Treatment of Graves' disease: effects of the administration of L-thyroxine associated with methimazole as a single daily dose.
OBJECTIVE
To reduce the number of tablets to be administered daily during antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the effectiveness of adding thyroxine after the patients had become euthyroid during methimazole therapy.


METHODS
All patients were given gelatin capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken once a day for 18-24 months. Thirty patients with Graves' disease without previous treatment for hyperthyroidism were included. Two were lost to follow-up and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed for 18 to 24 months with methimazole and thyroxine medication plus an additional 2 years after the treatment was suspended. After completion of the study the patients were, retrospectively, divided in two groups: group 1 (G1, n = 20) patients considered to be in remission, and group 2 (G2, n = 8) with persistent active Graves' disease.


RESULTS
All patients in group 1 had a significant reduction in the glandular mass, as estimated by ultrasonographic studies (mean +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g). Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin concentrations did not decrease significantly after therapy (58 +/- 20 micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/- 5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after treatment withdrawal, indicating a remission rate of 67.8%.


CONCLUSIONS
The administration of L-thyroxine during anti-thyroid drug treatment, with subsequent inhibition of thyroid-stimulating hormone secretion, may be an important factor in glandular mass reduction, decreasing both the production of antibodies to thyroid-stimulating hormone receptors and the frequency of recurrence of hyperthyroidism.
Perozim
L M
LM
Thyroid Laboratory, Hospital das Clínicas, University of Sao Paulo Medical School, Brazil.
Lima
N
N
Knobel
M
M
Cavaliere
H
H
Medeiros-Neto
G
G
D000293:Adolescent; D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008713:Methimazole / Q000008:administration & dosage*; D008875:Middle Aged; D010349:Patient Compliance; D013954:Thyroglobulin / Q000097:blood; D013961:Thyroid Gland / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage*
D013963:Thyroid Hormones; D008713:Methimazole; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine