methimazole and Pancreatitis

Graves' disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves' hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI.. Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter.. This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.

Topics: Antithyroid Agents; Consensus; Female; Graves Disease; Humans; Hyperthyroidism; Italy; Methimazole; Pancreatitis; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

Topics: Acute Disease; Antithyroid Agents; Carbimazole; Drug Hypersensitivity; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancreatitis

The World Health Organization (WHO) has listed 525 different drugs, that can lead to acute pancreatitis cases, as a medication side-effect. Among them, methimazole (MMI also known as thiamazole, the active form of carbimazole [CBZ]) was included. We reported case reports of patients with overall features compatible with acute pancreatitis episodes following and presumably triggered by the exposure to MMI and its prodrug CBZ. A systematic search was performed on MEDLINE (PubMed). We included case reports of patients with overall features compatible with acute pancreatitis episodes following and presumably triggered by the exposure to MMI and its prodrug CBZ Data extraction and analysis were undertaken in duplicate. We identified 7 case reports. Most patients were female, and one patient was male. Mean age at baseline ranged from 18 to 80 years old. The average time, that elapses between the initiation of the therapy with MMI/CBZ and the onset of typical clinical signs and symptoms pathognomonic of acute pancreatitis, was 2-3 weeks. Based on the data derived from these case reports, it could be considered the possibility of a potential association between MMI/CBZ exposure. Evidence is, however, limited and requires more studies of high quality to confirm this association.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Carbimazole; Female; Humans; Male; Methimazole; Middle Aged; Pancreatitis; Prodrugs; Young Adult

Topics: Aged; Aged, 80 and over; Antithyroid Agents; Cardiovascular Diseases; Case-Control Studies; Cross-Over Studies; Diabetes Mellitus; Female; Gallstones; Graves Disease; Humans; Liver Diseases, Alcoholic; Male; Methimazole; Middle Aged; Pancreatitis; Prognosis; Risk Factors

Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Case-Control Studies; Comorbidity; Databases, Factual; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatitis; Pharmacovigilance; Propylthiouracil; Retrospective Studies; Risk; Taiwan; Thioamides

A warning has been recently issued by the European Medicine Agency (EMA) regarding a potential increased risk of acute pancreatitis (AP) in methimazole (MMI) users.. To investigate the association between MMI and the diagnosis of AP in a population-based study.. A retrospective analysis of administrative health databases was conducted (2013-2018). Relevant data were obtained from: (1) inhabitants registry, (2) hospital discharge records (ICD-9-CM 577.0), and (3) drug claims registry (ATC H03BB02). We evaluated AP risk in MMI users in 18 months of treatment, stratifying results by trimester. Poisson regression was used to estimate the age- and sex-adjusted rate ratios (RR), and the relative 95% confidence intervals (CI), comparing rates of AP between MMI users and nonusers. The absolute risk of AP in MMI users was also calculated.. A total of 23 087 new users of MMI were identified. Among them, 61 hospitalizations occurred during the study period. An increase in AP risk was evident during the first 3 trimesters of therapy (RR 3.40 [95% CI: 2.12-5.48]; RR 2.40 [95% CI: 1.36-4.23]; RR 2.80 [95% CI: 1.66-4.73]), but disappeared thereafter. The AP absolute risk in MMI users during the first 18 months of treatment was less than 0.4% in all sex and age classes.. Our results support the EMA warning, suggesting an increased risk of AP associated with MMI use. However, such an increase seems limited to the first months of MMI treatment. Moreover, in absolute terms, the probability of AP is low among patients, well below 1%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Cohort Studies; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Pancreatitis; Retrospective Studies; Risk Factors; Young Adult

Topics: Acute Disease; Antithyroid Agents; Cohort Studies; Humans; Methimazole; Pancreatitis

A 76-year-old Japanese woman was diagnosed with Graves' disease and was administered methimazole (MMI) 10 mg and potassium iodide 50 mg. After 19 days of the drug regime, she developed high-grade fever and nausea and was admitted to our hospital. Blood test results showed elevated pancreatic enzymes and C-reactive protein levels. Abdominal computed tomography showed swollen pancreas, and she was diagnosed with acute pancreatitis. These abnormalities improved after discontinuation of MMI. Five similar cases have been reported, but this is the first case report without abdominal pain. When acute pancreatitis is observed after the initiation of MMI, drug-induced pancreatitis should be considered as the possible etiology.

Topics: Aged; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Topics: Abdominal Pain; Acute Disease; Diagnosis, Differential; Fever of Unknown Origin; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancreatitis; Treatment Outcome

Antithyroid drugs such as methimazole (MMI), the mainstay of pharmacologic therapy for Graves' disease, can provoke a variety of adverse effects. MMI-induced acute pancreatitis is very rare, being described in only a few patients and never after more than two exposures as reported here. Here, we report an 18-year-old girl with Graves' disease who developed acute pancreatitis each time she received MMI.. The patient was an 18-year-old girl with Graves' disease who took MMI on four occasions. Each time she promptly developed similar features consisting of high fever and left upper quadrant abdominal pain. On three occasions, serum lipase and amylase values were measured. Serum lipase was elevated on all three occasions and serum amylase was elevated once. Features resolved after MMI was stopped. We considered these episodes to be most consistent with pancreatitis, and to be induced by MMI administration.. MMI-induced acute pancreatitis is rare and easily misdiagnosed. Based on very limited experience, it should resolve after MMI is stopped. The pathogenesis of MMI-induced pancreatitis is not known. Clinicians should be aware of this entity so that MMI is promptly stopped if the features described here develop after MMI is started, and measures are taken to avoid future MMI treatment.

Topics: Acute Disease; Adolescent; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis

Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats.. Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP.. Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05).. METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property.

Topics: Acute Disease; Amylases; Animals; Ceruletide; Disease Models, Animal; Hypothyroidism; Male; Methimazole; Pancreatitis; Rats; Rats, Wistar; Thyroid Hormones

A wide variety of adverse effects of methimazole (MMI) have been reported. Here we report a new MMI-induced disorder, acute pancreatitis and parotitis. Three weeks after a woman started MMI treatment for Graves' disease, she developed a high fever, painful parotid swelling and dull pain in the upper abdomen with elevation of the serum levels of salivary and pancreatic enzymes. These abnormalities disappeared soon after the withdrawal of MMI. However, the same abnormalities were rapidly provoked when MMI was reintroduced. Marked increases in the leucocyte count and CRP were also observed during these episodes. The possible mechanisms of MMI-induced pancreatitis/parotitis are discussed.

Topics: Acute Disease; Aged; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Pancreatitis; Parotitis