The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear.

The prevalence and natural history of Graves' orbitopathy (GO) are poorly documented. A large series of 346 patients with newly diagnosed and recent onset Graves' hyperthyroidism seen at a single (nontertiary referral) center over an 8-year period were enrolled in an observational prospective study and evaluated for GO activity and severity according to the EUGOGO (European Group on Graves' Orbitopathy) criteria. After excluding patients immediately treated for moderate-to-severe GO, patients undergoing total thyroidectomy or radioactive iodine treatment, and patients lost to follow-up, 237 patients were submitted to antithyroid drug (ATD) treatment, with ocular evaluation at 6, 12, and 18 months. Among the whole cohort, at presentation 255 (73.7%) had no ocular involvement, 70 (20.2%) had mild and inactive GO, 20 (5.8%) had moderate-to-severe and active GO, and 1 (0.3%) had sight-threatening GO with dysthyroid optic neuropathy. Of the 237 patients who completed the 18-month follow-up during or after ATD treatment, 194 (81.9%) had no GO at baseline. Progression to moderate-to-severe GO occurred in 5 (2.6%) of these patients. Of the 43 (18.1%) patients with mild and inactive GO at baseline, 1 (2.4%) progressed to moderate-to-severe GO, and 25 (58.1%) experienced complete remission. Most patients with newly diagnosed Graves' disease have no ocular involvement. Moderate-to-severe and active GO or sight-threatening GO are rare at presentation and rarely develop during ATD treatment. Most patients (>80%) with no GO at baseline do not develop GO after an 18-month follow-up period. Remission of mild GO occurs in the majority of cases.

It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes. To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Graves ophthalmopathy receiving orbital radiation therapy and glucocorticoids. Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2). University medical center. 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2). In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks). Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy). In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001). Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy.

OBJECTIVE: Thyroid blood flow is greatly enhanced in untreated Graves' disease, but it is not known whether it is due to thyroid hormone excess or to thyroid hyperstimulation by TSH-receptor antibody. To address this issue in vivo patients with different thyroid disorders were submitted to color flow doppler sonography (CFDS). SUBJECTS AND METHODS: We investigated 24 normal subjects, and 78 patients with untreated hyperthyroidism (49 with Graves' hyperthyroidism, 24 with toxic adenoma, and 5 patients with TSH-secreting pituitary adenoma (TSHoma)), 19 patients with thyrotoxicosis (7 with thyrotoxicosis factitia, and 12 with subacute thyroiditis), 37 euthyroid patients with goitrous Hashimoto's thyroiditis, and 21 untreated hypothyroid patients with Hashimoto's thyroiditis. RESULTS: Normal subjects had CFDS pattern 0 (absent or minimal intraparenchimal spots) and mean intraparenchimal peak systolic velocity (PSV) of 4.8+/-1.2cm/s. Patients with spontaneous hyperthyroidism due to Graves' disease, TSHoma, and toxic adenoma had significantly increased PSV (P<0.0001, P=0.0004, P<0.0001 respectively vs controls) and CFDS pattern. Patients with Graves' disease had CFDS pattern II (mild increase of color flow doppler signal) in 10 (20%) and pattern III (marked increase) in 39 cases (80%). Mean PSV was 15+/-3cm/s. Patients with toxic adenoma had CFDS pattern I (presence of parenchymal blood flow with patchy uneven distribution) in 2 (8%), pattern II in 16 (70%) and pattern III in 5 (22%). Mean PSV was 11+/-2.4cm/s. Patients with TSHoma showed CFDS pattern I in one case (20%) and pattern II in 4 (80%). Mean PSV was 14.8+/-4.2cm/s. Patients with thyrotoxicosis had normal PSV (4.2+/-1. 1cm/s in subacute thyroiditis, 4+/-0.8cm/s in thyrotoxicosis factitia, P=not significant vs controls) and CFDS pattern 0. Untreated euthyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern 0, and mean PSV (4.3+/-0.9cm/s; P=not significant vs controls). Untreated hypothyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern I in 14 cases (67%), pattern II in 4 (19%) and pattern 0 in 3 (14%) and mean PSV (5.6+/-1. 4cm/s) was higher than that of controls (P=0.026). CONCLUSIONS: An increase in both intrathyroidal vascularity and blood velocity was observed in patients with spontaneous hyperthyroidism but not in thyrotoxicosis due to either ingestion of thyroid hormones or to a thyroidal destructive process. The slightly increased vascularity and blood velocity observed in patients with hypothyroid Hashimoto's thyroiditis suggests that thyroid stimulation by either TSH-receptor antibody or TSH is responsible for the increased thyroid blood flow.

Context: Radioiodine (RAI) therapy may cause progression of mild or absent Graves’ orbitopathy (GO), preventable by oral prednisone. Optimal doses of prednisone are undefined. Objective: The aim of this study was to compare the effectiveness of reported doses [starting dose, >0.3 mg/kg body weight (bw)], and lower (<0.3 mg/kg bw)] doses of prednisone. Design and Setting: We conducted a retrospective matched cohort study at a University Center. Patients: Of 111 RAI-treated Graves’ patients with mild or no GO, 35 received no steroid prophylaxis (absence of GO and/or risk factors for RAI-associated GO progression); 28 received low-dose prednisone (starting dose, 0.16–0.27 mg/kg bw; mean ± sd, 0.22 ± 0.03 mg/kg bw; group 1); and 48 received higher doses (group 2). Among the latter, 28 (starting dose, 0.32–0.56 mg/kg bw; mean ± sd, 0.36 ± 0.05 mg/kg bw) were matched with group 1 according to several relevant variables. Prednisone was started 1 d after RAI and withdrawn after 6 wk. Main Outcome Measures: We assessed ocular changes (1, 3, and 6 months after RAI) and side effects of prednisone. Results: Two of 35 patients not receiving steroid prophylaxis (6%) developed mild-to-moderate GO (clinical activity score, 2/7 and 3/7) after RAI. No patients in group 1 or group 2 had GO progression. Side effects were very mild and inconstant, although more frequent in group 2. Both groups showed an increase in bw, an increase that was significantly higher in group 2. Conclusion: Lower doses of oral prednisone (about 0.2 mg/kg bw) are as effective as previously reported doses (0.3–0.5 mg/kg bw). A shorter treatment period (6 wk) is probably sufficient. The increase in bw is less using lower doses of prednisone.