BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
Lipid Metabolism/genetics* ; Mendelian Randomization Analysis ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Triiodothyronine

PURPOSE: This study aimed to investigate the prevalence of delayed thyroid dysfunction based on iodine disinfectant use and to analyze associated risk factors.METHODS: A retrospective study was conducted on late preterm infants admitted to the neonatal intensive care unit between January 2010 and June 2018, who underwent neonatal thyroid screening (NTS) and ≥2 thyroid function tests (TFTs). NTS was performed 3 days after birth, with at least two TFTs 1 week and 2 to 4 weeks after birth. To distinguish between normal and dysfunctional thyroid levels, we reviewed TFT results at 2 to 4 weeks and examined possible risk factors for the development of thyroid dysfunction.RESULTS: Of 295 late preterm infants, 262 were enrolled with a mean gestational age and birth weight of 34.8±0.7 weeks and 2,170±454 g, respectively. A total of 7.6% developed hyperthyrotropinemia at the age of 24.3±14.6 days (range, 12 to 69). The incidence of hyperthyrotropinemia during iodine use was approximately 12.6%, while that during discontinuation was 2.4% (P=0.002). Multivariate analysis revealed that small for gestational age (SGA), iodine disinfectant use, and abnormal NTS results were significant risk factors for delayed hyperthyrotropinemia (adjusted odds ratio [AOR]: 4.27, P=0.008; AOR: 8.24, P=0.003; and AOR: 7.80, P=0.002, respectively).CONCLUSION: Delayed hyperthyrotropinemia was prevalent in late preterm infants exposed to topical iodine and those identified as being SGA. Secondary TFTs should be considered 2 to 4 weeks after birth for this population at risk.
Birth Weight ; Congenital Hypothyroidism ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Premature ; Intensive Care, Neonatal ; Iodine ; Mass Screening ; Multivariate Analysis ; Odds Ratio ; Parturition ; Population Characteristics ; Prevalence ; Retrospective Studies ; Risk Factors ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.
Follow-Up Studies ; Humans ; Iodine ; Multivariate Analysis ; Sensitivity and Specificity ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Thyrotropin

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.
Autoantibodies ; Biochemistry ; Female ; Humans ; Immunoradiometric Assay ; Iodine ; Korea* ; Mothers ; Nutritional Status ; Pregnancy Outcome ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Pregnancy* ; Pregnant Women ; Reference Values ; Republic of Korea ; Spectrum Analysis ; Thyroid Gland* ; Thyroid Hormones* ; Thyrotropin ; Thyroxine

OBJECTIVE: Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. MATERIALS AND METHODS: Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. RESULTS: All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). CONCLUSION: Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.
Disease Progression ; Female ; Humans ; Hypothyroidism ; Male ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Sodium Pertechnetate Tc 99m ; Thyroid Diseases ; Thyroid Gland* ; Thyroiditis* ; Thyrotropin

Subclinical hyperthyroidism and subclinical hypothyroidism are characterized by abnormal thyroid stimulating hormone (TSH) with normal free thyroxine. Subclinical thyroid diseases, to date, have received less attention compared with other thyroid diseases since they are asymptomatic. This study aimed to verify the association between subclinical thyroid diseases and cardiovascular diseases (CVDs) risk score in the Korean population. This was a population-based cohort study using data collected from 3,722 subjects (aged ≥ 30 years) during the 6th Korea National Health and Nutrition Examination Survey (KNHANES VI; 2013–2015). Gender-specific Framingham risk scores were calculated to identify the association between subclinical thyroid diseases and 10-year CVD risk score. Complex survey, with consideration of sampling weight, was analyzed using generalized linear models after stratification by gender. The TSH reference range was between 0.61 and 6.91 mIU/L in this study. TSH showed a positive association with the 10-year CVD risk score only in the female population (P = 0.001). There were significant differences in the least squares means of 10-year CVD risk score by the effect of subclinical hypothyroidism compared with euthyroidism (normal group) in females, after adjusting for body mass index, white blood cell, and urine iodine (P = 0.006 and Bonferroni corrected P = 0.012). In conclusion, subclinical hypothyroidism is associated with increased 10-year CVD risk score in the female Korean population aged 30 years or more. Therefore, we recommend to clinically checkup major CVD risk factors in female patients with subclinical hypothyroidism aged 30 years or more.
Body Mass Index ; Cardiovascular Diseases* ; Cohort Studies ; Female ; Humans ; Hyperthyroidism ; Hypothyroidism ; Iodine ; Korea ; Least-Squares Analysis ; Leukocytes ; Linear Models ; Nutrition Surveys ; Reference Values ; Risk Factors ; Thyroid Diseases* ; Thyroid Gland* ; Thyrotropin ; Thyroxine

PURPOSE: The measurement of serum thyroglobulin (Tg) of papillary thyroid carcinoma patients, 12 months after total thyroidectomy and radioactive iodine (RAI) ablation following thyroxine hormone withdrawal (T4-off Tg) or recombinant human thyroid-stimulating hormone stimulation (rhTSH-Tg), is standard method for monitoring disease status. The aim of this study was to find predictive factors for detectable T4-off Tg during follow-up. METHODS: A retrospective review was conducted of 329 patients who underwent total thyroidectomy and RAI ablation between October 2008 and August 2012. Subjects were assigned to high (>1 ng/mL, n = 53) and low (≤1 ng/mL, n = 276) groups, based on T4-off Tg measured 12 months postoperatively. Demographic and clinicopathological characteristics at diagnosis and follow-up were compared between the 2 groups. RESULTS: The low and high T4-off Tg groups differed with respect to tumor size, preoperative Tg, ablative Tg, cervical lymph node metastasis, thyroglobulinemia out of proportion to results of diagnostic whole body scan, and American Thyroid Association 3-level stratification and restratification. Multivariate analysis confirmed that ablative Tg > 1.0 ng/mL (odds ratio [OR], 10.801; P = 0.001), more than 5 cervical lymph node metastasis (OR, 6.491; P = 0.003), and thyroglobulinemia out of proportion (OR, 9.221; P = 0.000) were risk factors. CONCLUSION: Ablative Tg >1.0 ng/mL, more than 5 cervical lymph node metastasis, and thyroglobulinemia out of proportion were independent factors for T4-off Tg >1 ng/mL 12 months postoperative. In low-risk patients without these risk factors, the possible omission of Tg measurements could be considered during follow-up.
Diagnosis ; Follow-Up Studies ; Humans ; Iodine* ; Lymph Nodes ; Methods ; Multivariate Analysis ; Neoplasm Metastasis ; Retrospective Studies ; Risk Factors* ; Thyroglobulin* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin ; Thyroxine ; Whole Body Imaging

BACKGROUND/AIMS: This study evaluated the relationship between thyroid nodules and metabolic syndrome (MS) and its components in apparently healthy Koreans. METHODS: We reviewed the records of 3,298 subjects with no noticeable symptoms who underwent thyroid ultrasound imaging as part of a routine check-up between July 2009 and June 2010; of these, 1,308 were excluded based upon predefined criteria. Among the remaining 1,990 patients, we examined the association between MS and its components and the incidence of thyroid nodules. RESULTS: Of the 1,990 subjects included in this study, 38.4% (n = 764) had thyroid nodules and 12.7% (n = 253) had MS. Female sex, older age, higher body mass index, larger waist circumference, higher glycated hemoglobin level, lower thyroid stimulating hormone level, and presence of MS were all closely related with the presence of thyroid nodules (all p < 0.05). Furthermore, the relevant number of MS components showed a positive linear correlation with the occurrence of thyroid nodules (p < 0.001). Evidence of MS alone was not independently associated with thyroid nodules after adjusting for sex and age in a multivariate binary logistic regression analysis; however, glycated hemoglobin for females and waist circumference for males, as well as both age and thyroid stimulating hormone for all patients, were identified as independent predictors for the existence of thyroid nodules (all p < 0.05). CONCLUSIONS: This study suggests a positive relationship between the components of MS and thyroid nodules in an ostensibly healthy Korean population. Our data support the idea that the recent increase in thyroid nodules is partly due to increases in both MS and obesity.
Adult ; Biomarkers/blood ; Body Mass Index ; Chi-Square Distribution ; Cross-Sectional Studies ; Diabetes Mellitus/diagnosis/epidemiology ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Incidence ; Linear Models ; Logistic Models ; Male ; Metabolic Syndrome X/blood/diagnosis/*epidemiology ; Middle Aged ; Multivariate Analysis ; Obesity/diagnosis/epidemiology ; Odds Ratio ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Thyroid Nodule/blood/diagnostic imaging/*epidemiology ; Thyrotropin/blood ; Waist Circumference

OBJECTIVE: To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. MATERIALS AND METHODS: This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors-such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels-were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. RESULTS: Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041-0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. CONCLUSION: Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.
Adult ; Aged ; Biopsy, Fine-Needle ; Family ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Retrospective Studies ; Risk Factors ; Sex Factors ; Thyroid Neoplasms/pathology/*ultrasonography ; Thyroid Nodule/pathology/*ultrasonography ; Thyrotropin/blood

BACKGROUND: The management of papillary thyroid carcinoma (PTC) in high-risk patients is well-standardized. However, this is not the case for low-risk patients. Filipinos show a high incidence of recurrence of thyroid cancer. Thus, the identification of risk factors for recurrence in this population could potentially identify individuals for whom radioactive iodine (RAI) therapy might be beneficial. METHODS: We reviewed the medical records of adult Filipinos with low-risk PTC who underwent near-total or total thyroidectomy at the University of the Philippines-Philippine General Hospital. Multivariate logistic regression analysis was used to determine risk factors for recurrence. RESULTS: Recurrence was documented in 51/145 of patients (35.17%) included in this study. Possible risk factors such as age, sex, family history, smoking history, tumor size, multifocality, prophylactic lymph node dissection, initial thyroglobulin (Tg) level, initial anti-thyroglobulin (anti-Tg) antibody concentration, suppression of thyroid stimulating hormone production, and RAI therapy were analyzed. Multivariate analysis revealed that a tumor diameter 2 to 4 cm (odds ratio [OR], 9.17; 95% confidence interval [CI], 1.62 to 51.88; P=0.012), a tumor diameter >4 cm (OR, 16.46; 95% CI, 1.14 to 237.31; P=0.04), and a family history of PTC (OR, 67.27; 95% CI, 2.03 to 2228.96; P=0.018) were significant predictors of recurrence. In addition, RAI therapy (OR, 0.026; 95% CI, 0.01 to 0.023; P≤0.005), an initial Tg level ≤2 ng/mL (OR, 0.049; 95% CI, 0.01 to 0.23; P≤0.005), and an anti-Tg antibody level ≤50 U/mL (OR, 0.087; 95% CI, 0.011 to 0.67; P=0.019) were significant protective factors. CONCLUSION: A tumor diameter ≥2 cm and a family history of PTC are significant predictors of recurrence. RAI therapy and low initial titers of Tg and anti-Tg antibody are significant protective factors against disease recurrence among low-risk PTC patients.
Adult ; Hospitals, General* ; Humans ; Incidence ; Iodine ; Logistic Models ; Lymph Node Excision ; Medical Records ; Multivariate Analysis ; Recurrence* ; Risk Factors* ; Smoke ; Smoking ; Thyroglobulin ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin