7375 Severe Hypoglycemia In Graves’ Hyperthyroidism: A Rare Consequence Of Methimazole Induced Insulin Autoimmune Syndrome

Abstract Disclosure: J. Ratnasingam: None. N. Ismail: None. Y. Ng: None. T. Sarvanandan: None. N. Hee: None. Q. Lim: None. L. Lim: None. S. Paramasivam: None. P. Sthaneshwar: None. S. Vethakkan: None. Background: Islet autoimmune syndrome (IAS) is a rare disease characterized by elevated insulin autoantibodies (IAA), triggered by genetic, environmental or drug (sulfhydryl containing) factors. We describe a case of Graves’ hyperthyroidism who developed IAS with methimazole. Clinical Case: A 28-year-old Malaysian-Chinese woman presented with tremors and palpitations. She weighed 56 kg, had no palpable goiter or thyroid eye signs. The diagnosis of Graves’ disease was confirmed with ft4 66.5 (11.5-22.7)pmol/L and TSH <0.01 (0.55-4.78)mIU/L with elevated thyroid stimulating immunoglobulin of 5.4 (< 0.55)IU/L. She was treated with methimazole 20mg BID and Propranolol 20mg TID. After 5 weeks of methimazole, she experienced recurrent episodes of sweating and presented with a generalized tonic-clonic seizure with capillary blood glucose of 27mg/dL. Seizures aborted after resuscitation with dextrose. There was no history of fever, exposure to insulin or other drugs, weight gain, family history of diabetes or alcohol use. CT brain and other parameters were normal and she had no other apparent cause of seizures. During the hypoglycemic episode; with the plasma glucose of 32 mg/dL, she had disproportionately high insulin: 9309 (3-25)mIU/L relative to C-peptide: 18.6 (0.9-7.1)ng/mL, with appropriate cortisol levels of 958 nmol/L. Sulphonylurea screen and pancreatic imaging was negative. Low insulin recovery was documented following PEG precipitation suggesting the presence of anti-insulin antibody. Elevated serum IAA levels at >20 (<2.4)U/mL with positive HLA-DRB1*04:06, confirmed the diagnosis of IAS. Multiple small, low carbohydrate and frequent meals were prescribed to prevent hypoglycemia and methimazole was discontinued as she had mild hyperthyroidism at this point (ft4 20.6 pmol/L, TSH <0.01mIU/L). Three days after discontinuation of methimazole, hypoglycemia completely resolved without need for dextrose infusion or corticosteroids. She received immediate 131-iodine therapy and developed hypothyroidism within two months, requiring levothyroxine replacement. She had not reported any hypoglycemia since and repeated IAA titre significantly diminished to 3.2 U/mL two months after discontinuation of methimazole. Conclusion: Methimazole-induced IAS is a rare cause of insulin mediated hypoglycemia, caused by cleaving of the disulphide bonds of insulin by the drug, leading to a cascade of autoimmune response in susceptible individuals. This is the first reported Malaysian case of methimazole- induced IAS. To date, this condition have almost always been reported in East- Asians in whom the DRB1*0406 genotype is relatively common. Unprovoked hypoglycaemia in a patient on anti-thyroid medications should prompt clinicians to consider methimazole-induced IAS. Presentation: 6/1/2024