Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.
OBJECTIVE
After primary successful antithyroid drug treatment (ATDT), Graves' disease has a relapse rate of 30% to 50%. Previous studies have evaluated age, gender, goiter volume, smoking habits, and the presence of thyrotropin-receptor antibodies (TRAb) as predictive markers to facilitate an individualized patient management. Despite higher sensitivity and specificity of the new second generation human TSH-receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of Graves' disease. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism.


METHODS
Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third-generation TSH assay and a second-generation recombinant TSH receptor assay. Relapse of Graves' disease was evaluated for a total follow-up of 2 years.


RESULTS
Within 2 years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first 4 weeks after withdrawal of ATDT and were thus considered to have persistent Graves' disease. Ten of 15 other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism relapsed within 2 years. Twenty-five of 65 patients with normal TSH (0.3-3.0 mU/L) and 3 of 4 patients with TSH values above 3 mU/L also had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of Graves 'disease. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L +/- 0.17) than TRAb values in the remission group (4.5 IU/L +/- 0.6), p < 0.001. Using a cutoff value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity, 14%), but with a cutoff level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity, 92%). Combination of TSH and TRAb determinations did not further improve prediction of relapse. Other factors such as gender, age, goiter volume, smoking habits, presence of thyroid-associated ophthalmopathy, and urinary iodine excretion did not show a significant influence on relapse rate.


CONCLUSIONS
Low TSH values 4 weeks after ATDT withdrawal predict relapse of Graves' disease, both early (persistence) and, to a lesser extend, within 2 years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.
Quadbeck
Beate
B
Division of Endocrinology, Department of Medicine University of Duisburg-Essen, Essen, Germany. beate.quadbeck@uni-essen.de
Hoermann
Rudolf
R
Roggenbuck
Ulla
U
Hahn
Susanne
S
Mann
Klaus
K
Janssen
Onno E
OE
D000328:Adult; D000906:Antibodies / Q000032:analysis*; D013956:Antithyroid Agents / Q000627:therapeutic use*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007454:Iodides / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011989:Receptors, Thyrotropin / Q000097:blood*; D012008:Recurrence; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*
D000906:Antibodies; D013956:Antithyroid Agents; D007454:Iodides; D011989:Receptors, Thyrotropin; D013972:Thyrotropin