title: Hypothyroidism during antithyroid drug treatment with methimazole is a favorable prognostic indicator in patients with Graves' disease.
abstract: BACKGROUND
  A major problem with antithyroid drug (ATD) therapy in Graves' disease is the high relapse rate. Therefore, clinicians have sought prognostic indicators of permanent remission. Suppression of serum thyrotropin (TSH) when ATD therapy is stopped carries a poor prognosis, but little is known regarding the significance of elevated serum TSH concentrations in the course of ATD therapy. The objective of this study was to determine if elevated serum TSH concentrations during methimazole (MMI) therapy is associated with a favorable long-term prognosis.
  
  
  METHODS
  We retrospectively studied patients with Graves' disease who were initially on MMI, in whom this drug was stopped because they had undetectable thyroid-stimulating antibodies (TSAbs) or were euthyroid after at least 24 months on MMI treatment. A strategy of high MMI doses plus T4 was not used in these patients. We identified 40 patients with elevated serum TSH concentration (>10 microIU/mL) during MMI therapy (H-TSH group). Eighty-five percent of the H-TSH group had negative tests for TSAb. The H-TSH group was sex- and age-matched with 37 patients who had similar selection criteria, but did not have elevated serum TSH concentration during MMI therapy (N-TSH group). The H-TSH and N-TSH groups were similar in gross thyroid size, percentage of patients with exophthalmos, serum free thyroxine, duration of MMI treatment, TSAb status, duration that their TSAb tests remained negative, and thyroid peroxidase antibody titers. The patients were followed for 24 months after stopping MMI.
  
  
  RESULTS
  In the H-TSH group, MMI-associated hypothyroidism typically occurred after 7-8 months of treatment with daily doses of 10-15 mg MMI. No patient had severe symptoms of hypothyroidism. The percentage of patients in remission at 6, 12, and 24 months after discontinuation of MMI was 90.0, 87.5, and 85.0, respectively, in the H-TSH group and 70.3, 67.6, and 54.1, respectively, in the N-TSH group (p  <  0.05 for the comparison of groups at 6 and 12 months and p  <  0.001 for comparison of the groups at 24 months).
  
  
  CONCLUSIONS
  In patients with Graves' disease who are treated with MMI for at least 2 years and become euthyroid, the occurrence of elevated serum TSH concentrations during MMI treatment is a favorable indicator for long-term remission and is independent of multiple other factors including TSAb status, duration of MMI treatment, and gross parameters of goiter size.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Dankook University, Cheonan, Korea.
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Choo
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Yoo
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Chung
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D005094:Exophthalmos / Q000188:drug therapy; D005260:Female; D006042:Goiter / Q000188:drug therapy; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; C056626:thyroid microsomal antibodies; D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine