Blocking-type anti-TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves' disease.
OBJECTIVE
Antithyroid drugs are effective in some patients with Graves' disease but not in others. The factors responsible for this difference are still unknown. We examined the relationship between the nature of anti-TSH receptor (TSH-R) antibodies and responsiveness to drugs in Graves' disease.


METHODS
Twenty-eight untreated patients with Graves' disease were treated with thiamazole and followed for up to 13 years.


METHODS
Antithyroid microsomal antibodies (MCHAs) and antithyroglobulin antibodies (TGHAs) were measured by the passive haemagglutination method. Anti-TSH-R antibodies were measured by a radioreceptor assay (TBII), and thyroid-stimulating antibodies (TSAbs) and TSH-stimulation blocking antibodies (TSBAbs) were measured by bioassays using FRTL-5 cells. Blocking antibodies were also measured by the conversion assay. In order to confirm the usefulness of the conversion assay, in vitro experiments using mixtures of TSAb serum and TSBAb serum were performed.


RESULTS
In in vitro conversion experiments, the conversion assay sensitively detected coexisting blocking antibodies. TSBAb was found in seven patients and a positive conversion ratio was found in four patients, and, of these, three patients had both antibodies. Finally, eight patients (28.6%) had blocking antibodies and 25 of 28 patients (89.3%) had stimulating antibodies. These patients with blocking antibodies (Group A) responded well initially to antithyroid drugs and showed earlier normalization of the serum T4 level (3.0 +/- 1.2 weeks) than patients without blocking antibodies (Group B, 10.7 +/- 8.5, P < 0.001). Unexpectedly, remission of Graves' thyrotoxicosis was earlier in Group B (5.1 +/- 4.4 years) than in Group A (8.0 +/- 4.3 years, P < 0.05). Other parameters, including serum T4, goitre size, ophthalmopathy, TBII, TSAb, TGHA and MCHA, were not different between the two groups.


CONCLUSIONS
Graves' patients with coexisting blocking antibodies initially respond well to thiamazole but are relatively slow to achieve remission. Measurement of blocking antibodies may be useful for selection of treatment options in Graves' disease.
Tada
Hisato
H
Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Mizuta
Ikuko
I
Takano
Toru
T
Tatsumi
Ke-Ita
KI
Izumi
Yukiko
Y
Hidaka
Yoh
Y
Amino
Nobuyuki
N
D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008861:Microsomes / Q000276:immunology; D008875:Middle Aged; D018579:Patient Selection; D012074:Remission Induction; D018709:Statistics, Nonparametric; D013954:Thyroglobulin / Q000276:immunology; D013974:Thyroxine / Q000097:blood
D013956:Antithyroid Agents; D018828:Immunoglobulins, Thyroid-Stimulating; C118905:thyroid stimulation-blocking antibody; D008713:Methimazole; D013954:Thyroglobulin; D013974:Thyroxine