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It has been reported that Graves' disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.