term use of glucocorticoids. Immunotherapy may provide an alternative in the management of this autoimmune condition through the suppression of antibodies production by B-lymphocyte depletion. We present a case of a 62-year-old male, with refractory hypoglycaemia initially presenting with hypoglycaemic seizure during an admission for acute psychosis. Biochemical testing revealed hypoglycaemia with an inappropriately elevated insulin and C-peptide level and no evidence of exogenous use of insulin or sulphonylurea. Polyethylene glycol precipitation demonstrated persistently elevated free insulin levels. This was accompanied by markedly elevated anti-insulin antibody (IA) titres. Imaging included CT with contrast, MRI, pancreatic endoscopic ultrasound and Ga 68-DOTATATE position emission tomography (DOTATATE PET) scan did not reveal islet cell aetiology for hyperinsulinaemia. Maintenance of euglycaemia was dependent on oral steroids and dextrose infusion. Complete resolution of hypoglycaemia and dependence on glucose and steroids was only achieved following treatment with plasma exchange and rituximab. Learning points Insulin autoimmune syndrome (IAS) should be considered in patients with recurrent hyperinsulinaemic hypoglycaemia in whom exogenous insulin administration and islet cell pathologies have been excluded. Biochemical techniques play an essential role in establishing high insulin concentration, insulin antibody titres, and eliminating biochemical interference. High insulin antibody concentration can lead to inappropriately elevated serum insulin levels leading to hypoglycaemia. Plasma exchange and B-lymphocyte depletion with rituximab and immunosuppression with high dose glucocorticoids are effective in reducing serum insulin levels and hypoglycaemia in insulin autoimmune syndrome (IAS). Based on our observation, the reduction in serum insulin level may be a better indicator of treatment efficacy compared to anti-insulin antibody (IA) titre as it demonstrated greater correlation to the frequency of hypoglycaemia and to hypoglycaemia resolution.

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