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

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

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

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

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

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

BACKGROUND AND OBJECTIVES: The extent of weight gain and its association with clinical factors in patients undergoing radioiodine therapy for differentiated thyroid cancer remain unclear. We analyzed clinical factors related to sustained weight gain after serum thyroid-stimulating hormone (TSH) stimulation for radioiodine (I-131) therapy. MATERIALS AND METHODS: The study population included 301 adult patients who underwent total thyroidectomy followed by radioiodine therapy and visited the thyroid clinic regularly. Group 1 received a single radioiodine therapy treatment, while group 2 received multiple radioiodine treatment. Data on transient weight gain, defined as weight gain that resolved (±5%) within 1 year after radioiodine therapy, were collected from medical records. Sustained weight gain was defined as body mass index after treatment (BMI(post)) - BMI before treatment (BMI(pre)) ≥2 kg/m2 more than 1 year following radioiodine therapy. Subjective symptoms were scored by questionnaire. Logistic regression analysis was performed using various clinical and laboratory factors to identify risk factors associated with sustained weight gain. RESULTS: Two hundred and fifty-nine (86%) patients showed transient weight gain and 23 (8%) patients showed sustained weight gain. TSH at therapy and T4-on TSH differed significantly in all patients and in the patients in group 1 with sustained weight gain. The proportion of patients with basal BMI≥25 kg/m2 in group 1 with sustained weight gain also differed significantly. Univariate analysis revealed that high serum levels of TSH at therapy (≥100 µIU/mL) and hypercholesterolemia were associated with sustained weight gain in group 1. Multivariate analysis showed that TSH at therapy levels ≥100 µIU/mL was associated with sustained weight gain in group 1. Of 283 patients remaining after excluding those with insufficient TSH suppression during follow-up, T4-on TSH levels were lower in the sustained weight gain group compared to those without sustained weight gain. TSH at therapy levels ≥100 µIU/mL were significantly associated with sustained weight gain in multivariate analysis. CONCLUSION: Most patients (86%) had transient weight gain after TSH at therapy, while 8% of patients showed sustained weight gain. Univariate and multivariate analysis revealed relatively high TSH levels (≥100 µIU/mL) to be a risk factor for patients that received a single dose of radioiodine therapy. Insufficient T4 dose was not associated with sustained weight gain.
Adult ; Body Mass Index ; Follow-Up Studies ; Humans ; Hypercholesterolemia ; Logistic Models ; Medical Records ; Multivariate Analysis ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin* ; Weight Gain*

BACKGROUND: Most cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH. METHODS: A total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced. RESULTS: The mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH. CONCLUSIONS: The mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.
Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Congenital Hypothyroidism/epidemiology/*genetics/pathology ; Exons ; Female ; Genetic Association Studies ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; NADPH Oxidase/*genetics ; Polymorphism, Single Nucleotide ; Republic of Korea/epidemiology ; Sequence Analysis, DNA ; Thyrotropin/blood

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.
Female ; Healthy Volunteers ; Humans ; Hypothyroidism ; Iodine ; Male ; Metabolism ; Selenium* ; Spectrum Analysis ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Nodule ; Thyrotropin