title: Serum thyroglobulin concentration as an indicator for assessing thyroid stimulation in patients with Graves' disease during antithyroid drug therapy.
abstract: OBJECTIVE
  The purpose of this study was to elucidate the mechanism of regulation of serum thyroglobulin concentration in patients with Graves' disease and to establish the clinical usefulness of this measurement.
  
  
  METHODS
  Serum thyroglobulin concentration was analyzed in relation to serum thyrotropin receptor antibody (TRab) titer and thyrotropin concentration in 166 patients with Graves' disease without thyroglobulin antibody.
  
  
  RESULTS
  A total of 113 patients were treated and had been kept euthyroid for at least 10 months with methimazole and underwent a triiodothyronine (T3) suppression test. At the time of the T3 suppression test, the serum thyroglobulin concentration (ng/mL) was 33 +/- 31 in 80 of them with T3-suppressible (radioiodine uptake less than 12%) thyroids, negative TRab titers (less than 15% displacement), and normal serum thyrotropin concentrations (0.1 to 3.0 mU/L). Patients with T3-non-suppressible thyroids were divided into three subgroups according to serum TRab titers and thyrotropin concentrations: those with a negative TRab titer and a normal serum thyrotropin concentration (n = 9), those with a positive TRab titer and a normal thyrotropin concentration (n = 18), and those with a positive TRab titer and undetectable thyrotropin (n = 6). Serum thyroglobulin concentrations (ng/mL) were 116 +/- 40 in the first group, 249 +/- 194 in the second group, and 399 +/- 205 in the third group. In the other 39 methimazole-treated patients, 72 determinations of serum thyroglobulin concentration were performed either before or during treatment without the T3 suppression test, and it correlated well with the TRab titer but not with the serum thyrotropin concentration. In 14 patients who became hypothyroid due to excess methimazole, the serum thyroglobulin concentration increased concurrently with elevation of the serum thyrotropin concentration and normalized during thyroxine supplementation. In treated patients with T3-suppressible thyroids, the serum thyroglobulin concentration was similar among those with positive (n = 54) and negative (n = 26) microsomal antibody, indicating that the presence of Hashimoto's thyroiditis does not profoundly affect the serum thyroglobulin level. Among 80 patients with T3-suppressible thyroids who were followed without methimazole for a mean period of 31.1 months, eight (10%) experienced a clinically overt recurrence of hyperthyroidism. Serum thyroglobulin concentration and TRab titer (%) in these eight patients were 188.1 +/- 101.7 and 27.8 +/- 12.6, respectively. Thyroglobulin and TRab did not increase in the patients who remained euthyroid (n = 71) or who experienced subclinical recurrence (n = 1).
  
  
  CONCLUSIONS
  Abnormal thyroid stimulator(s) and thyrotropin synergistically (if both are present in the serum) or independently (if either one is present) stimulate thyroglobulin secretion in patients with Graves' disease. Therefore, serum thyroglobulin concentration can be a useful means of assessing the degree of thyroidal stimulation and, if serum thyrotropin is normal or suppressed, correlates well with thyroidal stimulation even in patients with a negative TRab titer.
authors.affiliation: Department of Geriatrics, Endocrinology, and Metabolism, School of Medicine, Shinshu University, Nagano-ken, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aizawa
authors.forename: M
authors.initials: M
authors.lastname: Ishihara
authors.forename: Y
authors.initials: Y
authors.lastname: Koizumi
authors.forename: K
authors.initials: K
authors.lastname: Hashizume
authors.forename: N
authors.initials: N
authors.lastname: Takasu
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: Z
authors.initials: Z
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005500:Follow-Up Studies; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008713:Methimazole / Q000627:therapeutic use*; D008861:Microsomes / Q000276:immunology; D008875:Middle Aged; D017981:Receptors, Neurotransmitter / Q000276:immunology; D018025:Receptors, Thyrotropin-Releasing Hormone; D013954:Thyroglobulin / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D008713:Methimazole; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013954:Thyroglobulin