title: Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease.
abstract: Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.
authors.affiliation: Department of Medical Genetics, Université Libre de Bruxelles, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Paschke
authors.forename: M
authors.initials: M
authors.lastname: Vogg
authors.forename: R
authors.initials: R
authors.lastname: Kristoferitsch
authors.forename: D
authors.initials: D
authors.lastname: Aktuna
authors.forename: O
authors.initials: O
authors.lastname: Wawschinek
authors.forename: O
authors.initials: O
authors.lastname: Eber
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D002231:Carbimazole / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008713:Methimazole / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013965:Thyroidectomy; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008713:Methimazole; D002231:Carbimazole