Cardiac Troponin Is Elevated in Patients with Thyrotoxicosis and Decreases as Thyroid Function Improves and Brain Natriuretic Peptide Levels Decrease.

INTRODUCTION: High-sensitive cardiac troponin reflects micro-myocardial injury in the absence of overt myocardial infarction. OBJECTIVE: This study aimed to clarify how thyrotoxicosis affects cardiac troponin. METHODS: This was a prospective observational study in Japan. Untreated patients with thyrotoxicosis who visited Ito Hospital were enrolled, and medical treatment was initiated for hyperthyroidism. Thyroid function, high-sensitive troponin I (hsTnI), and brain natriuretic peptide (BNP) were measured at baseline and then every 3 months for 1 year. RESULTS: Data from a total of 143 patients (median age, 42 years; 32 men and 111 women) were investigated. At baseline, median hsTnI was 1.9 pg/mL and ranged from 0 to 69.6 pg/mL. Five patients (3.5%) had a high hsTnI value that exceeded 26.2 pg/mL, which is used as the cutoff for diagnosis of myocardial infarction, and 22 patients (15.4%) had an intermediate value between 5.0 and 26.2 pg/mL. Multivariable regression analysis showed that significant predictors of the hsTnI value were age (ß = 0.20, p = 0.01) and BNP (ß = 0.43, p < 0.0001) (R2 = 0.27, F = 26.0, p < 0.0001), and significant predictors of the BNP value were age (ß = 0.23, p = 0.001), hemoglobin (ß = -0.43, p < 0.0001), free T4 (FT4) (ß = 0.23, p = 0.001), and hsTnI (ß = 0.27, p < 0.0001) (R2 = 0.49, F = 33.8, p < 0.0001). Correlations were found between a decrease in hsTnI and BNP in the first 3 months (ρ = 0.49, p < 0.0001). A decrease in FT4 in the first 3 months was weakly correlated with decreases in hsTnI (ρ = 0.32, p = 0.0004) and BNP (ρ = 0.32; p = 0.0003). Of the 27 patients with elevated hsTnI (≥5.0 pg/mL), the hsTnI level was normalized in 20 patients within a year. CONCLUSIONS: In thyrotoxicosis, the myocardial biomarker hsTnI is elevated in about 20% of patients; hsTnI levels decrease as thyroid function improves and BNP decreases.

Reconfirmation of the accuracy of the taller-than-wide sign in multicenter collaborative research in Japan.

The taller-than-wide sign indicates that the anteroposterior dimension-to-transverse dimension ratio (AP/T ratio) is higher than 1. The aim of the present study was to reconfirm the accuracy of the taller-than-wide sign for diagnosing malignant thyroid nodules by ultrasonography in multicenter collaborative research, and investigate differences according to tumor sizes, histological types, and the influence of the tilt and orientation of the probe. At 6 registered institutes, 2,032 thyroid nodules were successively operated on and diagnosed pathologically. The accuracy of the taller-than-wide sign for diagnosing malignant tumors by ultrasonography was retrospectively analyzed across all nodules as well as in analyses separately stratified by tumor size and histology. The influence of the tilt and orientation of the probe was also assessed. The taller-than-wide sign showed high specificity for diagnosing malignancy in all nodules tested. It also showed high specificity regardless of the tumor size. When tumors were analyzed by histological types, the AP/T ratio of papillary carcinoma was significantly higher than that of benign nodules, whereas no significant difference was observed between follicular carcinoma and benign nodules. The specificity of longitudinal sections was significantly higher, while the AUC of longitudinal sections was significantly larger than those of transverse sections. The AP/T ratio obtained when the probe was tilted was not significantly different from that when it was straight. The present results support the usefulness of the taller-than-wide sign for diagnosing malignant tumors regardless of size, but not follicular carcinoma. The influence of the tilt and orientation of the probe was negligible.

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.

Characteristics of Patients with Graves' Disease Whose Thyroid Hormone Levels Increase After Substituting Potassium Iodide for Methimazole in the First Trimester of Pregnancy.

Background: The clinical course of Graves' disease (GD) in women who switched from methimazole (MMI) to potassium iodide (KI) during the first trimester of pregnancy has never been reported in detail. Objective: To investigate the characteristics of GD patients whose thyroid hormone levels increase after substituting KI for MMI. Patients: Two hundred forty women with GD who had been treated with MMI and switched from MMI to inorganic iodide to control hyperthyroidism during the first trimester between January 1, 2005, and March 31, 2018. Results: In 133 (55.4%) of the GD patients, medication was completely tapered during pregnancy, and the other 107 (44.6%) GD patients were taking medication at delivery: 57 were taking KI alone and 50 were taking an antithyroid drug with or without KI. It was difficult to control the maternal thyrotoxicosis of 22 of the 107 patients with KI alone, and a higher dose of MMI compared with the dose at the time of conception was required (worsened group). Multivariate analysis revealed that the TRAb value at the time of switch from MMI to KI was the only factor that predicted continuation of the thyroid suppression medication, but none of the parameters was a predictor of the worsened group. Conclusions: It must be kept in mind that a certain proportion of GD patients escape from the antithyroid effect of iodide and that careful follow-up is necessary after switching a pregnant patient's medication to KI.

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.

Incidence of Neonatal Hyperthyroidism Among Newborns of Graves' Disease Patients Treated with Radioiodine Therapy.

BACKGROUND: The serum thyrotropin receptor antibody (TRAb) titers of Graves' disease (GD) patients are known to increase after radioiodine (RAI) therapy, and they can remain high for years. The incidence of neonatal hyperthyroidism (NH) among newborns of mothers with GD who conceived after RAI therapy has not been previously reported. The aims of this study were to investigate the incidence of NH among newborns of mothers who conceived within two years after RAI therapy, and to identify predictors of NH. METHODS: GD patients (n = 145) who conceived within two years after RAI therapy were retrospectively reviewed, and information regarding their newborns was collected. RESULTS: Of the 145 pregnant women, 54 (37%) were treated with antithyroid drugs or potassium iodide for maternal hyperthyroidism during the first trimester. There were eight newborns with NH, resulting in an incidence of 5.5%. Seven of the eight mothers whose newborns had NH were treated with antithyroid drugs or potassium iodide during their pregnancy. The incidence of NH among the newborns of mothers who conceived within 6-12 months after RAI therapy was 8.8%, within 12-18 months was 5.5%, and within 18-24 months was 3.6%. Multivariate analysis revealed that the TRAb values in the third trimester were the only risk factor for NH. The cutoff TRAb value in the third trimester for predicting NH was 9.7 IU/L (reference value <2.0 IU/L). CONCLUSIONS: The incidence of NH among newborns of mothers who conceived within two years after RAI therapy was 5.5%. The fetuses of pregnant GD patients whose TRAb value is high in the third trimester should be carefully followed by an obstetrician during pregnancy, and the newborns should be carefully followed by a pediatrician after birth.

Clinical course of thyroid function and thyroid associated-ophthalmopathy in patients with euthyroid Graves' disease.

BACKGROUND: Euthyroid Graves' disease (EGD) is a rare condition defined as the presence of thyroid-associated ophthalmopathy (TAO) in patients with normal thyroid function. Due to the rarity of this disease, only a limited number of studies and case reports are available for further evaluation of the characteristics of the disease. The aim of this study was to examine the changes in the thyroid function, thyrotropin receptor antibodies (TRAb) and eye symptoms, and then determine whether TRAb is related to TAO in EGD patients. TRAb in this study was defined as including both thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSAb). PATIENTS AND METHODS: Medical records of patients diagnosed with EGD were reviewed. Ophthalmologists specializing in TAO examined the eyes of all subjects. RESULTS: Of the 58 patients diagnosed with EGD, 24.1% developed hyperthyroidism, while 3.4% developed hypothyroidism. A total of 72.4% of the 58 patients remained euthyroid throughout the entire follow-up period. At the initial presentation, TBII and TSAb were positive in 74.5% and 70.5%, respectively. Ophthalmic treatments were administered to 30 (51.7%) out of the 58 patients. A significant spontaneous improvement of the eye symptoms was found in 28 of the EGD patients who did not require eye treatments. EGD patients exhibited positive rates for both TBII and TSAb, with the number of the TRAb-positive patients gradually decreasing while the eye symptoms spontaneously improved over time. There were no correlations found between TRAb at initial presentation and the eye symptoms. CONCLUSION: TBII and TSAb were positive in about 70% of EGD patients at their initial visit. Thyroid functions of EGD patients who have been euthyroid for more than 6.7 years may continue to remain euthyroid in the future.

Seasonal Changes in Serum Thyrotropin Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan.

BACKGROUND: This study analyzed big data for serum thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations in patients who had attended the outpatient clinic of Ito Hospital (Tokyo, Japan) during a recent six-year period (between January 1, 2010, and December 31, 2015) in order to investigate for seasonal changes. METHODS: The serum TSH concentrations were reviewed for all 135,417 patients aged >20 years. Patients with any thyroid diseases were included, irrespective of whether they were receiving drug therapy. In total 1,637,721 serum samples were analyzed for TSH, 1,626,269 for fT3, and 1,669,381 for fT4. RESULTS: It was observed that the TSH concentrations showed annual changes during the six-year period. They decreased during the summer, while they increased during the winter. The TSH concentrations were negatively correlated with the daily temperatures (Spearman rank correlation coefficient -0.4486; p < 0.0001). The same applied for the correlation between fT3 concentrations and daily temperatures. CONCLUSIONS: The fact that the TSH concentrations show annual changes in areas where the temperature ranges during the year are rather wide should be borne in mind for interpretation of results.

Long-Term Outcomes of 107 Cases of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma at a Single Medical Institution in Japan.

Context: Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis. Objective: To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma. Design, Setting, and Participants: Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed. Main Outcome Measure: Overall and event-free survival (EFS). Results: Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively. Conclusions: Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.

The characteristics of osteoporotic patients in Graves' disease patients newly diagnosed after menopause: a prospective observational study.

Overt hyperthyroidism is associated with reduced bone density. The extent of restoration of reduced bone density caused by hyperthyroidism in postmenopausal Graves' disease (GD) patients has not fully been investigated. We examined 85 newly diagnosed postmenopausal GD patients, and we measured their serum thyroid hormone levels as well as their bone turnover marker levels and the bone mineral density (BMD) of their lumbar spine (LS), both femoral necks (FN), and left distal radius (DR). We prospectively observed the patients for changes in BMD and bone turnover marker levels during a 24-month period after euthyroidism had been established by ATD treatment. The median age of the subjects was 57 years old (range: 50 to 79). 46 (54.1%) patients had osteoporosis. 42 of the 46 osteoporosis patients had low BMD in the DR. The patients with osteoporosis were significantly older, had a significantly lower BMI, and had significantly higher bone turnover marker levels compared to the normal BMD patients. The best predictor of the BMD in the DR was BMD in the FN (ß = 0.40, p < 0.0001). A total of 42 patients were followed up for 24 months after attainment of euthyroidism, and 19 of them were osteoporosis at the first visit. The BMD of the 19 osteoporotic patients had increased by 4.9% in the LS, 11.9% in the FN, and 9.3% in the DR at 24 months. After maintaining a euthyroid state for 24 months by means of ATD treatment, 26% of the osteoporotic patients had recovered from osteoporosis.

TSH receptor antibody titers measured with a third-generation assay did not reflect the activity of Graves' ophthalmopathy in untreated Japanese Graves' disease patients.

TSH receptor antibody (TRAb) titer has been reported to be correlated with Graves' ophthalmopathy (GO). However, the correlation between GO activity and TRAb titer assessed with a third-generation assay has not been reported. We enrolled 238 untreated Graves' disease patients who came to the outpatient clinic of Ito Hospital and 28 patients who were euthyroid. All of the patients were assessed for GO by an ophthalmologist within 3 months of their initial visit to Ito Hospital. Clinical activity score (CAS), short inversion time inversion recovery (STIR), and sum of the maximum external orbital muscle areas (SEOMA) on a frontal sectional magnetic resonance imaging (MRI). The TRAb titer was significantly higher in patients with inactive ophthalmopathy (the inactive-GO group) than in patients with active ophthalmopathy (the active-GO group) (17.7 ± 13.5 IU/L vs. 13.0 ± 13.1 IU/L, p=0.0082). The SEOMA values were not correlated with TRAb titer. The prevalence of active-GO was higher in euthyroid patients than in hyperthyroid patients although the difference was not significant. In conclusion, TRAb titer measured with a third-generation assay dose not correlate with GO activity based on MRI findings in untreated Graves' disease patients, and the prevalence of active-GO is higher in euthyroid patients with lower TRAb titers than in hyperthyroid patients.

Inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake in healthy Japanese adults.

In the event of a nuclear power plant accident, prophylactic administration of potassium iodide (KI) is recommended to prevent thyroid damage due to uptake of radioiodine. To assess the inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake (RAIU) in healthy adults without dietary iodine restriction, single or repeated doses of 10 mg inorganic iodine solution were given to 22 Japanese volunteers, 18 men and 4 women with the mean age of 35.7 years, between 2011 and 2013. Changes in urinary iodine excretion, thyroid function and 24-hour RAIU were also evaluated. The median 24-hour RAIU without iodine restriction was 13% (range, 5-26%). A single-dose of 10 mg inorganic iodine suppressed the median 24-hour RAIU measured one hour after iodine administration to 3% (range, 1-7 %) and, in 90.9% of 22 participants their 24-hour RAIU was < 5%. For seven participants given 10 mg of inorganic iodine daily for 14 days, the median 24-hour RAIU measured at 24 hours after the last administration of iodine was 6% (range, 2-12%), although the inhibitory effect was diminished in two participants. Serum thyroid stimulating hormone concentration was slightly elevated in three participants without decreased serum FT3 and FT4 levels. We conclude that a single-dose of 10 mg inorganic iodine is sufficient to inhibit RAIU in adults, although the inhibitory effect of repeated-dose on RAIU is diminished when KI is given once daily. The dose, duration or interval of iodine administration should be evaluated in iodine-sufficient regions in a future.

Substituting Potassium Iodide for Methimazole as the Treatment for Graves' Disease During the First Trimester May Reduce the Incidence of Congenital Anomalies: A Retrospective Study at a Single Medical Institution in Japan.

BACKGROUND: To control hyperthyroidism due to Graves' disease, antithyroid drugs should be administered. Several studies have shown that exposure to methimazole (MMI) during the first trimester of pregnancy increases the incidence of specific congenital anomalies that are collectively referred to as MMI embryopathy. Congenital anomalies associated with exposure to propylthiouracil (PTU) have also recently been reported. METHODS: This study investigated whether substituting potassium iodide (KI) for MMI in the first trimester would result in a lower incidence of major congenital anomalies than continuing treatment with MMI alone. The cases of 283 women with Graves' disease (GD) were reviewed whose treatment was switched from MMI to KI in the first trimester (iodine group), as well as the cases of 1333 patients treated with MMI alone (MMI group) for comparison. Another major outcome of interest was the incidence of neonatal thyroid dysfunction. The subjects of the analysis of major congenital anomalies and neonatal thyroid dysfunction were live-born infants. RESULTS: The incidence of major anomalies was 4/260 (1.53%) in the iodine group, which was significantly lower than the incidence of 47/1134 (4.14%) in the MMI group. Two neonates in the iodine group had anomalies consistent with MMI embryopathy (0.8%), as opposed to 18 neonates in the MMI group (1.6%). None of the neonates exposed to KI had thyroid dysfunction or goiter. CONCLUSIONS: Substituting KI for MMI as a means of controlling hyperthyroidism in GD patients during the first trimester may reduce the incidence of congenital anomalies, at least in iodine-sufficient regions.

Radioiodine-Associated Exacerbation of Graves' Orbitopathy in the Japanese Population: Randomized Prospective Study.

CONTEXT: Exacerbation of Graves' orbitopathy (GO) after radioiodine (RAI) therapy has been examined in some populations but has not been fully described in Japanese populations. OBJECTIVE: The purpose of this study was to clarify the characteristics of GO exacerbation after RAI therapy and the effectiveness of low-dose prophylactic corticosteroid (PCS). DESIGN AND SETTING: This was a prospective randomized study in Tokyo, Japan. PATIENTS: Between June 2011 and June 2012, 295 patients with Graves' disease with either inactive GO or no GO received RAI therapy. Of these, 147 received no PCS (PCS-Off group), whereas 148 received low-dose PCS (starting dose, 15 mg/day of prednisolone) for 6 weeks (PCS-On group). We used magnetic resonance imaging to thoroughly evaluate GO before and 1 year after RAI therapy. MAIN OUTCOME MEASURES: Outcomes of GO 1 year after RAI therapy were determined. RESULTS: GO exacerbation occurred in 29 patients (9.8%), and only 7 patients (2.4%) required ophthalmic treatment. No significant difference in the frequency of GO exacerbation was seen between the groups (PCS-On group: n = 18 [12.1%]; PCS-Off group: n = 11 [7.5%]; P = .17). Significant prognostic factors were identified as thyroid-stimulating antibody (by 100% linear increase: risk ratio, 1.15; 95% confidence interval, 1.07-1.24; P = .0003) and clinical activity score (≥1 vs 0: risk ratio, 6.40; 95% confidence interval, 2.17-19.7; P = .0009). CONCLUSION: Exacerbation of GO after RAI therapy in the Japanese population appears less common than in other populations. Low-dose PCS did not produce a significant preventive effect and appeared insufficient. Patients presenting with risk factors would thus be recommended to receive higher-dose PCS.

Serum human chorionic gonadotropin levels and thyroid hormone levels in gestational transient thyrotoxicosis: Is the serum hCG level useful for differentiating between active Graves' disease and GTT?

Gestational transient thyrotoxicosis (GTT) is defined as transient thyrotoxicosis caused by the stimulating effect of human chorionic gonadotropin (hCG) during pregnancy. We attempted to identify the serum hCG level that causes GTT, and we compared the serum hCG levels and thyroid hormone levels of GTT patients according to whether they had a background of thyroid disease. We also evaluated serum hCG as a parameter for differentiating between active Graves' disease (GD) and GTT. We reviewed the 135 cases of pregnant women who came to our hospital to be evaluated for thyrotoxicosis during their 7th to 14th week of pregnancy, and their serum hCG level was measured at that time. Among the 135 pregnant women with thyrotoxicosis; 103 of the women had GTT, and the other 32 women had active GD. There were no correlations between their serum hCG levels and free thyroid hormone levels. There were no significant differences in thyroid hormone levels or hCG levels among the GTT groups with different thyroid disease backgrounds; i.e., the GTT group without thyroid disease, GTT group with chronic thyroiditis, GTT group with non-functioning thyroid nodules, and GTT group with GD in remission. The serum hCG level of the GTT group was significantly higher than in the active GD group, but it was not a good parameter for differentiating between the two groups. The FT3/FT4 ratio of the active GD was significantly higher than in GTT group, and was a better parameter for differentiation.

Comparison of efficacy and adverse effects between methimazole 15 mg+inorganic iodine 38 mg/day and methimazole 30 mg/day as initial therapy for Graves' disease patients with moderate to severe hyperthyroidism.

BACKGROUND: Methimazole (MMI) is usually used at an initial dose of 30 mg/day for severe Graves' disease (GD) hyperthyroidism, but adverse effects are more frequent at this dose than at MMI 15 mg/day. OBJECTIVES: We designed a regimen to address the lack of a primary therapeutic effect of the MMI 15 mg/day by combining it with inorganic iodine at 38.2 mg/day. Our aim was to compare the two regimens (MMI 15 mg+inorganic iodine at 38.2 mg/day (M15+I) vs. MMI 30 mg/day (M30)) in terms of therapeutic effect, adverse effects, and remission rate. DESIGN AND PATIENTS: In a prospective study, 310 patients with untreated GD (serum free thyroxine (fT4) ≥5 ng/dL) were assigned to one of the two regimens. Potassium iodide was discontinued in the M15+I group as soon as the serum fT4 level was within the reference range (0.8-1.6 ng/dL). RESULTS: Percentages of patients achieving an fT4 level within reference range in ≤30, ≤60, or 90 days on the study treatment regimens were 45.3%, 73.9%, and 82.0% respectively for the M15+I group, and 24.8%, 63.1%, and 75.2% respectively for the M30 group. Hence, the proportions of patients achieving this goal in ≤30 or ≤60 days were significantly larger in the M15+I group. Adverse effects that required discontinuation of MMI were more frequent in the M30-treated than in the M15+I-treated group (14.8% vs. 7.5%; p=0.0387). The remission rates in the M15+I and M30 groups were 19.9% and 14.8%-higher in the former, but the difference did not reach statistical significance. CONCLUSION: The results of this study raise the possibility that M15+I is superior to M30 as a primary treatment for moderate to severe hyperthyroidism caused by GD.

Changes in pediatric thyroid sonograms in or nearby the Kanto region before and after the accident at the Fukushima Daiichi nuclear power plant.

Following the accident at the Fukushima Daiichi Nuclear Power Station which occurred on March 11, 2011 due to the Eastern Japan Great Earthquake (the Accident), there have been concerns over elevation of the risk of thyroid cancer among children due to internal exposure to radioactive iodine. In Fukushima Prefecture, screening of children with thyroid ultrasonography has been carried out, yielding numerous findings, suggesting a possible influence from the Accident. We report thyroid ultrasonographic findings, used by similar device at Fukushima Prefecture's study, at Ito-hospital. Of the 2721 children aged 15 or less who visited our hospital between January 2005 and March 2013, 1214 children (330 boys and 884 girls; median age, 12; range of age, 4-15) were covered by evaluation of thyroid ultrasonographic findings, excluding children known in advance to have thyroid disease on the basis of disease history, palpation and blood tests. Among these 1214 children, 709 children (58.4%) were found cysts (≤ 5 mm in 665 cases) by ultrasonography, 43 children (3.5%) were found nodules (≤ 5 mm in 18 cases) and 9 children (5.2%) were found an intrathyroid ectopic thymus. Analysis of the data before and after the Accident using the same device, involving age adjustment on the basis of the standard population in 2010, showed no difference in the incidence rate of cysts or nodules. In children examined, the incidence rate of cyst formation (particularly ≤ 5 mm) was higher, and there was no difference in the incidence rate of cysts or nodules between the pre- and post-accident period.

Lower incidence of postpartum thyrotoxicosis in women with Graves disease treated by radioiodine therapy than by subtotal thyroidectomy or with antithyroid drugs.

PURPOSE OF THE REPORT: The incidence of postpartum thyrotoxicosis (PT) in Graves disease (GD) patients treated with antithyroid drugs (ATDs) is higher than in the general population, but the incidence of PT among GD patients who had been treated with radioiodine (RI) or by subtotal thyroidectomy before their pregnancy is not well known. SUBJECTS AND METHODS: We reviewed the cases of women with GD who had become pregnant, and we selected the 188 women who had undergone RI therapy before the pregnancy and the 148 women who had undergone subtotal thyroidectomy for GD before the pregnancy as the subjects of this study. The ATD subjects were 107 women with GD who had become pregnant after being treated with ATDs alone before their pregnancy and were in remission before and throughout the pregnancy. RESULTS: The overall incidence of PT was 2.1% (4/188) in the RI group, 23.6% (35/148) in the subtotal thyroidectomy group, and 55.1% (59/107) in the ATD group. There were no cases of permanent thyrotoxicosis in the RI group. CONCLUSIONS: The incidence of PT among women with GD who have undergone RI therapy before their pregnancy was significantly low compared to thyroidectomy group and ATD group. This finding is interesting because the incidence of PT in the RI group was lower than subtotal thyroidectomy group even though thyroid volume had been greatly reduced by thyroidectomy. RI treatment is recommended in the choice of treatment for childbearing-age women as regards the risk of postpartum recurrence.

Rituximab-including combined modality treatment for primary thyroid lymphoma: an effective regimen for elderly patients.

BACKGROUND: Primary thyroid lymphoma (PTL) develops mostly in middle-aged and older females. However, the optimal treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL), which accounts for most PTL cases, is unclear. Rituximab is a promising drug that, in combination with traditional combination therapy, has demonstrated an increased antitumor effect without a substantial increase in toxicity. In this study, treatment outcomes of elderly patients with thyroid DLBCL who underwent rituximab-including combination therapy were analyzed. METHOD: Between January 2005 and December 2011, 43 patients 60 years of age or older (median 71 years, range 60-80 years) were diagnosed as having stage IE (n=12) or stage IIE (n=31) DLBCL, and three courses of R-CHOP therapy (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2, and prednisolone 100 mg/body) and involved field irradiation were planned. Treatment outcomes of these patients were retrospectively reviewed. RESULTS: Two patients terminated the treatment because of interstitial pneumonia during R-CHOP therapy. Only one patient showed treatment resistance and the regimen was changed; 42 patients (98%) responded to the treatment. Five-year overall survival and event-free survival were 87% (95% confidence interval [95% CI], 64-96%) and 74% (95% CI, 50-89%), respectively. CONCLUSION: The results of the present study indicate that rituximab-including combination therapy was effective for elderly patients with thyroid DLBCL. A multicenter, long-term observational study is needed to confirm this, and additional refinement of the treatment protocol is required to optimize the antitumor effect.

Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy.

The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves' disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low.