ABSTRACT
Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.
ABSTRACT
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
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Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.
Subject(s)
Humans , Optogenetics , Brain/physiology , Microglia , Chronic Pain/therapy , Neurons/physiologyABSTRACT
The survival rate of children admitted in the neonatal intensive care unit (NICU) after birth is on the increase; hence, proper evaluation and care of their neurodevelopment has become an important issue. Neurodevelopmental assessments of individual domains regarding motor, language, cognition, and sensory perception are crucial in planning prompt interventions for neonates requiring immediate support and rehabilitation treatment. These assessments are essential for identifying areas of weakness and designing targeted interventions to improve future functional outcomes and the quality of lives for both the infants and their families. However, initial stratification of risk to select those who are in danger of neurodevelopmental disorders is also important in terms of cost-effectiveness. Efficient and robust functional evaluations to recognize early signs of developmental disorders will help NICU graduates receive interventions and enhance functional capabilities if needed. Several age-dependent, domain-specific neurodevelopmental assessment tools are available; therefore, this review summarizes the characteristics of these tools and aims to develop multidimensional, standardized, and regular follow-up plans for NICU graduates in Korea.
ABSTRACT
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.
ABSTRACT
Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.
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Purpose@#: Intensive care unit (ICU) diaries have been implemented across the international ICU community. This study aimed to comprehend the meaning and nature of the lived experience of patients’ families using the ICU diary in Korea. @*Methods@#: This qualitative study adopted van Manen’s hermeneutic phenomenology. The participants comprised eight women and two men who were the family members of patients in the ICU for more than three days. Data were collected using in-depth interviews and observation from July 2018 to January 2019. @*Results@#: Patients’ families who experienced the ICU diary recognized it with six beings according to time: a good idea, forgotten stuff, burdensome work, touching service, my stuff, and a thing in the memory. The ICU diary had three essential meanings for the families: communication, solace and hope, and a record of life. These findings were rearranged according to van Manen’s fundamental existential, and the lived things and lived others were remarkably confirmed. @*Conclusion@#: Patients’ families experienced various ICU diary forms over time and recognized an ICU diary as a means of communication. Therefore, the ICU diary is expected to be used as an intervention between families and healthcare providers in the ICU to support mutual communication.
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Thyroid hormone plays an important role in the process of implantation of a fertilized egg in the endometrium, as well as in the division and development of the fertilized egg. In addition, maternal thyroid hormone is essential for the formation and development of the fetal brain, nervous system, and bones. Therefore, when maternal thyroid hormone is insufficient, complications such as miscarriage, stillbirth, low birth weight and preeclampsia increase. Guidelines for the diagnosis and treatment of thyroid dysfunction during pregnancy were established and published by the American Endocrine Society, the American Thyroid Association, and the European Thyroid Society. The Korean Thyroid Society also published recommendations for diagnosis and treatment of thyroid disease during pregnancy and postpartum in 2014. However, since the revised guidelines of the American Thyroid Association were published in 2017, many studies, including large-scale randomized controlled trials, have been published in relation to thyroid and pregnancy, and the need to revise the existing recommendations has emerged in Korea.The main revisions of this recommendation are changes in the normal range of TSH during pregnancy, detailed description of treatment policies according to pregnant women’s autoantibodies and thyroid function status. Also, a description of the effect of thyroid autoantibodies on assisted reproductive procedures has been added.
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Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.
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Thyroid nodules are a prevalent condition that can be detected through palpation or ultrasound. However, a small fraction of these nodules can be cancerous, and even benign nodules can cause symptoms if they grow and compress surrounding tissue. As such, it is important to monitor thyroid nodules and determine appropriate treatment options. In recent years, there has been a shift towards enhancing diagnostic accuracy and less aggressive treatment options. As a result, there is a growing need for the development of appropriate recommendations for their clinical application to ensure optimal patient outcomes. The present clinical practice guideline was developed by extracting the nodule section from the prior version of guidelines and updating it to fit the Korean circumstances. Task force members reviewed relevant studies selected after electronic database searching, and the recommendations are provided with a level of recommendation for each section. The revised guideline includes recommendations for thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, the role of pathological and molecular marker tests in diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major changes in this revision are the definition of high-risk groups for thyroid cancer screening, the application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), the addition of the role of core needle biopsy and molecular marker tests, the application of active surveillance in low-risk papillary thyroid microcarcinoma, and updated indications for non-surgical treatment of benign thyroid nodules. These evidence-based recommendations are expected to assist in clinical decision-making for thyroid nodule management, ensuring that patients receive the most appropriate and effective treatment options.
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Purpose@#The purpose of this study was to validate the Edmonson psychiatric fall risk assessment tool (EPFRAT) for psychiatric inpatients. @*Methods@#Data from retrospective study were collected from 670 adult inpatients in two departments of mental health medicine of a tertiary general hospital by reviewing their electronic medical records. There were 41 patients who experienced falls and 629 patients who did not experience falls during the period from January to December 2019. Data were analyzed by sensitivity, specificity, positive predictive value, negative predictive value, and a receiver-operating characteristic curve (ROC) for validity assessment using the IBM SPSS/WIN 26.0 program. @*Results@#Factors affecting falls were the participant’s age, guardian’s residence, high-risk determination at the time of admission, and comorbidity. At the 85 points where the point of sum of the sensitivity and specificity was largest, the sensitivity, specificity, positive predictive value, and negative predictive value of EPFRAT were 92.7%, 79.7%, 22.9%, and 99.4%, respectively. The area under the ROC to assess the overall validity of the tool was .92 (95% CI 0.89~0.94). @*Conclusion@#The EPFRAT was proved to be valid and reasonable for predicting falls in psychiatric inpatients. Based on the results of this study, it could be used for the assessment of high-risk patients for falls in psychiatric units.
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Objective@#To investigate the effect of sensory-based feeding treatment for toddlers with food refusal compared with only providing nutrition education. @*Methods@#Thirty-two toddlers with food refusal were randomly assigned to an intervention group or the control group. Toddlers in the intervention group received the sensory-based feeding intervention and the duration was for 1 hour for 5 days per week for 4 weeks, and then 1 hour, once a week for 8 weeks. Subjects in both the intervention and control groups received nutritional education once every 4 weeks for 12 weeks. The participants were evaluated at their entry into the study and 12 weeks later based on height, weight, behavior at mealtime using the Behavioral Pediatrics Feeding Assessment Scale (BPFAS), and sensory processing ability using the Infant/Toddler Sensory Profile. @*Results@#Sixteen toddlers were included in each group. Two subjects in the intervention group and four toddlers in the control group were excluded from the final analysis. Significant improvements in child or parent subscales of the BPFAS were observed in the intervention group. In contrast, there were no significant improvements in any BPFAS scores in the control group. @*Conclusion@#Sensory-based feeding intervention was effective for improving mealtime behavior in toddlers with food refusal. Therefore, a sensory-based feeding intervention could be considered as an intervention approach to address feeding disorders in toddlers.
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Purpose@#: This study aimed to identify the incidence of peripheral cyanosis and the characteristics and clinical results of patients with therapeutic hypothermia after a cardiac arrest. @*Methods@#: Data were collected from April to June 2021 via the electrical medical records of 95 patients with therapeutic hypothermia for 72 hours after a cardiac arrest admitted to an acute care unit at a tertiary hospital between January 1, 2016, and December 31, 2019. The data were analyzed using descriptive statistics and a t-test, Mann–Whitney U test, Chi-squared test, Fisher’s exact test, and logistic regression using SPSS/WIN. @*Results@#: The incidence of peripheral cyanosis was 20%. In the peripheral cyanosis group, peripheral vascular disease, fibrinogen, vasopressor, infection, disseminated intravascular coagulation, acute physiology, chronic health evaluation II score on the second hospital day, nursing intervention, and mortality on the seventh hospital day were higher. The level of fibrinogen and use of vasopressors affected the occurrence of peripheral cyanosis. @*Conclusion@#: Considering the influencing variables, careful observation is necessary for patients with high fibrinogen levels and vasopressor use. These results provide basic data to recognize the need for nursing intervention for peripheral cyanosis and encourage nurses to deliver them during therapeutic hypothermia.
ABSTRACT
Graves’ disease is the most common cause of hyperthyroidism which is caused by stimulating autoantibodies against thyroid-stimulating hormone receptor. There is no etiology-specific treatment for Graves’ disease.Current Concepts: Graves’ disease can be treated with antithyroid drugs (ATDs), radioactive iodine, or thyroidectomy. ATDs are the most preferred first-line therapy, because they do not cause either permanent hypothyroidism or exacerbation of orbitopathy, despite low remission rate. ATDs have serious adverse reactions including agranulocytosis and fulminant hepatic necrosis requiring liver transplantation. Methimazole (MMI) is recommended in every patient starting ATD therapy, except during the first trimester of pregnancy and in cases of thyroid storm, because of relatively lower incidence and severity of serious adverse reactions compared with propylthiouracil. Treatment should be continued for 12 to 18 months, then discontinued if the levels of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies are normalized. In cases of relapse of hyperthyroidism, radioactive iodine or thyroidectomy can be recommended for definitive therapy; however, recent studies support longer-term maintenance of low dose MMI as a favorable alternative therapy. All ATDs may induce congenital anomalies when exposed during early pregnancy. Every female patient of reproductive age should be advised to postpone pregnancy until their thyroid function is maintained within normal range and to stop ATDs when pregnancy is confirmed to avoid the risk of congenital anomalies.Discussion and Conclusion: Longer-term low dose MMI therapy can be a good choice for Graves’ hyperthyroidism with relapse. Before pregnancy, hyperthyroidism should be controlled to stop ATDs during pregnancy.
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Ticks can transmit pathogenic bacteria, protozoa, and viruses to humans and animals. In this study, we investigated the microbiomes of Haemaphysalis longicornis according to sex and life stages. The Shannon index was significantly higher for nymphs than adult ticks. Principal coordinates analysis showed that the microbiome composition of female adult and male adult ticks were different. Notably, Coxiella-like bacterium (AB001519), known as a tick symbiont, was found in all nymphs and female adult ticks, but only one out of 4 male adult ticks had Coxiella-like bacterium (AB001519). In addition, Rickettsia rickettsii, Coxiella burnetii, and Anaplasma bovis were detected in this study.
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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@#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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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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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.
ABSTRACT
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.