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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.
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Objective@#This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). @*Methods@#This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment. @*Results@#The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (−22.9±2.6% vs. −15.6 ± 2.5% [p=0.041] and −24.2±2.5% vs. −12.9±2.4% [p=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [p=0.012] and 76.2% vs. 50.8% [p<0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups. @*Conclusion@#Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy.
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Background@#This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. @*Methods@#This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. @*Results@#The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. @*Conclusion@#In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.
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Background@#Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. @*Methods@#We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. @*Results@#Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. @*Conclusion@#The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
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Background@#To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM). @*Methods@#We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age. @*Results@#Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles. @*Conclusion@#In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.
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Objectives@#In South Korea, a significant number of patients with obstructive sleep apnea have benefited from the insured continuous positive pressure for sleep apnea as of 2018. However, there is limited information on public awareness of sleep apnea syndrome in the country. A nationwide survey was conducted to evaluate the current status of public awareness on the diagnosis and treatment of sleep apnea. @*Methods@#We conducted an online survey using structured questionnaires on symptoms and knowledge of diagnosis and treatment modalities for sleep apnea. A total of 4,000 participants aged 21 to 69 were proportionally allocated according to the residential area, gender, and age group. @*Results@#The STOP questionnaire, a screening tool for sleep apnea, revealed that 1,044 (21.6%) scored ≥2 points, 327 (8.1%) scored ≥3 points, and 64 (1.6%) scored 4 points. However, only 19 of the 1,044 patients were being treated for sleep apnea, and 13 had been using continuous positive airway pressure. For the diagnosis of sleep apnea, 1,318 participants (33.0%) responded that polysomnography was necessary. For sleep apnea treatment, 1,954 (48.9%) participants responded that lifestyle modification was the treatment of choice, while 1,036 (25.9%) chose continuous positive pressure. @*Conclusions@#Although one-fifth were at high risk for sleep apnea, this disorder is still underestimated. Therefore, publicity and support are needed to improve public awareness of sleep apnea.
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Objectives@#Clinicians often depend on the results of the the multiple sleep latency test (MSLT) for diagnosing narcolepsy, but the diagnosis can be confusing when there is a co-existence of obstructive sleep apnea (OSA). This study is aimed to address the diagnostic tendency and the strategies of treatment for narcolepsy and other hypersomnia in the grey zone. @*Methods@#We performed a web-based survey of Korean neurologists who were interested in narcolepsy and had experience with sleep studies. @*Results@#The results of this survey present their concerns according to the severity of comorbid OSA in analyzing the results of the MSLT. @*Conclusions@#This study also might help by providing the opinions of experienced Korean neurologists for the assessment and management of excessive daytime sleepiness.
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Background@#Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer. @*Methods@#Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data. @*Results@#Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis. @*Conclusion@#Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.
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Background@#Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease. @*Methods@#Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy. @*Results@#The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months. @*Conclusion@#Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.
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Thyroid hormones have an important physiological role in maintaining adult bone structure and strength. Therefore, thyroid dysfunction is inevitably associated with various degrees of skeletal consequences. Endogenous overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, resulting in osteoporosis and an increased risk of fractures. Hyperthyroidism induced by thyroid stimulating hormone suppression therapy in patients with differentiated thyroid cancer also has emerged as a contributing factor to osteoporosis and fragility fractures. While, there is lack of evidence that hypothyroidism negatively affects bone health. Although there is growing clinical evidence of the importance of bone health in hyperthyroidism, clinical guidelines on how to evaluate and manage bone health in these diseases have not yet been published worldwide. The Task Force from the Korean Thyroid Association Committee of Clinical Practice Guideline has developed this position statement for the evaluation and management of bone health in patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid stimulating hormone suppression therapyassociated hyperthyroidism in patients with differentiated thyroid cancer.
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Obstructive sleep apnea (OSA) is known to be associated with various health concerns, including sleepiness, fatigue, cognitive dysfunction, diminished quality of life, hypertension, cardiovascular diseases, and stroke. OSA-induced sleepiness at the wheel reduces vigilance and driving performance, which significantly increase the risk of motor vehicle accidents. Sleepiness-induced motor vehicle accidents are characterized by high morbidity and mortality. OSA is a well-established significant risk factor for drowsy driving-related motor vehicle accidents, which can be prevented through appropriate treatment. However, currently no clinical guidelines or regulations are available for evaluation or management of the risk of motor vehicle accidents in patients with OSA in Korea. In this review, we discuss the risk of motor vehicle accidents in patients with OSA, the effects of positive airway pressure therapy as a preventive measure to reduce this risk, and the published recommendations for OSA in other countries with regard to fitness to drive. We propose recommendations for screening, evaluation, and treatment of OSA with regard to the risk of motor vehicle accidents, which would serve as useful practical guidelines for sleep specialists in clinical practice. Further research is warranted to establish optimal strategies for effective improvements in OSA-related traffic safety.
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Narcolepsy is a chronic sleep disorder characterized by irresistible sleep attacks, hypersomnolence, cataplexy (sudden loss of muscle tone provoked by emotion), and sleep paralysis. Individuals with narcolepsy are at a high risk of experiencing sleepiness while driving leading to road traffic accidents. To prevent such accidents, some countries have regulations for commercial and noncommercial drivers with narcolepsy. Evaluating sleepiness is essential. Therefore, several subjective reports and objective tests were used to predict the possibility of car crashes or near-misses. Brain stimulants are effective in treating narcolepsy and can reduce daytime sleepiness in these patients. However, no guideline has been established for the driving safety of patients with narcolepsy in Korea. The Korean Sleep Research Society has prepared this proposal for preventing motor vehicle accidents caused by drowsy driving in patients with narcolepsy.
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Background@#The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules. @*Methods@#Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled. @*Results@#Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change. @*Conclusion@#K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.
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Background@#In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015. @*Methods@#BMD was classified as normal (T-score ≥–1.0 standard deviation [SD]), osteopenia (T-score –2.5 SD), and osteoporosis (T score ≤–2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD. @*Results@#Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD. @*Conclusion@#Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.
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Methods@#Data on demographic characteristics and medical comorbidities of patients who underwent PLF with subsequent readmission were obtained from the HCUP-NRD. The perioperative characteristics that were significantly different between patients readmitted with and without an active diagnosis of IBO were identified with bivariate analysis for both 30-day and 90-day readmissions. The significant characteristics were then included in a multivariate analysis to identify those that were independently associated with 30- day and 90-day readmissions. @*Results@#Drug abuse (odds ratio [OR], 4.00), uncomplicated diabetes (OR, 2.06), having Medicare insurance (OR, 1.65), age 55–64 years (OR, 2.42), age 65–79 years (OR, 2.77), and age >80 years (OR, 3.87) were significant risk factors for 30-day readmission attributable to IBO after a PLF procedure. @*Conclusions@#Of the several preoperative risk factors identified for readmission with IBO after PLF surgery, drug abuse had the strongest association and was likely to be the most clinically relevant factor. Physicians and care teams should understand the risks of opioid-based pain management regimens, attempt to manage pain with a multimodal approach, and minimize the opioid use.
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Although genetic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder, cases of genetic CJD with E200K mutation are being increasingly reported in Korea. However, the clinical features and course of genetic CJD with E200K mutation in Korea remain unclear. We describe the clinical features and course of genetic CJD with E200K mutation in a patient who initially presented with rapid progressive memory impairment and myoclonus.
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Driving is a complicated process that demands coordination between a range of neurocognitive functions, including attention, visuo-perception, and appropriate judgment, as well as sensory and motor responses. Therefore, several factors may reduce the driving performance of an individual, such as sleepiness, distraction, overspeeding, alcohol consumption, and sedative drugs, all of which increase the hazard of motor vehicle accidents. Among them, drowsy driving is a major cause of traffic accidents, leading to more serious injuries as compared to other causes of major traffic accidents. Although sleep disorders have been highly associated among drowsy drivers, they are often untreated and unrecognized as a disease. In particular, obstructive sleep apnea and narcolepsy are some sleep disorders that are highly related to traffic accidents. Insomnia, which can cause inadequate sleep duration and promote sedative effects from sleeping pills, may also cause traffic accidents. These conditions are especially applicable to commercial bus or truck drivers, nocturnal workers, and shift workers, who are highly vulnerable to drowsy driving. Therefore, assertive screening and management of sleep disorders are necessary in general private drivers and relevant occupational drivers.
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We report two rare cases treated with coiling after rapid regrowth (within a month) of an aneurysm remnant on the middle cerebral artery (MCA) trunk after incomplete surgical clipping. The first case, a 47-year-old man with subarachonoid hemorrhage (SAH) (Hunt-Hess grade II, Fisher grade III) underwent clipping of a ruptured saccular aneurysm with a wide neck on the right early frontal branch arising from the MCA trunk. Incomplete clipping with a 1 mm sized remnant neck was performed to avoid sacrificing the lenticulostriate artery. In a follow-up cerebral angiogram on postoperative day 30, a rapid regrowth of the aneurysm remnant was observed, and on that day, complete obliteration was obtained by rescue endovascular treatment. The second case, a 48-year-old healthy woman with SAH (Hunt-Hess grade II, Fisher grade III) underwent clipping of an anteroposteriorly projecting bilobulated aneurysm on the left M1. Incomplete clipping with a minimal remnant neck was performed. In follow-up digital subtraction angiogram on postoperative day 30, a rapid regrowth of an aneurysm remnant involving only a part of the initial aneurysm near the neck was observed, and on that day, complete obliteration was obtained by rescue coiling. These patients were both discharged without any neurological deficits.
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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@#This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC). @*Methods@#A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression. @*Results@#Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels. @*Conclusion@#Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.