• Genomics & Informatics
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• 제19권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6443-6447
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• 2014

Background: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). Materials and Methods: This retrospective study accrued 64 patients (23 male and 41 female; mean age of $40{\pm}14$ years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg <2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. Results: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ${\leq}14.5ng/ml$ was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg ${\leq}14.5ng/ml$ and 12/36 (33%) patients with baseline STg >14.5 ng/ml ((p value <0.05). Age >40 years, female gender, PTS >2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. Conclusions: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg < 2 ng/ml, a negative DWBIS and a negative US neck).

• Nuclear Medicine and Molecular Imaging
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• 제42권4호
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• pp.301-306
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• 2008

목적: 최근 조기건강검진에 대한 관심의 고조와 환경의 변화로 분화 갑상선암 진단 후 갑상선제거수술 및 고용량 방사성옥소 치료가 필요한 환자가 증가하고 있다. 저자들은 분화 갑상선암으로 진단 받고 갑상선제거 수술을 받은 환자에서 최초 고용량 방사성옥소 치료시 적절한 투여용량을 결정하는데 있어 병리적 병기소견이나 혈청 갑상선 글로불린치가 I-123 전신 스캔을 대신할 수 있는지를 알아보고자 하였다. 대상 및 방법: 갑상선 전절제술과 중앙 및 주변 림프절 제거술 후에 분화 갑상선암으로 진단 받은 환자 중에서 1차 고용량 방사성옥소 치료 전에 I-123 전신스캔을 시행한 58명(남:녀=13:45, 나이 $44.5{\pm}11.5$세)을 대상으로 하였다. 병리적 병기(T, N stage)는 2002 AJCC 기준에 따라 구분하였으나 나이에 따른 분류는 하지 않았다. 갑상선호르몬 중지 후 혈청 갑상선자극호르몬, 갑상선 글로불린과 갑상선글로불린항체 측정 및 I-123전신 및 국소영상(5 mCi 경구투여 후 24시간)을 얻었다. I-131 방사성옥소 치료는 I-123 스캔 결과에 따라 100 mCi에서 250 mCi 용량으로 시행하고, 치료용량과 병리적 병기, 혈청 갑상선글로불린치와의 관계를 비교하였다. 결과: I-131을 사용한 고용량 방사성옥소 치료는 5명(8.6%)에서 100 mCi, 43명(74.1%)에서 150 mCi, 6명(10.3%)에서 180 mCi. 3명(5.2%)에서 200 mCi, 1명(1.7%)에서 250 mCi로 각각 시행하였다. 병리적 병기에 따른 방사성옥소 치료용량은 stage I (n=9) $154{\pm}25\;mCi$, stage II (n=4), $175{\pm}50\;mCi$, Stage III (R=38); $149{\pm}21\;mCi$, Stage IV (n=7); $161{\pm}20\;mCi$을 보여 병리적 병기 증가와 치료용량 증가와는 유의한 상관성은 없었다. (p=0.169) 혈청 갑상선글로불린치에 따른 방사성옥소 치료용량은 2 ng/mL를 보인 군에서 $149{\pm}26 \;mCi$, 2 ng/mL이상 5 ng/mL 미만을 보인 군에서 $156{\pm}17\;mCi$, 5 ng/mL이상 10 ng/mL 미만을 보인 군에서 $156{\pm}13\;mCi$, 10 ng/mL이상 50 ng/mL 미만을 보인 군에서 $147{\pm}24 \;mCi$, 50 ng/mL이상을 보인 군에서 $175{\pm}42\;mCi$를 보여 혈청 갑상선글로불린치와 방사성옥소치료용량과는 유의한 상관성이 없었다. (p=0.252) 결론: 분화 갑상선암으로 갑상선 전절제술 후에 최초 고용량 방사성옥소 치료용량을 결정하는데 병리적 병기나 혈청 갑상선글로불린 수치가 I-123 전신 스캔을 대신하기는 어려울 것으로 생각된다.

• 대한두경부종양학회지
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• 제15권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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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.

• 대한한방내과학회지
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• 제27권3호
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• pp.653-663
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• 2006

Objective : Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder associated with autoantibodies to the TSH receptor. The clinical features of Graves' disease are goiter and hypermetabolic symptoms induced by excessive hormones. Antithyroid drug therapy is the first-line treatment for Graves' disease in Korea, Japan and European countries. Yet in spite of a long period and high-dose of treatment, it is hard to achieve remission because of adverse effects, frequent recurrence and resistance to antithyroid drugs. Recently, it has been reported that the abnormal thyroid hormone and clinical symptoms of Graves' disease were reduced by Ahnjeonbaekho-tang (AJBHT). Methods : To investigate the effectiveness and action mechanism of AJBHT, we studied the influence of AJBHT on FRTL-5 thyroid cell proliferation, DNA synthesis and expression of T4, TSH, cAMP, Tg and TPO mRNA. Results : AJBHT significantly inhibited the FRTL-5 cell proliferation, DNA synthesis, T4 synthesis, cAMP production and the expression of Tg mRNA in comparison with control and MMI. Conclusions : These results suggest that AJBHT may inhibit the cell proliferation and DNA synthesis by regulating the cAMP, and suppress the T4 synthesis by modulating Tg mRNA expression and cAMP synthesis, and that it may be useful agent for treating the goiter and hormone abnormality of Graves' disease.

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.624-633
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• 2005

목 적 : 본 연구는 한국인 제 1형 당뇨병 환자들에서 HLADR과 DQ 유전자형 및 갑상선 자가항체(항 TPO 자가항체와 항 thyroglobulin 자가항체)를 분석함으로써, 한국인 제 1형 당뇨병과 관련 있는 특정 HLA 유전자형을 알아보고자 하였고, 이들 제 1형 당뇨병 환자들에서의 갑상선 자가항체의 유병률, 갑상선 질환으로의 발현 및 이들 자가면역성 갑상선염과 HLA 유전자형과의 관련성을 알아보고자 하였다. 방 법 : 총 59명[남아 26명, 검사시 연령 13.7세(5.7-29.9세), 당뇨병 유병기간 7.6년(-1.7-22.5년)]의 제 1형 당뇨병 환자를 대상으로 하였고, 갑상선 질환의 병력 및 가족력이 없는 건강한 200명의 한국인의 HLA 유전자형을 대조군으로 하였다. 59명의 환자 중 갑상선 자가항체 양성인 17명은 중앙기간 3.96년(1일-10.7년) 동안 진찰 및 anti-TPO, anti-TG, $T_3$, $T_4$ 또는 free $T_4$, TSH 검사를 시행하면서 추적 관찰하였다. HLA-DR과 DQ의 유전자 분석은 PCR-SSO, PCR-SSCP, PCR-RFLP 및 PCR-SSP 방법을 이용하였다. 결 과 : 제 1형 당뇨병 환자들에서 대조군에서보다 HLADRB1*0301, *090102, DQB1*0201, *030302, DRB1*0301/*090102, DRB1*090102/*090102, DQB1*0201/*030302, *030302/*030302, *0201/*0302의 빈도가 높았다(Pc<0.05). 15명(25.4%)에서 TPO에 대한 자가항체 양성이었고, 12명(20.3%)에서 TG 자가항체 양성이었으며, 17명(28.8%)은 두 가지 항체 중 한 가지 이상의 항체를 갖고 있었다. 10명(16.9%)은 두 종류의 항체를 모두 갖고 있었다. 갑상선 항체 양성을 보인 이후부터의 추적기간 동안 갑상선기능저하증을 보인 경우는 없었다. 3명(5.1%)의 여아에서 당뇨병 진단 전 또는 후에 갑상선기능항진증이 진단(8.5세, 11세, 13.2세)되었다. 갑상선 자가항체의 유무 및 각각의 항체 종류에 따른 대상군간의 제 1형 당뇨병 진단연령, 갑상선 검사시 연령, 당뇨병 유병기간 및 성별의 차이는 보이지 않았다(P>0.05). 결 론 : 한국인에서는 HLA-DRB1*0301, *090102, DQB1*0201, *030302, DRB1*0301/*090102, *090102/*090102, DQB1*0201/*030302, *030302/*030302, *0201/*0302 등이 제 1형 당뇨병에 대한 감수성 인자였고, 코카시안과는 다른 HLA-DR 및 DQ의 분포가 한국인에서 제 1형 당뇨병의 발생률이 낮은 이유중의 하나를 차지하리라고 생각되었다. 한편, 제 1형 당뇨병 환자들에서 갑상선 자가항체 양성률은 28.8%였고, 이는 한국인 제 1형 당뇨병 환자에서도 갑상선 자가항체 검사가 규칙적으로 시행되어야 함을 시사한다고 하겠다. 한국인 제 1형 당뇨병 환자에서 자가면역성 갑상선 질환에 대한 선별검사 시작 시기와 횟수 등에 대해서는 이들 환자들의 장기적인 추적관찰을 통해 추후 좀더 연구가 필요하리라 생각된다.

• 핵의학기술
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• 제20권2호
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• pp.69-74
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• 2016

Insulin 83건을 검사 대상으로, 장비 WIZARD(PerkinElmer, USA)와 DREAM- G-10(Shinjin, KOREA)의 Graph Algorithm 중에 표준곡선과 신뢰성이 가장 높은 Excel의 추세선은 다항식 추세선이다. 다음으로 다항식 추세선식을 이용하여 표준농도 1개씩을 제외하여 표준농도의 회귀식에 미치는 영향을 비교한 결과 최고농도($315{\mu}IU/m{\ell}$)의 평균값이 표준물질 6개로 실시한 표준 회귀식을 이용한 평균값과 비교하여 49%나 평균값이 저하되었다. 단 낮은 농도에서는 영향이 미비하였다. 마지막으로 WIZARD의 Point to Point형식과 DREAM G-10의 Point to Point형식이 적합성이 높고, DREAM G-10(Point to Point)와 Excel 다항식 추세선이 적합성이 높으며, Excel 다항식 추세선과 DREAM G-10(2'nd order Polynomial)의 적합성이 높다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제30권1호
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• pp.42-44
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• 2019

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.

• 대한세포병리학회지
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• 제7권2호
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• pp.134-137
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• 1996

Monoclonal antibody(TCM-9) against human thyroid cancers have been studied by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody(TCM-9) that is known to have strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid does not bind to native or mature human thyroglobulin(Tg). We used to TCM-9 antibody by immunohistochemical staining on 5 follicular cancer, 2 follicular adenoma, 1 follicular neoplasm with suspicious invasion, 2 papillary cancer to ascertain being of help in differentiation between follicular carcinoma and adenoma. Reactivity of TCM-9 was observed in follicular carcinoma and papillary carcinoma but not observed in follicular adenoma. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.