• Genomics & Informatics
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• v.19 no.3
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• pp.29.1-29.10
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• 2021

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H₂O₂. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, K_d of wild-type vs. mutant: 7.2E^-12 vs. 7.0E^-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.624-633
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• 2005

Purpose : This study analyzed the expression of HLA-DR and DQ genotypes and anti-thyroid autoantibodies[anti-thyroid peroxidase(TPO) and anti-thyroglobulin(TG) antibodies] in Korean patients with type 1 diabetes(T1DM) to investigate the susceptible HLA alleles to T1DM in Korea and the prevalence of thyroid autoantibodies and their significance for the development of thyroid disorders. Methods : A total of 59 Korean patients with type 1 diabetes[26 males, median age 13.7 years(range 5.7-29.9 years), diabetes duration 7.6 years(-1.7-22.5 years)] were enrolled in this study, and 200 healthy Koreans without a family history of diabetes were selected as a normal control for the comparison of HLA genotypes. Seventeen patients with anti-TPO or anti-TG were followed [median duration 3.96 years(1 day-10.7 years)] with measurement of anti-TPO, anti-TG, $T_3$, $T_4$ or free $T_4$, TSH levels and physical examinations. HLA-DR and DQ genotyping were done by PCR-SSO, PCR-SSCP, PCR-RFLP and PCR-SSP methods. Results : HLA analysis showed higher frequencies of HLA-DRB1*0301, *090102 and DQB1*0201, *030302 alleles, DRB1*0301/*090102, *090102/*090102 and DQB1 *0201/*030302, *030302/*030302, *0201/ *0302 genotypes in T1DM patients compared to controls(Pc<0.05). Fifteen(25.4 percent) had anti-TPO antibody, 12(20.3 percent) had anti-TG, 17(28.8 percent) had either autoantibody and 10(16.9 percent) had both autoantibodies. No clinical or subclinical hypothyroidism developed during follow-up after the first detection of anti-thyroid autoantibody. There was no significant correlation between thyroid autoimmunity and gender, onset age of T1DM, and diabetes duration, respectively(P>0.05). Conclusion : We thought this unique HLA-DR, DQ allele distribution might be an important factor for the low incidence of T1DM in Korea. And a high prevalence of thyroid autoantibodies in these populations suggests examinations of thyroid antibodies should be performed regularly. Optimal age for the initial screening and the frequency of re-screening for associated thyroid autoimmune diseases in T1DM remains to be determined through prospective follow-up.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.411-420
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• 2009

Purpose: The aim of this study was to investigate the usefulness of $^{18}F$-FDG PET/CT with neck ultrasonography (neck US) in patients with recurrent, papillary thyroid cancer. Material and methods: This retrospective study (December 2006 to April 2008) enrolled sixty-one patients (ninety-one lesions) who underwent high-dose $^{131}I$-ablation therapy after total thyroidectomy, and evaluated recurred papillary thyroid cancer. All lesions were confirmed by histopathology and compared histopathologic findings to PET, PET/CT, and neck US findings. Results: In sixty-one patients (57 women, 4 men; age range, 24-81 years, mean 49 years; 61 papillary carcinomas), the sensitivity, specificity, accuracy of $^{18}F$-FDG PET/CT was 87.2%, 64.0%, 78.1% on a patient basis and 92.3%, 66.7%, 80.9% on a lesion basis, respectively. The sensitivity, specificity, accuracy of $^{18}F$-FDG PET was 71.8% (p=0.03), 59.0% (p=1.00), 67.2% (p=0.03) on a patient basis and 78.8% (p<0.01), 64.1% (p=1.00), 72.5% (p=0.02) on a lesion basis, respectively. The sensitivity, specificity, accuracy of neck US was 71.1% (p=0.07), 52.2% (p=0.75), 63.9% (p=0.05) on a patient basis and 71.2% (p<0.01), 61.5% (p=1.00), 67.0% (p=0.06) on a lesion basis, respectively. Combined $^{18}F$-FDG PET/CT with neck US improved the sensitivity, specificity, accuracy to 94.7% (p=0.50), 82.6% (p=0.13), 90.2% (p=0.03) on a patient basis and 96.2% (p=0.50), 89.7% (p<0.01), 93.4% (p<0.01) on a lesion basis, respectively. Conclusion: $^{18}F$-FDG PET/CT demonstrated significantly higher sensitivity than neck US for the detection of recurred papillary thyroid cancer lesions. Furthermore, combined $^{18}F$-FDG PET/CT with neck US showed more improved sensitivity, specificity, accuracy for diagnosis of recurrent papillary thyroid cancer.

• The Korean Journal of Nuclear Medicine Technology
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• v.26 no.1
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• pp.42-46
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• 2022

Purpose In the meantime, there have been not many samples that require dilution, and it has been difficult for the examiner to set an appropriate dilution multiple for RIA test item and report the results. Accordingly, it was judged that it was necessary to set the maximum dilution multiple for each test and to verify the upper limit of the clinical reportable range. Therefore, in this study, the maximum dilution multiple for each RIA test was set and the upper limit of the clinical reportable range was verified accordingly Materials and Methods Among all RIA tests conducted at Asan Medical Center, the study treated on 30 types of tests which also conduct the dilution test. Data from March to July 2021 were collected and analyzed. The study was conducted on samples subjected to serial dilutions such as X2, X4 or X10, X10², X10³, X10⁴, X10⁵. Results Among a total of 30 test types, 18 test types have more than 5 N values in the tolerance range of 80~120%. As a result of the verification of maximum dilution multiples, the test set to 10⁴ is 𝛼-fetoprotein and thyroglobulin, and the test set to 10³ is CA-125, CEA, and 𝛽-hCG, and the test set to 10² is Free PSA, PSA, CA15-3, SCC, Ferritin, PTH, Cortisol, and Calcitonin. Tests set to 10 include three categories: 𝛽2-Microglobulin, C-peptide, and Testosterone. Conclusion It is expected that it will contribute to improving the quality of nuclear medicine blood tests as the results of dilution experiments can be reported quickly and accurately through the verification of the clinical reportable range.

• The Korean Journal of Nuclear Medicine Technology
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• v.26 no.2
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• pp.43-47
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• 2022

Purpose Radioimmunoassay implement quality control by systematizing the internal quality control system for quality assurance of test results. This study aims to contribute to the quality assurance of radioimmunoassay results and to implement systematic quality control by measuring the average CV of internal quality control and external quality control by plenty of institutions for reference when setting the laboratory's own acceptable range. Materials and Methods We measured the average CV of internal quality control and the bounce rate of more than 10.0% for a total of 42 items from October 2020 to December 2021. According to the CV result, we classified and compared the upper group (5.0% or less), the middle group (5.0~10.0%) and the lower group (10.0% or more). The bounce rate of 10.0% or more was compared by classifying the item of five or more institutions into tumor markers, thyroid hormones and other hormones. The average CV was measured by the overall average and standard deviation of the external quality control results for 28 items from the first quarter to the fourth quarter of 2021. In addition, the average CV was measured by the overall average and standard deviation of the proficiency results between institutions for 13 items in the first half and the second half of 2021. The average CV of internal quality control and external quality control was compared by item so we compared and analyzed the items that implement well to quality control and the items that require attention to quality control. Results As a result of measuring the precision average of internal quality control for 42 items of six institutions, the top group (5.0% or less) are Ferritin, HGH, SHBG, and 25-OH-VitD, while the bottom group (≤10.0%) are cortisol, ATA, AMA, renin, and estradiol. When comparing more than 10.0% bounce rate of CV for tumor markers, CA-125 (6.7%), CA-19-9 (9.8%) implemented well, while SCC-Ag (24.3%), CA-15-3 (26.7%) were among the items that require attention to control. As a result of comparing the bounce rate of more than 10.0% of CV for thyroid hormones examination, free T4 (2.1%), T3 (9.3%) showed excellent performance and AMA (39.6%), ATA (51.6%) required attention to control. When comparing the bounce rate of 10.0% or more of CV for other hormones, IGF-1 (8.8%), FSH (9.1%), prolactin (9.2%) showed excellent performance, however estradiol (37.3%), testosterone (37.7%), cortisol (44.4%) required attention to control. As a result of measuring the average CV of the whole institutions participating at external quality control for 28 items, HGH and SCC-Ag were included in the top group (≤10.0%), however ATA, estradiol, TSI, and thyroglobulin included in bottom group (≥30.0%). Conclusion As a result of evaluating 42 items of six institutions, the average CV was 3.7~12.2% showing a 3.3 times difference between the upper group and the lower group. Cortisol, ATA, AMA, Renin and estradiol tests with high CV will require continuous improvement activities to improve precision. In addition, we measured and compared the overall average CV of the internal quality control, the external quality control and the proficiency between institutions participating of six institutions for 41 items excluding HBs-Ab. As a result, ATA, AMA, Renin and estradiol belong to the same subgroup so we require attention to control and consider setting a higher acceptable range. It is recommended to set and control the acceptable range standard of internal quality control CV in consideration of many things in the laboratory due to the different reagents and instruments, and the results vary depending on the test's proficiency and quality control materials. It is thought that the accuracy and reliability of radioimmunoassay results can be improved if systematic quality control is implemented based on the set acceptable range.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.125-129
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• 2016

Background: Patients with differentiated thyroid cancers (DTC) who receive radioactive iodine-131 (RAI) are released from isolation when their dose rate is below the regulatory requirements. The purpose of this study was establish predicting factors for early release from the isolation facility after RAI administration in patients with DTC. Materials and Methods: This was a prospective study which included 96 (58 females and 38 males) patients with DTC who had received RAI from April 2013 till August 2015. The study was duly approved by the ethical committee of the institute. Patients who had complete information of primary tumor size (PTS), serum TSH, stimulated thyroglobulin level [sTg] with antibodies (IU/ml) at the time of RAI treatment were included. All had a normal serum creatinine level. To attain lower effective half-life good hydration and administration of soft laxative were ensured. Dose rate was measured (immediately, 24 h and 36 h) at 1 meter distance from anterior mid trunk and a dose rate <$50{\mu}Sv/h$ was considered as the releasing criterion. At 24 h 50 patients were released while the remaining 46 patients were released at 36 h. A post-ablative whole body scan (PA-WBIS) was performed 5-8 days after RAI ablation in all patients. Results: Patients released after 24 h were significantly younger, had smaller lesions with higher proportion of papillary cancer, lower sTg, lower sTg/TSH ratio and had received a lower dose of RAI as comapred to those who were discharged after 36 h. Serum TSH and gender were not found to have any significant correlation between two cohorts. ROC and multivariate analysis have shown age ${\leq}37years$, PTS ${\leq}3.8cm$, $RAI{\leq}150mCi$, $sTg{\leq}145ng/ml$ and $sTg/TSH{\leq}1.085$ as strong indepedent predictors for early release. Conclusions: We conclude that younger age (${\leq}37years$), smaller tumor size (${\leq}3.8cm$), lower RAI dose (${\leq}150mCi$), lower sTg (${\leq}145ng/ml$) and a lower sTg/TSH ratio (${\leq}1.085$) are significant independent predictors for release at 24 h after RAI treatment in DTC patients. Effective utilization of these factors could help the treating physicians to use limited number of internment facilities with higher throughput, lower cost and lower psychological stress to patients.

• Korean Journal of Head & Neck Oncology
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• v.15 no.1
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• pp.46-51
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• 1999

Background: Total thyroidectomy and postoperative radiodiodine ablation therapy in differentiated thyroid carcinomas enhance the reliability of serum thyroglobulin(Tg) levels and radioiodine scan in detecting recurrence or distant metastasis. There have been, however, some limitations in using these methods under certain conditions. Recently, several reports have indicated that thyroid peroxidase(TPO) could be used as an alternative tumor marker. We aimed to estimate the significance of serum TPO levels in differentiated thyroid carcinoma. Materials and Methods: Forty-eight patients who had undergone total thyroidectomy due to papillary thyroid carcinomas and who had been followed-up for at least 3 years were classified into two groups: 27 patients without any evidence of recurrence in group 1; and 20 patients with recurrence or distant metastasis in group 2. All patients were examined by radioiodine scans. Serum Tg, TSH, antithyroglobulin antibody, and TPO were measured and the relationships were statistically analyzed. The sensitivity and specificity of $^{131}I$ scan, serum Tg, and serum TPO were evaluated. Results: Serum Tg levels were $3.81{\pm}5.16ng/mL$ in group 1 and $147.02{\pm}193.75ng/mL$ in group 2. Only 2 patients in group 1 showed Tg levels exceeding 10ng/mL. In contrast, 4 patients in group 2 were under 10ng/mL. Serum antithyroglobulin antibody and TSH levels showed no statistical difference between the two groups. In group 1, 16 patients showed negative serum TPO results, and 4 patients in group 2 showed negative results. There was no correlation among serum Tg levels, antithyroglobulin antibody titers, and serum TPO levels in each group. In group 2, 4 patients with negative serum Tg levels showed positive TPO results and positive whole body scans. Two cases with false negative $^{131}I$ scans showed positive serum TPO and Tg results. In 4 cases showing false negative serum TPO levels, serum Tg levels and $^{131}I$ scans were positive. Conclusion: Serum Tg levels, radioiodine scans, and serum TPO levels can be clinically used as complementary methods in the diagnosis of recurrent or metastatic thyroid carcinomas. Serum TPO levels may be helpful when other methods fail to detect recurrences or distant metastasis in highly suspected patients.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.697-701
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• 2018

Background and Objectives The aim of this study was to evaluate surgical completeness in endoscopic total thyroidectomy with central neck dissection via unilateral axillo-breast approach (UABA) compared with bilateral axillo-breast (BABA) and open approach (OA) by means of the radioactive iodine uptake (RAIU) ratio and thyroglobulin (Tg) of remnant thyroid. Subjects and Method From July 2010 to March 2013, 82 patients who had underwent total thyroidectomy with central neck dissection and postoperative radioactive iodine (RAI) ablation for papillary thyroid carcinoma were enrolled. Of these patients, 27 patients underwent UABA, 24 patients BABA, and 31 patients OA. Clinicopathologic data, surgical outcome, stimulated Tg and RAIU ratio on the first postoperative RAI ablation scan were compared among 3 groups. Results Patients in the endoscopic surgery groups (UABA, BABA) were younger than those in the OA groups. Invasiveness such as operation time, postoperative pain, and drain amount in UABA was less than that in BABA and severer than that in OA. Other variables regarding clinicopathologic and surgical data were not significantly different. Stimulated Tg and RAIU ratio did not show significant differences among 3 groups (p=0.659 and p=0.664). Conclusion The completeness of UABA was comparable with that of BABA and OA. The UABA may be a safe option for patients who need endoscopic thyroidectomy for papillary thyroid carcinoma.

• The Korean Journal of Nuclear Medicine Technology
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• v.25 no.1
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• pp.41-43
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• 2021

Purpose In nuclear medicine blood tests, hemolysis samples are considered as inappropriate sample and are recommended not to be used for blood test. So, the lab are required to collect the blood again in the blood collection room However, The effect of hemolyzed samples on radioimmunoassay has not studied yet. This study was designed to evaluate effects of hemolysis on radioimmunoassay. Materials and Methods The kit manuals of 23 test items were reviewed to confirm whether hemolyzed samples were used. The subjects were 19 general applicants(male : 9, female : 13) and the samples were collected by each two SST tubes, one tube was obtained by centrifugation normally, and the other was obtained hemolyzed sample by centrifugation after external shock. It has been known that highly hemolyzed samples can affect the test results, so the test was performed using the severe hemolyzed sample. The test was performed for each test item using 23 normal serum and hemolysis serum, and SPSS19 program was used for statistical comparison of the test result. Results There was no significant difference between normal serum and hemolysis serum in 21 of 23 test items, but the results of insulin and C-peptide were significantly different(P<0.05). Conclusion It has been known that hemolysis in blood samples can affect the results of biochemical and hematological test, However, hemolysis effect is relatively low. Similarly, this study showed that hemolysis had not much effect on most of immunological radioimmunoassay except for some tests. Therefore, it is thought that the demand for re-collection due to hemolysis will be reduced in the laboratory, which will improve the work process of the laboratory.