• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.21-26
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• 1988

Serum TBII measured by radioreceptor assay using $^{125}I-bovine$ TSH and porcine thyroid well membrane was checked before, 6 months and 12 months after initiation of thionamide regimens in 63 Graves' disease patients and was related with their remission state. 1) A significant difference (p < 0.01) in pre-treatment TBII was noted between the remitted [N = 45, TBII $40.9{\pm}18.2%$ $(mean{\pm}S.D)$] and the unremitted (N = 18, TBII $64.1{\pm}15.3%$) groups. 2) After 6 months of therapy, TBII were significantly decreased in both groups (to $20.2{\pm}10.3%$ and to $45.2{\pm}16.3%$, p<0.05 for each group) 3) At 12th month, TBII activities were not significantly decreased compared to the 6th month levels in both groups. 4) 3 of the 58 patients who were initially TBII positive (over 15%) converted negative. All the 3 belonged to the remitted group. 5) No significant differences were seen in initial and posttreatment TBII levels between propylthiouracil treated (N = 36) and methimazole treated (N = 27) cases. with above mentioned results, we observed that the TBII decreased significantly with 6 months of thionamide therapy and concluded that the pretreatment measurement of serum TBII may be clinically useful in predicting the response to thionamide regimen in the treatment of Graves' disease.

• The Korean Journal of Nuclear Medicine
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• v.20 no.2
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• pp.85-100
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• 1986

To evaluate the clinical and pathogenetic roles of TSH receptor antibodies in autoimmune thyroid diseases, TBII were measured by TSH-radioreceptor assay methods in 352 patients with Graves' disease, 108 patients with other thyroid diseases and 69 normal persons. The normal range of TBII activity was less than 15%. The frequencies of detectable TBII in 169 patients with untreated Graves' disease, 31 patients with hyperthyroidism under treatment and 70 patients with euthyrodism under treatment were 92.4%, 87.1% and 54.3% respectively. However 12 (21.8%) out of 55 patients who have been in remission more than one year after discontinuation of antithyroid drugs treatment had detectable TBII activities in their sera. In 196 patients with untreated Graves' disease, the frequency of TBII increased by increasing size of goiter and the frequency of proptosis was significantly high in patients whose TBII activities were more than 60%. TBII activities were roughly correlated with total $T_3,\;T_4$ and free $T_4$ index but low $\gamma^2$ value(less than 0.1). In 67 patients with Graves' disease who were positive TBII before antithyroid drugs treatment, TBII activities began to decrease from the third months and it was converted to negative in 35.8% of patients at 12 months after treatment. There were no significant differences of the declining and disappearing rates of TBII activities between high dose and conventional dose groups. TBII activities were significantly increased initially (2-4 months) and then began to decrease from 5-9 months after $^{131}I$ treatment. There were two groups, one whose TBII activities decreased gradually and the other did not change untill 12 months after subtotal thyroidectomy. Although preoperative clinical and laboratory findings of both groups were not different, TBII activities of non-decreasing group were significantly higher than those of decreasing group$(74.6{\pm}18.6%\;vs\;39.2{\pm}15.2%;\;P<0.01)$. Thirty three(55.9%) out of 59 patients with Graves' disease relapsed within 1 year after discontinuation of antithyroid drugs. The positive rate of TBII at the end of antithyroid drug treatment in relapse group(n=33) was significantly higher than those in remission group (n=26) (63.6% vs 23.1%; P < 0.05). The mean value of TBII activities at the end of antithyroid drug treatment in relapse group was significantly elevated $(29.7{\pm}21.4%\;vs\;14.7{\pm}11.1%,\;P<0.05)$. Positive predictive value of TBII for relapse was 77.8%, which was not different from those of TRH nonresponsiveness(78.6%). The frequencies of detectable TBII in 68 patients with Hashimoto's thyroiditis, 10 patients with painless thyroiditis and 5 patients subacute thyroiditis were 14.7%, 20% and 0%, respectively. However in 25 patients with primary nongoitrous myxedema, 11 patients(44%) showed TBII activities in their sera. 9 out of 11 patients who had TBII activities in their sera showed high TBII activities(more than 70% binding inhibition) and their IgG concentrations showing 50% binding inhibition of $^{125}I-bTSH$ to the TSH receptor were ranges of 0.1-2.6 mg/dl. One patient who had high titer of TBII in her serum delivered a hypothyroid baby due to transplacental transfer of maternal TBII. These findings suggested that 1) TSH receptor antibodies are closely related to a pathogenetic factor of Graves' hyperthyroidism and of some patients with primary non-goitrous myxedema, 2) measurement of TSH receptor antibodies is helpful in evaluating the clinical outcome of patients with Graves' disease during antithyroid drug treatment and in predicting the neonatal transient hypothyroidism of baby delivered from primary myxedema patients. 3) there are 2 or more different types of TSH receptor antibodies in autoimmune thyroid diseases including one which stimulates thyroid by binding to the TSH receptor and another which blocks adenylate cyclase stimulation by TSH.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.65-76
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• 1996

In order to evaluate the significance of thyrotropin-binding inhibiting immunoglobulin (TBII) in the patients with autoimmune thyroid diseases, the authors investigated 402 cases of Graves' disease and 230 cases of Hashimoto's thyroiditis comparing 30 cases of normal healthy adult at Kyung Pook University Hospital from February 1993 to August 1994. The TBII was tested by radioimmunoassay and assesed on the dynamic change with the disease course, thyroid functional parameters, and other thyroid autoantibodies : antithyroglobulin antibody (ATAb) and antimicrosomal antibody (AMAb) including thyroglobulin. The serum level of TBII was $40.82{\pm}21.651(mean{\pm}SD)%$ in hyperthyroid Graves' disease and $8.89{\pm}14.522%$ in Hashimoto's thyroiditis and both were significant different from normal control of which was $3.21{\pm}2.571%$. The frequency of abnormally increased TBII level was 92.2% in hyperthyroid Graves' disease, 46.7% in euthyroid Graves' disease or remission state of hyperthyroidism, and 23.9% in Hashimoto's thyroiditis. The serum levels of increased TBII in Graves' disease were positively correlated with RAIU, serum T3, T4, and FT4, but negatively correlated with serum TSH(each P<0.001). The TBII in Graves' disease had significant positive correlation with serum thyroglobulin and AMAb, but no significant correlation with ATAb. In the Hashimoto's thyroiditis, the serum levels of TBII were positively correlated with RAIU, serum T3, TSH and AMAb, but not significantly correlated with serum T4, FT4, thyroglobulin and ATAb. Therefore serum level of TBII seemed to be a useful mean of assessing the degree of hyperthyroidism in Graves' disease and correlated well with thyroidal stimulation. The serum level of TBII in Hashimoto's thyroiditis is meaningful for the degree of both functional abnormality reflecting either hyperfunction or hypofunction and the immune logic abnormality.

• The Korean Journal of Nuclear Medicine
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• v.28 no.2
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• pp.200-205
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• 1994

그레이브스 갑상선기능항진증은 자가면역질환의 하나로 방사성 옥소가 간편하고 경제적이며 효과적인 치료법임이 알려져 있는데 방사성 옥소 투여 후 갑상선 조직의 자극 및 파괴에 따라 각종 항원의 노출의 증가와 이에 대한 자가항체의 변동이 예상된다. 저자들은 추정 갑상선 무게를 고려한 6-10 mCi의 방사성 옥소를 투여 받은 그레이브스 갑상선기능항진증 환자 90명을 2년간 추적하여 치료 전 후의 혈청 갑상선자극 면역글로불린(TBIIl)활성도와 thyroglobulin 및 antithyroglobulin antibody의 변화를 관찰하였다. 1) 대상환자 90명의 연령분포는 14-58세(중앙치 30)였으며 여자가 72명(80%)이었다. 2) 평가대상 환자 중 치료 전 TBIIl 활성도가 정상범위였던 경우는 15명(30%)이었고 증가된 경우는 35명(70%)이었다. 치료 전보다 치료 3개월 후에 TBII 활성도가 더 증가된 경우는 31명(62% )이었다. 3) TBII 활성도가 치료 전에 증가하였거나, 치료 전에 정상범위였다가 치료 3개월 후에 증가한 환자의 TBII 활성도의 동태는 치료 3개월 후에 가장 높았고 그 후 점차 감소하였다. 이들의 TBIIl 활성도가 15%이내로 정상화된 정도는 치료 후 6개월에 40%, 12개월에 82%였다. 4) 치료 전 antithyroglobulin antibody가 양성인 경우 80%에서 3개월 후에도 혈청 thyroglobulin의 동태는 치료 3개월 후에 높았다가 증가가 없었으며 치료 전 antithyroglobulin antibody가 음성인 경우 60%에서 치료 3개월 후에 혈청 thyroglobulin의 증가가 있었다. 5) antithyroglobulin antibody가 음성인 경우의 혈청 thyroglobulin의 동태는 치료 3개월 후에 높았다가 점차 감소하는 경향을 보였으며 antithyroglobulin antibody가 양성인 경우의 혈청 thyroglobulin의 동태는 치료 후 시간이 지남에 따라 점차 감소하였다. 6) 치료 전 antithyroglobulin antibody가 음성인 경우 치료 후 시간 경과에 따라 동시에 측정한 혈청 TBII 활성도와 thyroglobulin 사이에는 통계적으로 유의한 상관관계가 있었다(p<0.01). 한편 치료 전 antithyroglobulin antibody가 양성인 경우 치료 후 시간 경과에 따라 동시에 측정한 혈청 TBII 활성도와 thyroglobulin 사이에는 통계적으로 유의한 상관관계가 없었다(p= 0.16). 이상의 결과로 방사성 옥소를 투여 받은 그레이브스 갑상선기능항진증 환자에서 혈청 TBII 활성도는 항갑상선제를 투여 받은 경우와는 달리 초기에 증가하였다가 시간이 지남에 따라 점차 감소함을 알 수 있었으며 그 감소 정도는 항갑상선제만을 쓴 경우보다 더 빠를 것으로 생각된다. 따라서 혈청 TBII 활성도와 thyroglobulin은 방사성 옥소 치료효과의 관찰에 중요한 역할을 할 것으로 생각되며 특히 antithyroglobulin antibody가 음성인 경우 혈청 thyroglobulin은 혈청 TBII 활성도를 반영할 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• v.52 no.9
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• pp.1021-1028
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• 2009

Purpose:Medical therapy is the initial treatment for children with Graves disease to avoid complications of other treatments. However, optimal treatment for childhood Graves disease is controversial because most patients require relatively long periods of medical therapy and relapse is common after medication discontinuation. Therefore, this study aimed to search clinical or biochemical characteristics that could be used as remission predictors in Graves disease. Methods:We retrospectively studied children diagnosed with Graves disease, treated with anti-thyroid agents, and observed for at least 3 years. Patients were categorized into remission and non-remission groups, and the groups were compared to determine the variables that were predictive of achieving remission. Results:Sixty-four patients were enrolled, of which 37 (57.8%) achieved remission and 27 (42.2%) could not achieve remission until the last visit. Normalization of thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII) after treatment was faster in the remission group than in the non-remission group (remission group, $15.5{\pm}12.07$ vs. non-remission group, $41.69{\pm}35.70$ months). Thyrotropin-releasing hormone (TRH) stimulation tests were performed in 28 patients. Only 2 (8.3%) of 26 patients who showed normal or hyper-response in TRH stimulation test relapsed. Binary logistic regression analysis identified rapid achievement of TBII normalization after treatment as a significant predictor of remission. Six percent of patients achieved remission within 3 years and 55.8% achieved it within 6 years. Conclusion:Rapid achievement of TBII normalization can be a predictor of remission in childhood Graves disease. The TRH stimulation test can be a predictor of maintenance of remission.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.175-180
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• 2009

Purpose: Detection of TSH-binding inhibitor immunoglobulin (TBII) in patients with hyperthyroidism is an important result of Graves' disease (GD) and hyperthyroidism treatment. This has been made out an inspection by commercial radio-receptor assays. To increase the sensitivity and the specificity of the assay, many results of the assay were reported. In this study we evaluated the clinical usetulness of TBII assays by the Comparative method. Material and Methods: We were measured by using healthy control group (n=30, male=20, female=10) of Seoul National University Hospital Healthcare System Gangnam Center from January to March in 2009. Similarly, We were measured by using hyperthyroid (TSH<$0.05\;{\mu}IU/mL$, FT4>1.80 ng/dL) experimental group (n=58, male=14, female=44) of division of endocrinology and metabolism department of internal medicine Seoul National University Hospital from January to March in 2009. We made a comparative study of each two assays from the first generation to the third generation. We were used of TSAb assay as a measurement of GD diagnostic technique. Results: The specificity of healthy control group was 100% according to the generation. (Specificity=100%, n=30) The sensitivity of hyperthyroid experimental group were the first generation RSR<%> (79.3%, n=58), RSR (51.7%, n=58), the second generation RSR-CT (93.1%, n=58), BRAHMSCT (98.3%, n=58), the third generation ELISA (94.6%, n=56), ECLIA (97.7%, n=58) and TS-Ab<%> (93.5%, n=46). Conclusion: We were used of TSAb assay as a measurement of GD diagnostic technique, The result of data showed a high correlation between the third generation TBII assay and the second generation TBII assay ($R^2$=0.923). Instead of the first generation assay, the second generation assay can be more useful in clincal diagnosis.

• The Korean Journal of Nuclear Medicine
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• v.22 no.2
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• pp.171-174
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• 1988

Thyrotropin binding inhibitory immunoglobulin (TBII) and thyroid stimulating antibody (TSAb) activities were measured in the thyroidal and peripheral venous blood samples at the time of subtotal thyroidectomy from twenty one patients with Graves' disease prepared for surgery with antithyroid drugs. There was no difference in TBII and TSAb activities between thyroidal and peripheral blood samples. These findings were regarded that while intrathyroidal lymphocytes are major site of thyrotropin receptor antibody (TRAb) production, similar levels are found in thyroidal and peripheral veins and that this in vivo study cannot exactly ascertain the TRAb producing site.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.76-82
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• 2003

Purpose : The aim of this study was to determine whether differences exist in the presentation, clinical course, and outcome of Graves' disease between prepubertal children and adolescents. Methods : A retrospective chart review of 14 prepubertal(PREPUB, $7.2{\pm}0.9yr) and 38 pubertal (PUB, $12.4{\pm}1.5yr$) children with Graves' disease between January 1989 and November 1995 at St. Mary's Hospital and Kangnam St. Mary's Hospital was undertaken. Results : There were no significant differences in $T_3$, $T_4$, TSH between two the groups at diagnosis. The PUB group had significantly higher titers of antimicrosomal antibody(positive dilution factor $11,727.3{\pm}22,888.4$) than did the PREPUB group($2,111.5{\pm}2,285.0$, P<0.001). The PREPUB group had significantly higher titers of TSH-binding inhibitory immunoglobulin(TBII, $62.5{\pm}39.6$) than did the PUB group($44.9{\pm}10.4$, P<0.05) before treatment started. The duration(months) of medical therapy before thyroid function tests were normalized was longer in the PREPUB group than in the PUB group($T_3:6.8{\pm}5.0$ vs. $5.4{\pm}13.2$, $T_4:2.3{\pm}1.9$ vs. $2.1{\pm}2.2$, $TBII:26.7{\pm}24.0$ vs. $20.8{\pm}12.1$), especially that of TSH was significantly longer in the PREPUB group($14.6{\pm}11.0$ vs. $6.8{\pm}7.8$, P< 0.05). Total length of medical therapy was significantly longer in the PREPUB group than the PUB group($52.3{\pm}19.3$ vs. $37.9{\pm}16.3months$, P<0.01). During three years of antithyroid drug therapy, in the PREPUB group, the remission rate was lower and the relapse rate was higher than in the PUB group. Total length of treatment correlated negatively with chronological age(P=0.03). Conclusion : Prepubertal children require longer medical therapy to achieve a remission than do pubertal children. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.

• Korean Journal of Head & Neck Oncology
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• v.11 no.2
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• pp.185-190
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• 1995

Transient and permanent hypocalcemia after various types of thyroidectomy are well-known complications, and are more common after bilateral subtotal thyroidectomy for Graves' disease. However, their causative mechanisms are not well explained. Four hundred thirty patients with Graves' disease who underwent bilateral subtotal thyroidectomy from January 1983 through December 1992 were analyzed to determine the incidence and risk factors for the development of postthyroidectomy hypocalcemia. Of the 430 patients underwent bilateral subtotal thyroidectomy, symptomatic transient and permanent hypocalcemia developed in 24.2 % (104/430) and 0.5 % (2/430), respectively. With analysis of potential risk factors, the increase in incidence of the postthyroidectomy hypocalcemia was found to be statistically related to the larger thyroid gland, the larger amount of blood loss during thyroidectomy, the smaller remnant thyroid tissue, the higher levels of serum alkaline phosphatase and TBII titers. Our data suggest that impairment of parathyroid gland blood supply, degree of thyrotoxic osteodystrophy and autoimmune process of each patient are regarded as main mechanisms of postthyroidectomy hypocalcemia in patients with Graves' disease.

• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.27-31
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• 1988

In Graves' disease, changes in orbital tissue and structure are casued by inflammatory infiltation, which induces increase of capillary permeability and breakdown of blood-tissue barriers. Using the uptake of $^{99m}Tc-DTPA$ in inflammatory lesion, Eye/Brain radioactivity ratios in brain scintigraphy were evaluated in 15 normal controls and 40 Graves' patients. The results were as follows; 1) Eye/Brain radioactivity ratio was significantly higher in Graves' ophthalmopthy group than in control group (p < 0.005). 2) In Graves' ophthalmopathy, Eye/Brain radioactivity ratio was significantly higher in active (progressive) group than in inactive (non-progressive) group (p < 0.05). 3) There was no correlation between class of ATA classification of Graves' ophthalmopathy and Eye/Brain radioactivity ratio. 4) There was no correlation between Eye/Brain radioactivity ratio and serum activity of TBII. In conclusion, Eye/Brain radioactivity ratio using $^{99m}Tc-DTPA$ brain scintigraphy may be useful to determine the activity of Graves' ophthalmopathy and whether treatment of Graves' ophthalmopathy is necessary or not.