methimazole and Hypoglycemia

Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause harm to patients' cognition, consciousness, central nervous system, cardiovascular and cerebrovascular system, and even death. However, the most fundamental way to control hypoglycemia is to identify the cause and deal with the primary disease. This article introduces 3 cases of nondiabetic hypoglycemia with different causes, aiming to improve our understanding of nondiabetic hypoglycemia and improve the ability of early diagnosis and differential diagnosis.. Case 1 is a 19-year-old female with a history of recurrent coma, and magnetic resonance imaging and endoscopic ultrasound of the pancreas suggest insulinoma. Case 2 is a 74-year-old male with a history of viral hepatitis, and computerized tomography shows multiple nodules in the liver, which is diagnosed as liver cancer. Case 3 is a 39-year-old female with a history of taking methimazole, who tested positive for insulin antibodies, and was diagnosed with insulin autoimmune syndrome.. All 3 patients were diagnosed with nondiabetic hypoglycemia, but the causes varied, and included insulinoma, non-islet cell tumor-induced hypoglycemia, and insulin autoimmune syndrome.. Case 1 underwent pancreatic tail resection; case 2 refused anti-tumor treatment and received glucose injections for palliative treatment only; and case 3 stopped taking methimazole.. After surgery, the blood sugar in case 1 returned to normal, and the blood sugar in case 2 was maintained at about 6.0 mmol/L. The symptoms of hypoglycemia gradually improved in case 3 after stopping the medication.. Non-diabetic hypoglycemia requires further examination to clarify the cause, and the correct differential diagnosis can provide timely and effective treatment, improving the patient's prognosis.

Topics: Adult; Aged; Blood Glucose; Early Detection of Cancer; Female; Humans; Hypoglycemia; Insulin; Insulinoma; Male; Methimazole; Pancreatic Neoplasms; Young Adult

Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS.. The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia.. On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS.. The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months.. At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable.. We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS.

Topics: Abortion, Spontaneous; Adult; Autoimmune Diseases; Female; Follow-Up Studies; Gestational Age; Graves Disease; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Methimazole; Prednisone; Pregnancy; Pregnancy Complications; Rare Diseases; Risk Assessment; Syndrome

Topics: Adrenal Cortex Hormones; Antithyroid Agents; Autoimmune Diseases; Diet, Carbohydrate-Restricted; Genotype; Histocompatibility Testing; HLA Antigens; Humans; Hypoglycemia; Immunosuppressive Agents; Insulin; Insulin Antibodies; Methimazole; Sulfhydryl Compounds; Syndrome

Topics: Autoantibodies; Autoimmune Diseases; Diagnosis, Differential; HLA Antigens; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Insulin Antibodies; Methimazole; Syndrome; Tiopronin

Topics: Autoantibodies; Autoimmune Diseases; History, 20th Century; HLA Antigens; Humans; Hypoglycemia; Insulin Antibodies; Japan; Methimazole; Syndrome; Tiopronin

Topics: Autoantibodies; Diagnosis, Differential; HLA-DR Antigens; Humans; Hypoglycemia; Immunoglobulin G; Insulin; Methimazole; Prognosis; Syndrome

Topics: Autoantibodies; Autoimmune Diseases; HLA-DR Antigens; Humans; Hypoglycemia; Insulin; Japan; Methimazole

Topics: Adolescent; Adult; Clinical Trials as Topic; Female; Growth Hormone; Humans; Hydrocortisone; Hyperthyroidism; Hypoglycemia; Insulin; Male; Methimazole; Thyroidectomy

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of long-term follow-up of IAS in China is limited. We herein report a case of drug-induced IAS in a 44-year-old Chinese woman. She had been taking methimazole for Graves' disease and had subsequently presented with recurrent hypoglycemic episodes. Laboratory assessments on admission revealed that her serum insulin level was significantly elevated (>1000 µIU/mL) and that she was positive for serum insulin autoantibody, leading to a diagnosis of IAS. Human leukocyte antigen DNA typing identified *04:06/*09:01:02, an immunogenetic determinant associated with IAS. After treatment with prednisone for 2 months, the hypoglycemic episodes disappeared, her serum insulin level gradually declined, and her insulin antibody levels became negative. Clinicians should be aware of the potential for methimazole to trigger autoimmune hypoglycemia in people with a genetic predisposition.

Topics: Adult; Autoimmune Diseases; Female; Follow-Up Studies; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulin; Methimazole

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization.. We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge.. GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.

Topics: Autoantibodies; Autoimmune Diseases; Follow-Up Studies; Graves Disease; HLA-DRB1 Chains; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulins; Methimazole; Patient Discharge; Sulfhydryl Compounds

Hypoglycemia is an emergent condition with many causes, including underlying diabetes mellitus either with the use of insulin or oral anti-diabetic medications for glucose control, and organ (heart, hepatic, or renal) failure. Insulin autoimmune syndrome (IAS) can also cause hypoglycemia, however it is relatively difficult to diagnose as it is rare clinically. Although uncommon, IAS can be life threatening in patients with persistent hypoglycemia.. We report the case of a 27-year-old female with underlying Graves' disease who was treated with methimazole (MTZ). After 6 weeks of treatment, she developed hypoglycemia symptoms accompanied by dizziness and cold sweating. We excluded underlying diabetes mellitus, the use of insulin or oral anti-diabetic medications, and organ failure.. Laboratory data showed elevated insulin and C-peptide levels. Therefore, insulinoma and IAS were suspected. Abdominal computed tomography and magnetic resonance imaging ruled out insulinoma, and MTZ-induced IAS was finally diagnosed.. The hypoglycemia symptoms resolved after MTZ was switched to propylthiouracil, confirming the diagnosis of IAS.. This case emphasizes the significance of life-threatening MTZ-induced IAS. IAS should be suspected in patients who develop spontaneous hypoglycemia, especially in those with underlying Graves' disease receiving MTZ who present with hyperinsulinism.

Topics: Adult; Autoimmune Diseases; Diabetes Mellitus; Female; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulinoma; Methimazole; Pancreatic Neoplasms

Insulin autoimmune syndrome (IAS) is a rare endocrine disease characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals, elevated serum insulin, and positivity for insulin autoantibody (IAA) or insulin receptor antibody (IRA). We summarize the clinical manifestations and treatment experiences of 3 patients with IAS.. One patient with >20-year history of type 2 diabetes mellitus had irregular episodes of hypoglycemia 2 years of after treatment with insulin. Another patient with a 6-year history of type 2 diabetes mellitus presented irregular episodes of hypoglycemia after 6 months of treatment with insulin. One patient with a history of Graves' disease showed hypoglycemia after administration of thiamazole.. Serum islet cell antibody (ICA) and glutamic acid decarboxylase antibody (GADA) were negative, while antibody insulin autoantibodies were positive in all the 3 patients. Two patients demonstrated diabetes mellitus after an oral glucose tolerance test, while one had normal glucose tolerance. Furthermore, serum insulin levels significantly elevated and did not matched C peptide levels. No abnormalities were found on enhanced MRI of the pancreas, and all 3 patients were clinically diagnosed with IAS.. In case one, insulin aspart 30 injection was withdrawn after admission. In addition, the patient was prescribed sublingual acarbose 3 times daily. Two weeks after admission, prednisone acetate was administered orally once daily at night. In case 2, insulin aspart 30 injection was withdrawn after admission, the patient was prescribed sublingual acarbose 3 times daily with a meal. Five days after admission, oral prednisone acetate was administered once daily at night. In case 3, oral propylthiouracil was prescribed and thiamazole withdrawn after admission, and the patient consumed an extra meal before sleeping.. At the 3-month follow-up visit, the hypoglycemic episodes had disappeared, serum insulin levels were significantly decreased, and insulin antibody (IA) levels were no longer detectable in all 3 patients.. For those patients with high-insulin hypoglycemia, IAA should be evaluated if serum insulin concentrations are inconsistent with C peptide levels. Therapeutically, a lower dose of glucocorticoids with more appropriate medication timing can be used to achieve good results.

Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Methimazole; Middle Aged; Syndrome

The older of a pair of sisters experienced hypoglycemia after the start of thiamazole (MMI) treatment. Based on a high insulin antibody level, she was diagnosed with insulin autoimmune syndrome (IAS). HLA-DNA typing identified DRB1*04:06. Although a 75-g oral glucose tolerance test (OGTT) showed biphasic insulin secretion, the secretion pattern became monophasic after discontinuation of the MMI. The younger sister was diagnosed with IAS after the start of MMI treatment. HLA-DNA typing identified DRB1*04:06. The 75-g OGTT showed biphasic insulin secretion, but it became monophasic after discontinuation of the MMI. According to the similar insulin secretion kinetics in the two sisters with IAS, we suspect that a genetic predisposition may be associated with the features of anti-insulin antibodies.

Topics: Adult; Antithyroid Agents; Autoimmune Diseases; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Graves Disease; HLA-DRB1 Chains; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Antibodies; Insulin Secretion; Methimazole; Siblings

Topics: Aged, 80 and over; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hypoglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Insulin, Regular, Human; Methimazole; Prednisone; Recombinant Proteins; Treatment Outcome

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African-American adolescent. A 16-yr-old healthy African-American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio-ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia.

Topics: Adolescent; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Black or African American; Diazoxide; Graves Disease; Humans; Hypoglycemia; Insulin; Male; Methimazole; Prednisone; Propranolol

Although insulin autoimmune syndrome (IAS) was found to be strongly related with methimazole, rapidly increasing numbers of cases with alpha lipoic acid-induced IAS have been confirmed to be reported since 2003. As alpha lipoic acid has gained popularity as a supplement for dieting and anti-aging, a warning should be issued.

Topics: Autoimmune Diseases; Dietary Supplements; Humans; Hypoglycemia; Insulin; Methimazole; Thioctic Acid

The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacerbated IAS in the present case, although his HLA combination is identical to that of the previous cases.

Topics: Adult; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Follow-Up Studies; Graves Disease; Histocompatibility Testing; Humans; Hyperthyroidism; Hypoglycemia; Insulin; Male; Methimazole; Syndrome; Thyroid Hormones

In 1986, a 26-year-old female had been diagnosed as having Graves' disease and had been treated with methimazole for four months. After the treatment with propylthiouracil for another four months, she had been treated with methimazole once again. She was in complete remission for two years. She again experienced symptoms of hyperthyroidism, and treatment with methimazole was started again. On the thirteenth day after treatment, she experienced hypoglycemic attacks with skin eruption. The plasma glucose was 57 mg/dl, 125I-Insulin binding 69%, free IRI 196 microU/ml. The patient had the HLA-DRB1*0406.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Female; Graves Disease; Humans; Hyperinsulinism; Hypoglycemia; Insulin Antibodies; Methimazole

Insulin autoimmune syndrome is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients who have never been exposed to exogenous insulin. Four cases who developed symptoms of hypoglycemic attack with self-limited duration and spontaneous remission were collected in our hospital from 1984 to 1988. The elevated serum total and free insulin and C-peptide levels, as well as the titer of insulin autoantibodies, decreased gradually; but insulin autoantibodies were still present in the serum for more than six months after the initial episodes of hypoglycemia. Three of four patients had Graves' disease and developed the syndrome after methimazole treatment. The fourth one had a history of hemorrhagic cystitis and denied history of specific drug exposure. The cause or stimulus for insulin autoantibody formation is still unknown, but drugs containing a sulfhydryl group like methimazole may play a role in the development of the syndrome. Extremely high insulin antibodies in patients with fasting hypoglycemia along with elevated serum levels of insulin and C-peptide suggest a diagnosis of insulin autoimmune syndrome and usually exclude the possibility of insulinoma or factitious hypoglycemia.

Topics: Adult; Aged; Autoimmune Diseases; C-Peptide; Female; Humans; Hypoglycemia; Insulin Antibodies; Methimazole

Topics: Aged; Autoimmune Diseases; Female; Humans; Hyperthyroidism; Hypoglycemia; Insulin Antibodies; Methimazole

Topics: Adult; Autoantibodies; Autoimmune Diseases; Carbimazole; Cross-Sectional Studies; Female; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Male; Methimazole; Syndrome; Taiwan

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, glucose intolerance, hyperinsulinemia and insulin-binding antibodies in serum without previous immunization. A 31-year-old man with Graves' disease developed insulin autoantibodies after therapy with methimazole. The patient was unique in that persistent hyperglycemia with polyuria and polydipsia had continued for several days before frequent hypoglycemic attacks appeared. We were able to extract a huge amount of immunoreactive insulin (116,000 microU/ml) with acid-ethanol from his serum obtained in the diabetic stage, and serum C-peptide immunoreactivity was as high as 268 ng/ml. The insulin-binding activity of his serum was quite potent, and when 1:5,000 diluted serum was incubated with 125I-porcine insulin, 71.2% of the label could be precipitated by polyethylene glycol. The insulin-binding protein was identified as mainly IgG with kappa light chains. Insulin-binding activity was not detected in serum obtained before methimazole therapy, suggesting that the drug was responsible for the induction of antibodies in this patient. The antibodies recognized porcine, sheep, bovine and horse insulins as well as human insulin. The mechanisms by which the antibodies produced hyper- and hypoglycemia have also been discussed.

Topics: Adult; Autoantibodies; Glucose Tolerance Test; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Insulin Resistance; Male; Methimazole

"Autoimmune" hypoglycemia is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia, and insulin-binding antibodies in a patient who has never been exposed to exogenous insulin. The stimulus for insulin-antibody formation and the mechanism of the hypoglycemia in this condition remain unknown. Three patients with this rare syndrome had severe hypoglycemia of limited duration. Two had received a drug containing a sulfhydryl group (methimazole and penicillamine) as treatment for an autoimmune disorder (Graves' disease and rheumatoid arthritis, respectively). A third patient who underwent surgery for a suspected insulinoma was found to have pancreatic beta cell hyperplasia. Drugs containing a sulfhydryl group may have a role in the etiology of the syndrome. Additionally, our findings suggest a relationship between circulating insulin antibodies and beta cell hyperplasia.

Topics: Autoantibodies; Diagnosis, Differential; Female; Humans; Hyperplasia; Hypoglycemia; Insulin Antibodies; Insulinoma; Islets of Langerhans; Male; Methimazole; Middle Aged; Pancreatic Neoplasms; Penicillamine; Syndrome

Topics: Autoimmune Diseases; Graves Disease; Humans; Hypoglycemia; Insulin Antibodies; Methimazole; Syndrome

Topics: Autoimmune Diseases; Humans; Hypoglycemia; Insulin Antibodies; Methimazole; Syndrome

Topics: Adult; Antigens; Autoantibodies; Binding Sites, Antibody; Blood Glucose; Female; Glucose Tolerance Test; Graves Disease; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Iodine Radioisotopes; Methimazole; Protein Binding; Radioimmunoassay