The evolution of Graves’ ophthalmopathy during treatment with antithyroid drug alone and combined with triiodothyronine

Abstract

We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.

Has the Use of Antithyroid Drugs for Graves' Disease Become Obsolete?

“…The latter group had a greater degree of improvement in both eye signs and proptosis, directly analogous to the beneficial results of employ¬ ing supplemental thyroxine in the study of Hashizume et al (125). CONCLUSIONS I am confident that the fascinating reports of Hashizume et al (125,126), Bromberg et al (127), and Tallstedt et al (86) will spawn a large number of studies that will confirm and clarify the significance of their results. In the meantime, perhaps we should consider earlier combination therapy with replacement thyrox¬ ine in these patients.…”

“…Nevertheless, some support for the importance of maintain¬ ing a normal serum TSH or perhaps avoiding even transient hypothyroidism derives as well from the report of Bromberg et al that examined the course of ophthalmopathy in a group of patients treated with customary doses of antithyroid drugs versus a group treated with larger doses supplemented with triiodothyronine (127) to maintain euthyroidism. The latter group had a greater degree of improvement in both eye signs and proptosis, directly analogous to the beneficial results of employ¬ ing supplemental thyroxine in the study of Hashizume et al (125).…”

Direct effect of propylthiouracil on progesterone release in rat granulosa cells

“…These results suggest that PTU may directly act on the rat granulosa cells to regulate progesterone production and at a point distal to the formation of cAMP (Figure 1). The clinical dosage of PTU is 100–300 mg (Bromberg et al ., 1992). In accordance with the molecular weight of PTU (MW=170.2), the plasma concentration of PTU in patients was approximately 0.24–0.72 m M .…”

Effect of Addition of Thyroxine in the Treatment of Graves’ Disease: A Systematic Review

“…Bromberg et al. compared the effects of the B&R regimen and titration therapy on Graves’ ophthalmopathy, and the results showed no significant difference in the improvement of Graves’ ophthalmopathy ( 17 ). Vaidya et al.…”