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PubMed1996

Effect of methimazole treatment of maternal thyrotoxicosis on thyroid function in breast-feeding infants.

In 35 infants of lactating mothers with thyrotoxicosis who were receiving 5 to 20 mg methimazole daily, serum levels of thyroxine, triiodothyronine, thyrotropin were within normal ranges 1 month after the start of breast-feeding. Thyroid function in breast-feeding infants of six lactating mothers receiving methimazole, 20 mg for the first, 10 mg for the second, and 5 mg for an additional 4 months, remained normal. These results suggest the safety of methimazole therapy in lactating mothers.

Adult↗
PubMed1980

Determination of methimazole in plasma using gas chromatography--mass spectrometry after extractive alkylation.

A gas chromatography--mass spectrometry method for quantitation of the thyreostatic agent methimazole in plasma is described. The drug was transferred from the plasma sample and derivatized in one step by extractive alkylation. Either of two alkylating agents benzyl-chloride or pentafluorobenzyl bromide were used. Deuterium-labelled methimazole was used as internal standard. The precision of the method at the level of 5 ng methimazole per ml plasma was 6%.

Alkylation↗
PubMed2003

Potentiometric and voltammetric determination of methimazole.

The determination of methimazole was investigated by potentiometric titration in an alkaline medium involving its reaction with iodine and square wave voltammetry (SWV) in 0.1 mol/l Tris-HCl buffer at pH 7.2. In potentiometric titration, the range of determination was 10-500 micromol. A stoichiometric reaction was obtained within the concentration range 0.75-1.25 mol/l of sodium hydroxide by potentiometric titration. A linear calibration graph was obtained over the concentration range 1-700 micromol/l by SWV. The lowest concentration of methimazole detected was 0.5 micromol/l. The relative standard deviations (R.S.D.) were 0.81% in potentiometric titration and 2.89% in square wave voltammetric analysis of thyromazol tablets. The data showed that potentiometric titration using iodine in sodium hydroxide can be used for the determination of methimazole in drug samples without prior separation.

Electrochemistry↗
PubMed1988

Improvement of immunologic abnormalities associated with hyperthyroidism of Graves' disease during methimazole treatment.

In an attempt to study the effects of methimazole treatment on immunologic abnormality of hyperthyroidism of Graves' disease, TSH receptor antibody (TRab), anti-DNA antibody and HLA-DR were measured in untreated patients with hyperthyroidism of Graves' disease and treated patients with methimazole for 2 years, using peripheral blood. In untreated patients, all 3 parameters elevated above normal. Three parameters decreased 2 years after methimazole treatment, but the magnitude of decrease was more in T3-suppressible patients than in T3-unsuppressible patients. However, both anti-DNA antibody and HLA-DR were significantly more in T3-suppressible patients than in normal subjects. It is suggested that immunologic abnormalities should largely be improved before remission of Graves' disease can be obtained.

Adolescent↗
PubMedDate not supplied

Methimazole-induced damage in the olfactory mucosa: effects on ultrastructure and glutathione levels.

Methimazole is an antithyroid drug that can induce loss of smell and taste in humans. It is also an olfactory toxicant in rodents. The aim of the present study was to examine involvement of glutathione in methimazole-induced damage of the olfactory mucosa (OM) of mice, and to study early onset of this damage using transmission electron microscopy (TEM). We found that an intraperitoneal dose of methimazole induced a dose-dependent decrease of nonprotein sulfhydryl groups (NP-SH; mainly glutathione) in the OM. Hepatic NP-SH was not decreased. One hour after administration (50 mg/kg), TEM demonstrated an extensive damage to acinar and intraepithelial excretory duct cells of Bowman's glands (BG) including dilatation of the endoplasmic reticulum and mitochondrial swelling. Furthermore, large vacuoles were noted in basal intraepithelial duct cells. After 2 hours there were ruptures of secretory granule membranes in BG and mitochondrial swelling and degeneration of sustentacular cells. The basal cells were less damaged. After four hours the neuroepithelium was disorganized although the columnar organization of neurons was largely intact. The acinar organization of the BG was frequently lost. The subsequent detachment of the neuroepithelium is suggested to be secondary to extensive damage of BG excretory ducts and sustentacular cells.

Animals↗
PubMed2006

Cholestasis secondary to hyperthyroidism made worse by methimazole.

A 28-year-old man presented with weight loss, jaundice, and pruritus. This was diagnosed to be secondary to Graves disease and the patient was prescribed methimazole. He returned 2 weeks later with worsening of his jaundice. Further investigation, including liver biopsy, indicated that there was superimposed methimazole-induced cholestasis. Discontinuation of methimazole and treatment of hyperthyroidism with lithium followed by radioactive iodine therapy resulted in resolution of his symptoms. This case highlights the fact that worsening cholestasis after therapy for Graves disease should raise the possibility of thionamide-induced exaggeration of liver cholestasis.

Adult↗
PubMed1976

Agranulocytosis secondary to methimazole therapy: report of two cases.

Seventy-three cases of thyrotoxicosis were treated at Lloyd Noland Hospital with methimazole, propylthiouracil or both. Two cases of agranulocytosis occurred (2.7%) secondary to methimazole. Both responded to hospitalization, reverse isolation, and antibiotic coverage with complete recovery of the peripheral blood picture. The toxicity of methimazole is noted. The need for careful monitoring of blood counts during therapy and immediate discontinuance of the drug at the first clinical sign of granulocytopenia is stressed.

Adult↗
PubMed1980

The pharmacokinetics of methimazole in pregnant patients after oral administration of carbimazole.

1 A high performance liquid chromatographic (HPLC) method was used to study the pharmacokinetics of methimazole after oral administration of carbimazole to women in various stages of pregnancy. 2 In one patient it was possible to conduct the study in the first and third timesters: there was an appreciable increase in the apparent clearance of methimazole. 3 Based on the assumption of complete absorption and hydrolysis of carbimazole to methimazole the mean apparent clearance was found to be significantly higher in pregnant patients receiving 10 mg carbimazole than in non-pregnant patients receiving the same dose.

Administration, Oral↗
PubMed1995

ANCA-associated vasculitis and lupus-like syndrome caused by methimazole.

A 24-year-old woman with Graves' disease treated with methimazole for 4 years, developed recalcitrant ulcers on the lower legs. Histological studies demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition. Laboratory investigation revealed lupus-like abnormalities (leucocytopenia, positive antinuclear and antidouble strand (ds) DNA antibodies, and positive ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In addition, leucocytopenia and the immunological abnormalities soon faded. Although lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis is a rare complication. To the best of our knowledge, this is the first report describing ANCA-associated vasculitis caused by methimazole.

Adult↗
PubMed1979

Rapid conversion of carbimazole to methimazole in serum; evidence for an enzymatic mechanism.

Carbimazole (CBZ) is one of the major drugs currently used for the treatment of Graves' disease. It is a carbethoxy derivative of methimazole (MMI), originally developed in the hope of obtaining a longer acting drug than methimazole. In the present study we have demonstrated that carbimazole is rapidly converted to methimazole in vitro by serum from rats and humans, and we have obtained evidence that this conversion is enzymatic. Experiments with [35S] CBZ in rats showed that the drug is so rapidly transformed to MMI after i.v. injection (within 3 min) that very little of the unchanged drug would be expected to reach the thyroid gland. The antithyroid action of CBZ in rats, therefore, can be ascribed entirely to the MMI to which it is rapidly converted. Although no experiments were performed with human subjects in vivo, the very rapid conversion of CBZ to MMI by human serum in vitro suggests that the antithyroid action of CBZ in humans can also be attributed to MMI. The original expectation of a longer acting drug has, therefore, not been met by CBZ. On the basis of the studies reported here there appears to be no advantage in using CBZ in preference to MMI for the treatment of Graves' disease. Although the in vivo action of CBZ must be attributed to its rapid conversion to MMI, the drug does possess inherent antithyroid activity. This was shown in the present study by the finding that CBZ is as potent as MMI in blocking thyroid peroxidase-catalysed iodination of thyroglobulin.

Animals↗
PubMed1986

The immunosuppressive effect of methimazole on cell-mediated immunity is mediated by its capacity to inhibit peroxidase and to scavenge free oxygen radicals.

We have investigated the effect of methimazole (MMI) on cell-mediated immunity and ascertained the mechanisms of immunosuppression produced by the drug. Methimazole (greater than or equal to 10(-5) M) produced a dose-dependent inhibition in 'active' (early) rosette formation with sheep red cells and in phytohaemagglutinin (PHA)-induced lymphocyte transformation. A concentration of 10(-4) M MMI inhibited the immediate rise in intracellular cAMP triggered by PHA and the subsequent time dependent decrement over 24 h. The drug (10(-3) M) also exerted a significant inhibitory effect on antibody-dependent cell-mediated cytotoxicity (ADCC) over six-fold difference in target/effector cell ratios. At a concentration of 10(-5) M, MMI inhibited zymosan-induced respiratory burst (determined by change in the chemiluminescence of oxidized luminol) in polymorphonuclear and mononuclear cell preparations. Ninety-five per cent of the chemiluminescence in the latter preparation was due to monocytes. At concentrations between 10(-7) and 10(-6) M, MMI significantly inhibited (in cell-free systems) horseradish peroxidase-dependent generation of chemiluminescence as well as the oxidation of luminol by hydrogen peroxide. Methimazole exerts its inhibitory effects on measures of cell-mediated immunity by at least two mechanisms: inhibition of peroxidase and scavenging free oxygen radicals. Insensitivity of the test systems or poor access of MMI to leucocytes may account for the need for greater than or equal to 10(-5) M MMI to inhibit cell-mediated immunity significantly.

Animals↗
PubMed1988

Methimazole-induced agranulocytosis: growth inhibition of myeloid progenitor cells by the patient's serum.

The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Adult↗
PubMed1996

Influence of rearing temperature on lung development following methimazole treatment of postnatal lambs.

This study examines the effect of ambient temperature on lung development over the first month of postnatal life in lambs treated with a drug which inhibits thyroid hormone synthesis (methimazole, 50 mg day-1 (kg body wt-1)). Twin lambs were hand-reared at a fixed level of nutrition in either a warm (WR, 25 degrees C) or cool (CR, 10-15 degrees C) ambient temperature. Plasma thyroid hormone concentrations were significantly (P < 0.05) lower in WR lambs, but there were no differences between WR and CR groups in thyroid gland weight or hepatic iodothyronine 5'-deiodinase activity at 8 or 29 days of age. Lung weights and the ratio of lung weight to O2 consumption were similar in WR and CR groups at 8 days but both were significantly lower (P < 0.01) in CR lambs at 29 days. Lung weight at 29 days was significantly (P = 0.002) correlated with plasma triiodothyronine concentration in CR but not WR lambs, and laryngeal braking of expiratory airflow was observed in three of seven CR lambs but not in WR lambs. Four WR, but no CR, lambs exhibited a rapid deterioration in health or died unexpectedly between 14 and 21 days of age. These WR lambs were characterized by having small lungs and slower growth rates. It is concluded that in WR lambs chronically treated with methimazole, both lung development and the ability of an individual to adapt effectively to methimazole treatment are compromised. In CR lambs, although lung growth may be reduced this does not appear to compromise O2 consumption or health.

Animals↗
PubMed1988

Co-oxidation of arachidonic acid and methimazole by prostaglandin endoperoxide synthetase.

The thiocarbamide methimazole stimulated O2 utilisation when added to reaction mixtures containing ram seminal vesicle microsomes (prostaglandin endoperoxide synthetase preparation) and arachidonic acid. This stimulation increased with increasing methimazole concentrations, as did the production of prostaglandin E. 2-[14C]Methimazole was co-oxidized to 1-methyl-2-[14C]imidazole.

Animals↗
PubMed1989

Effects of methimazole on the 5'-monodeiodinase activities of various tissues.

Iodothyronine 5'-deiodinases were assayed in preparations of liver, cerebral cortex and brown adipose tissue. Rate profiles at various pH values revealed that methimazole activates the liver enzyme (type I) and inhibits the enzyme from brown adipose tissue (type II). Other results show that the type II enzyme may be activated by methimazole when the concentration of endogenous sulfhydryl cofactor or of dithiothreitol in the system is low. Collectively, these results suggest an interplay between the sulfhydryl (-SH) tautomer of methimazole and the sulfhydryl activators of the enzymes.

Adipose Tissue, Brown↗
PubMed1982

Methimazole: an alternative route of administration.

Methimazole was administered orally and rectally in a single dose of 60 mg to six euthyroid volunteers (three females and three males). Blood levels of methimazole were the same whether administered by the oral or rectal route, with peak levels of 1184 +/- 118 and 1163 +/- 150 (+/-SEM) ng/ml respectively. This study provides evidence that the rectal administration of methimazole may be an alternative to treating hyperthyroid patients who are unable to take this drug by mouth.

Absorption↗
PubMed1999

Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves' hyperthyroidism.

Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.

Adult↗
PubMed2001

The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study.

The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.

Adult↗