Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole

Abstract

What is known and Objective The number of case reports of insulin autoimmune syndrome (IAS) induced by methimazole (MMI) is increasing. The purpose of this study is to explore the clinical characteristics and provide a scientific reference for clinical diagnosis, treatment and prevention. Methods The literature on IAS cases and case series induced by MMI in Chinese and English was collected for retrospective analysis. Results and discussion A total of 106 patients (males 33, females 73) were described in the Chinese and English literature. The median age of patients with IAS induced by MMI was 37 years (range 15‐76) occurring during both regular and irregular MMI therapy or after resumption of medication. The onset of symptoms occurred at night or early morning, within days in some and up to 6 months in others; the symptoms were neuropathic in 65.31% and related to the autonomic nervous system in 33.67%. Blood glucose concentration in samples presumably taken during the hypoglycaemic phase was 1.7 mmol/L (median; range 0.03‐4.7); insulin concentrations were elevated ≥100 mU/L (ref range) and associated with low C‐peptide levels (<10 μg/L; ref range). Tests for IgG insulin autoantibodies (IAA) were positive in 104 patients (98.02%) and negative in two patients (1.98%). The 75‐g oral glucose tolerance test (OGTT) showed impaired glucose tolerance and diabetic curves. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Withdrawal of MMI alone or with corticosteroid treatment reduced hypoglycaemic episodes within days to 3 months. IAA decreased and became negative in 3 months (median; range 1‐12). Follow‐up showed no recurrent hypoglycaemic episodes at 5 months (median; range 1‐60). What is new and Conclusion Methimazole‐induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment that should be treated promptly.

Insulin Autoimmune Syndrome: A Systematic Review

“…At present, the treatment plan for insulin syndrome has not been unified, and various treatment plans have been proposed in various studies, including drug withdrawal, frequent small meals, avoidance of monosaccharide intake, glucocorticoid treatment [ 59 , 60 ], plasma exchange [ 61 ], immunosuppressive agents (such as sulfur azathioprine [ 56 ] and 6-mercaptopurine), and rituximab [ 56 , 61 , 62 ] ( Table 6 ).…”

Nine‐year‐old boy with goitre, blepharoptosis and alopecia areata

“…Some drugs may cause positive insulin antibodies, mainly after the use of drugs containing sulfhydryl groups, such as methimazole, α‐lipoic acid, glutathione, imipenem and penicillin. This disease is called insulin autoimmune syndrome 6 . Therefore, it cannot be ruled out that the increase in insulin autoantibodies was associated with the use of methimazole.…”

“…This disease is called insulin autoimmune syndrome. 6 Therefore, it cannot be ruled out that the increase in insulin autoantibodies was associated with the use of methimazole. The changes in blood glucose and HbA1c are observed for a long time and no drug treatment is given for the time being.…”

Long-term follow-up of methimazole-associated insulin autoimmune syndrome: a rare case report

“…This disease is strongly associated with certain alleles of the human leukocyte antigen gene (HLA) 2 and develops in genetically predisposed individuals taking drugs containing sulfhydryl groups. [2][3][4] Methimazole (MTZ), which has a sulfhydryl group, is the preferred initial therapy for patients with Graves' disease worldwide, accounting for the higher incidence of MTZ-induced IAS in patients with than without Graves' disease. From 1985 to June 2019, 95 cases of MTZ-induced IAS were reported in China, of which only 6 cases were examined for the role of genetic predisposition.…”