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The Journal of Clinical Investigation Jan 1973Thyroxine (T(4)) and triiodothyronine (T(9)) are rapidly degraded by a purified preparation of myeloperoxidase (MPO) and H(2)O(2) with the formation of iodide and...
Thyroxine (T(4)) and triiodothyronine (T(9)) are rapidly degraded by a purified preparation of myeloperoxidase (MPO) and H(2)O(2) with the formation of iodide and material which remains at the origin on paper chromatography. Deiodination by MPO and H(2)O(2) occurs more readily at pH 7.0 than at pH 5.0 in contrast to iodination by this system which is known to occur more readily at pH 5.0 than at pH 7.0. Degradation is inhibited by azide, cyanide, ascorbic acid, and propylthiouracil. Methimazole stimulates deiodination by MPO and H(2)O(2) but inhibits this reaction when MPO is replaced by lactoperoxidase or horseradish peroxidase.Intact human leukocytes, in the resting state, degrade T(4) and T(3) slowly: degradation, however, is increased markedly during phagocytosis of preopsonized particles. Serum inhibits this reaction. T(3) can be detected as a minor product of T(4) degradation. Proteolytic digestion of the reaction products increases the recovery of monoiodotyrosine. The fixation of iodine in the cytoplasm of leukocytes which contain ingested bacteria was detected radioautographically. Chronic granulomatous disease leukocytes, which are deficient in H(2)O(2) formation, degrade T(4) and T(3) poorly during phagocytosis. MPO-deficient leukocytes degrade the thyroid hormones at a slower rate than do normal leukocytes although considerable degradation is still observed. Azide, cyanide, ascorbic acid, and propylthiouracil which inhibit certain peroxidasecatalyzed reactions inhibit degradation by normal leukocytes; however, inhibition is incomplete. Formation of iodinated origin material is inhibited to a greater degree by azide, cyanide, and propylthiouracil than is deiodination. Methimazole inhibits the formation of iodinated origin material by both normal and MPO-deficient leukocytes. However, deiodination by normal leukocytes is stimulated and that of MPO-deficient leukocytes is unaffected by methimazole. Hypoxia inhibits the degradation of T(4) and T(3) by untreated normal or MPO-deficient leukocytes and by normal leukocytes treated with azide or methimazole. These data suggest that both MPO-dependent and MPO-independent systems are involved in the degradation of T(4) and T(3) by phagocytosing leukocytes. The role of leukocytic degradation of T(4) and T(3) in thyroid hormone economy and in leukocytic microbicidal activity is considered.
Topics: Ascorbic Acid; Azides; Chromatography, Gel; Chromatography, Paper; Cyanides; Electrophoresis, Paper; Humans; Hydrogen Peroxide; In Vitro Techniques; Iodine Isotopes; Lactobacillus acidophilus; Leukocytes; Metabolism, Inborn Errors; Methimazole; Oxygen; Peroxidases; Phagocyte Bactericidal Dysfunction; Phagocytosis; Propylthiouracil; Thyroid Hormones; Thyroxine; Triiodothyronine
PubMed: 4629909
DOI: 10.1172/JCI107174 -
Journal of the American Veterinary... Apr 2003To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism.
DESIGN
Randomized, nonblinded, clinical trial.
ANIMALS
40 cats with newly diagnosed hyperthyroidism.
PROCEDURE
Cats were randomly assigned to receive 5 mg of methimazole, PO, once daily (n = 25) or 2.5 mg of methimazole, PO, twice daily (15). A complete physical examination, including measurement of body weight; CBC; serum biochemical analyses, including measurement of serum thyroxine concentration; and urinalysis were performed, and blood pressure was measured before and 2 and 4 weeks after initiation of treatment.
RESULTS
Serum thyroxine concentration was significantly higher in cats given methimazole once daily, compared with cats given methimazole twice daily, 2 weeks (3.7 vs 2.0 micro +/- g/dL) and 4 weeks (3.2 vs 1.7 microg/dL) after initiation of treatment. In addition, the proportion of cats that were euthyroid after 2 weeks of treatment was lower for cats receiving methimazole once daily (54%) than for cats receiving methimazole twice daily (87%). Percentages of cats with adverse effects (primarily gastrointestinal tract upset and facial pruritus) were not significantly different between groups.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggest that once daily administration of methimazole was not as effective as twice daily administration in cats with hyperthyroidism and cannot be recommended for routine use.
Topics: Administration, Oral; Animals; Antithyroid Agents; Cat Diseases; Cats; Drug Administration Schedule; Hyperthyroidism; Methimazole; Safety; Thyroxine; Treatment Outcome
PubMed: 12685785
DOI: 10.2460/javma.2003.222.954 -
BMC Endocrine Disorders Jan 2023Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction....
BACKGROUND
Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome.
CASE PRESENTATION
A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later.
CONCLUSIONS
Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.
Topics: Female; Humans; Adult; Drug Hypersensitivity Syndrome; Propylthiouracil; Methimazole; Eosinophilia; Exanthema; Hyperthyroidism
PubMed: 36691013
DOI: 10.1186/s12902-023-01273-x -
Journal of Veterinary Internal Medicine 2009Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours...
BACKGROUND
Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours after administration of methimazole and optimal time for blood sampling to monitor therapeutic efficacy have not been determined.
OBJECTIVE
To assess thyroid hormone concentration variation in serum of normal and hyperthyroid cats after administration of methimazole.
ANIMALS
Four healthy cats and 889 retrospectively acquired feline thyroid hormone profiles.
METHODS
Crossover and retrospective studies. In the crossover study, healthy cats were treated with increasing doses of oral methimazole until steady state of thyroid suppression was achieved. Thyroid hormones and thyroid stimulating hormone (TSH) were serially and randomly monitored after methimazole. Paired t-tests and a 3-factor analysis of variance were used to determine differences between thyroid hormone concentrations in treated and untreated cats in the crossover study. Thyroid profiles from methimazole-treated hyperthyroid cats were retrieved from the Diagnostic Center for Population and Animal Health database and reviewed. Linear regression analysis evaluated relationships of dosage (mg/kg), dosing interval (q24h versus q12h), and time after methimazole to all thyroid hormone concentrations.
RESULTS
All serum concentrations of thyroid hormones were significantly suppressed and TSH was significantly increased for 24 hours after administration of oral methimazole in healthy cats (P < .005). In hyperthyroid cats, there were no significant relationships between thyroid hormone concentrations and time postpill or dosing interval.
CONCLUSIONS
Timing of blood sampling after oral methimazole administration does not appear to be a significant factor when assessing response to methimazole treatment.
Topics: Animals; Antithyroid Agents; Cat Diseases; Cats; Cross-Over Studies; Female; Hyperthyroidism; Linear Models; Methimazole; Retrospective Studies; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine
PubMed: 19678886
DOI: 10.1111/j.1939-1676.2009.0370.x -
Journal of Veterinary Internal Medicine 2004The objective of this study was to determine whether transdermal methimazole was as safe and effective as oral methimazole for the control of hyperthyroidism in cats....
The objective of this study was to determine whether transdermal methimazole was as safe and effective as oral methimazole for the control of hyperthyroidism in cats. Forty-seven cats with newly diagnosed hyperthyroidism were randomized to receive either transdermal methimazole in pluronic lecithin organogel (PLO; applied to the inner pinna), or oral methimazole (2.5 mg q12h for either route). Cats were evaluated at weeks 0, 2, and 4 with a physical exam, body weight determination, CBC, biochemical panel, urinalysis, measurement of total levothyroxine (T4) concentration, indirect Doppler blood pressure determinaiton, and completion of an owner questionnaire. Data between the 2 groups and over time were compared by nonparametric methods. Forty-four cats followed the protocol (17 oral and 27 transdermal). Significantly more cats treated with oral methimazole had serum T4 concentrations within the reference range after 2 weeks (14 of 16 cats) compared to those treated by the transdermal route (14 of 25; P = .027). This difference was no longer significant by 4 weeks of treatment (9 of 11 for oral versus 14 of 21 for transdermal), possibly because of inadequate numbers evaluated by 4 weeks. Cats treated with oral methimazole had a higher incidence of gastrointestinal (GI) adverse effects (4 of 17 cats) compared to the cats treated with transdermal methimazole (1 of 27; P = .04), but no differences were found between groups in the incidence of neutropenia, hepatotoxicity, or facial excoriations. Although the overall efficacy of transdermal methimazole is not as high as that of oral methimazole at 2 weeks of treatment, it is associated with fewer GI adverse effects compared to the oral route.
Topics: Administration, Cutaneous; Administration, Oral; Animals; Antithyroid Agents; Cat Diseases; Cats; Gels; Hyperthyroidism; Methimazole; Radioimmunoassay; Reaction Time; Safety; Treatment Outcome
PubMed: 15515580
DOI: 10.1892/0891-6640(2004)18<651:easotm>2.0.co;2 -
Canadian Family Physician Medecin de... Aug 2009I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close...
QUESTION
I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close to delivery and might require antithyroid therapy in the postpartum period. Can methimazole cross into human milk, and is breastfeeding safe for her infant?
ANSWER
The exposure of infants to methimazole or propylthiouracil through breast milk is minimal and not clinically significant. Women with hyperthyroidism using methimazole or propylthiouracil should not be discouraged from breastfeeding, as the benefits of breastfeeding largely outweigh the theoretical minimal risks.
Topics: Antithyroid Agents; Breast Feeding; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Infant; Infant, Newborn; Lactation; Maternal Exposure; Methimazole; Milk, Human; Pregnancy; Propylthiouracil; Thyroid Gland; Treatment Outcome
PubMed: 19675263
DOI: No ID Found -
Brazilian Journal of Otorhinolaryngology 2019The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating...
INTRODUCTION
The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations.
OBJECTIVE
To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole.
METHODS
This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n=36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n=33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n=13).
RESULTS
ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis.
CONCLUSION
This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.
Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Brazil; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Prospective Studies
PubMed: 30057255
DOI: 10.1016/j.bjorl.2018.05.014 -
PloS One 2012The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to...
The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain.
Topics: Animals; Axons; Memory; Methimazole; Mice; Neurons; Odorants; Olfactory Bulb
PubMed: 23071557
DOI: 10.1371/journal.pone.0046338 -
BMJ Case Reports May 2015A 29-year-old pregnant woman with Graves' disease presented with severe persistent hypocalcaemia after thyroidectomy. Six months prior to presentation she was diagnosed... (Review)
Review
A 29-year-old pregnant woman with Graves' disease presented with severe persistent hypocalcaemia after thyroidectomy. Six months prior to presentation she was diagnosed with Graves' disease and remained uncontrolled with methimazole. She was confirmed pregnant prior to radioactive iodine ablation (RAI), and underwent total thyroidectomy during her second trimester. After surgery, continuous intravenous calcium infusion was required until delivery of the fetus allowed discontinuation at postoperative day 18, despite oral calcium and calcitriol administration. A total of 38 g of oral and 7.5 g of intravenous elemental calcium was administered. We report an unusual case of recalcitrant hypocalcaemia thought to be due to a combination of postoperative hypoparathyroidism, combined with thyrotoxic osteodystrophy and pregnancy, after surgical correction of Graves' disease. Increased vigilance and early calcium supplementation should be a priority in the management of these patients.
Topics: Administration, Oral; Adult; Antithyroid Agents; Calcium; Drug Administration Schedule; Female; Graves Disease; Humans; Hypocalcemia; Hypoparathyroidism; Infusions, Intravenous; Methimazole; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Thyroidectomy; Thyrotoxicosis; Time Factors; Treatment Outcome
PubMed: 25969482
DOI: 10.1136/bcr-2014-206967 -
Journal of Korean Medical Science Jul 2012Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of...
Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.
Topics: Adult; Anti-Inflammatory Agents; Antirheumatic Agents; Antithyroid Agents; Blister; Drug Therapy, Combination; Female; Graves Disease; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Methimazole; Mycophenolic Acid; Prednisolone; Skin
PubMed: 22787382
DOI: 10.3346/jkms.2012.27.7.818