Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves’ disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Background: G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress. Methods: Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium. Results: In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. Conclusion GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Background: Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults. Methods: Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638). Results: This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively. Conclusion Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Background: Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults. Methods: Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638). Results: This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively. Conclusion Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Background: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. Methods: The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. Results: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). Conclusion The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.