TRAb elevations occurred even in the third trimester; a case of a mother of a child with neonatal thyroid dysfunction, who received radioactive iodine therapy for Graves' disease.

Activity of Graves' disease (GD) is known to improve during gestation, as values of thyrotropin (TSH) receptor antibody (TRAb) also improve. However, the risk of neonatal hyperthyroidism increases when maternal TRAb values are high in the second to third trimester. A 29-year-old woman who had undergone radioactive iodine (RAI) therapy for GD 10 years earlier visited our hospital at 17 weeks of gestation, showing subclinical hypothyroidism and a positive TRAb value of 2.6 IU/L (reference range, <2.0 IU/L). Thyroid hormone replacement therapy was commenced and thyroid function normalized within 4 weeks, although TRAb was elevated at the time (3.8 IU/L). Prenatal check-up showed normal growth development and no irregularities. At 29 weeks of gestation, serum TRAb was extremely elevated, up to 16.8 IU/L. Since the risk of neonatal hyperthyroidism was of great concern, delivery was planned at an advanced-care medical center. At 38 weeks 5 days of gestation, she delivered a female neonate without any complications, although blood testing of the neonate showed subclinical hyperthyroidism with positive TRAb and TSH receptor stimulating antibody (TSAb). According to the American Thyroid Association guidelines, the TRAb value should be checked in the third trimester if mothers show a TRAb elevation between the initial visit after pregnancy and 18-22 weeks of gestation. However, if the mother has a history of RAI therapy for GD, regardless of thyroid function during gestation, the possibility of TRAb values elevating over time even years after the definitive therapy must be considered.

Therapeutic efficacy and limitations of potassium iodide for patients newly diagnosed with Graves' disease.

The efficacy of potassium iodide (KI) for Graves' disease (GD) has been reported, although few clinical reports have examined the long-term efficacy of treatment. The objective of this study was to investigate the efficacy and limitations of KI treatment for GD. This study enrolled patients newly diagnosed with mild GD, defined as free thyroxine (FT4) <5.0 ng/dL, between July 2014 and June 2016. KI was started at a dose of 50 mg/day, and if FT4 values did not decrease after initiation of treatment, doses were increased to 100 mg/day. Patients for whom thyroid hormone levels could not be controlled with KI at 100 mg/day were regarded as non-responders. Of the 122 patients (13 males, 109 females) included in this study, 71 (58.2%) responded to KI therapy. The remaining 51 patients (41.8%) were non-responders. The median duration required to judge non-responsiveness was 5.9 months. Multiple logistic regression analysis performed on parameters measured at the initial visit indicated FT4 (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28-3.75; p = 0.0007) and male sex (OR 3.58, 95%CI 1.04-12.3; p = 0.04) were significantly associated with KI responsiveness. Receiver operating characteristic (ROC) curve analysis of the relationship between FT4 and KI responsiveness indicated an FT4 cut-off of 2.76 ng/dL was optimal for differentiating between responders and non-responders. KI therapy was effective and safe for about 60% of patients with mild GD.

Analysis of Antithyroid Drug-Induced Severe Liver Injury in 18,558 Newly Diagnosed Patients with Graves' Disease in Japan.

Background: The prevalence of antithyroid drug (ATD)-related drug-induced liver injury (DILI) has been reported to vary among patients in several countries. The purpose of this study was to summarize the prevalence of liver injury induced by ATD and to determine the actual prevalence of severe liver injury. Methods: The medical records of 18,558 patients who were newly diagnosed with Graves' disease between January 2005 and December 2016 were retrospectively reviewed. Severe DILI was defined as alanine aminotransferase (ALT) 8 times higher than the upper limit of normal (ULN) or total bilirubin (T-bil) 3 times higher than the ULN. The most severe DILI was defined as ALT higher than 20 times the ULN or T-bil higher than 10 times the ULN. Results: A total of 461 subjects (470 cases) were analyzed, and they consisted of 10 males and 451 females, with a median age of 37 years (range 10-82 years). Nine of 461 patients had severe DILI with both drugs. The total prevalence of severe DILI in this study was 2.5%, and the prevalence of DILI by drug was 1.4% with metimazole (MMI) (n = 198) and 6.3% with propylthiouracil (PTU) (n = 272) (p < 0.001). The prevalence of the most severe ATD-related DILI was 0.22% (n = 40), and the prevalence for each drug was 0.08% with MMI (n = 11) and 0.68% with PTU (n = 29). The median time to DILI development was 30 days (range 7-314 days), and all patients recovered from DILI, with no fatalities. The prevalence of MMI-related DILI was significantly age dependent (p < 0.001). Conclusions: Though there were no fatalities in this study, the prevalence of PTU-related severe DILI was significantly higher than that of MMI-related severe DILI.