Background To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database.
Methods We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes.
Results The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m2 were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m2. Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM.
Conclusion The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.
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Background We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants.
Methods We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence.
Results Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS.
Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.
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Background Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients.
Methods Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed.
Results The median daily iodine intake by 24-hour recall was 341.7 μg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine.
Conclusion Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.
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Background Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT).
Methods A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome.
Results Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group.
Conclusion The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.
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Background Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence.
Methods We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies.
Results The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902).
Conclusion Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.
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Endocrinol Metab. 2021;36(3):582-589. Published online June 8, 2021
Background The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors.
Methods We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months.
Results In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer.
Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.
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Endocrinol Metab. 2021;36(3):574-581. Published online May 26, 2021
Background Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
Methods This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.
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Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.
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Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.
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