Graves 병에서 배양된 백서 갑상선 세포 ( FRTL - 5 ) 를 이용한 갑상선 자극항체의 측정 - 기본적 검토 및 임상적 의의 -

조보연(Bo Youn Cho),송영기(Young Kee Shong),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min),이문호(Mun Ho Lee) 대한내과학회 1988 대한내과학회지 Vol.34 No.2

N/A We tried to assess the best conditions to measure thyroid stimulating antibodies (TSAb) using cultured rat thyroid cell ling (FRTL-5), And also to evaluate the frequencies of TSAb in Graves' disease, changes of TSAb activities during antithyroid drug treatment, and whether the presence of TSAb at the end of treatment can predict the relapse, we measured TSAb using FRTL-5 cells in 40 normal controls and 179 patients with autoimmune thyroid diseases. The results are as following; 1) The cAMP responses of FRTL-5 cells to TSH and TSAb began to increase from 3 days after TSH withrawal from culture media and reached peak response at the 7th day, and thereafter decreased. 2) The cAMP responses of FRTL-5 cells to TSH and TSAb increased in relation to incubation times. 3) The dose-response curves of TSH and TSAb, stimulating cAMP production in FRTL-5 cells, showed similary sigmoid curves. The minimum levels of TSH and TSAb which showed significant increase of cAMP were 2-5 μU/ml and 0.15-0.3mg/well, respectively. 4) Intracelluar cAMP levels were correlated closely with extracelluar cAMP levels. About 75-80% of total cAMP levels was released into culture supernatant. 5) The frequencies of detectable TSAb in 57 patients with untreated Graves' disease, in 55 patients with euthyroidism under treatment and in 18 patients with remission were 93%, 56.4% and 11.1%, respectively. However, only 2 out of 21 patients with Hashimoto's thyroditis had low titers of TSAb in their sera. TSAb were not present in sera of all 28 patients with primary nongoitrous myxedema. 6) TSAb activites were singnificantly correlated with TBII activities (r=0.635, p<0.001). 7) In remission group, TSAb activities decresed significantly from 3 months after treatment, and disappeared in alomost all cases within 12 months. However, those activities were not changed significantly untill the end of treatment in relapse group. 8) The positive rate of TSAb in 27 patients who were in remission after treatment was 38.7%, however, that in 28 patients who relapse within 12 months aftr discontinuation of drugs was 77.8%. The predicitve value of TSAb for relapse was 67.7%, which was similar with that of TBII (71.4%). These findings suggest that determination of TSAb using FRTL-5 cells is very sensitive and specific method and that TSAb is one of major cause of hyperthyroidism in Graves disease, and its determination can be useful for the evaluation of clinical course and prognosis in patients with Graves disease.

갑상선 세포의 성장에 대한 TSH 및 IGF - I 의 신호전달 과정에서 백일해 독소 예민성 G - 단백의 역할

조보연(Bo Youn Cho),이동수(Dong Soo Lee),이가희(Ka Hee Yi),송민호(Min Ho Shong),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min) 대한내과학회 1991 대한내과학회지 Vol.41 No.1

N/A To evaluate the effect of pertussis toxin sensitive G-proteins on the growth of thyrocytes by TSH and IGF-I, we measured 3H-thymidine incorporation into FRTL-5 cells stimulated by TSH and/or IGF-I. Thymidine incorporation into FRTL-5 cells by TSH(1 mU/ml) or IGF-I (10 ng/ml) was significantly inhibited by the pretreatment of pertussis toxin (25 ug/ml). Adenosine (1mM) inhibited both TSH-and IGF-I- stimulated thymidine incorporation into FRTL-5 cells and the synergistic effect of TSH and IGF-I. This inhibitory effect of adenosine on TSH-or 1GF-I-stimulated thymidine incorporation was blocked partially by the pretreatment of pertussis toxin. However, the inhibition of the synergism of TSH and IGF-I by adenosine was not altered by the pretreatment of pertussis toxin. Indomethacin (100 uM) inhibited TSH effects by 60% and inhibieed IGF-1 effects by 5096 at 24 hours of incubation and then enhanced IGF-I effects in the prolonged incubation. Indomethacin blunted the synergism of TSH and IGF-I. These inhibitory effects of indomethacin were altered by the pretreatment of pertussis toxin. The pretreatment of pertussis toxin did not affect the inhibitory effect of indomethacin on the synergism of TSH and IGF-I at 24 hours of incubation. However, in the prolonged incubation (72 hours) the pretreatment of pertussis toxin significantly blocked the indomethacin effect. These findings suggest that pertussis toxin-sensitive G-proteins are involved in the signal transduction of TSH and/or IGF-1-stimulated growth of FRTL-5 cells and arachidonate metabolites should be involved in the mediation of synergism of growth stimulation induced by TSH and IGF-l in FRTL-5 cells.

한국 갑상선학의 역사

조보연 ( Bo Youn Cho ) 대한갑상선학회 2008 International Journal of Thyroidology Vol.1 No.1

배양된 쥐 갑상선세포 성장에 미치는 각종 성장인자들과 TSH 수용체항체간의 상호작용 및 그 기전에 관한 연구

조보연(Bo Youn Cho),송영기(Young Kee Shong),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min) 대한내과학회 1989 대한내과학회지 Vol.37 No.3

N/A To evaluate the interaction of various growth factors and TSH receptor antibodies (TRAb) on the growth of cultured rat thyroid cells, FRTL-5 cells, and to verify their mechanisms of action, we measured 3H-thymidine incorporation into FRTL-5 cells with various combinations of TSH, Graves' IgG and other growth stimulators (insulin, IGF-I, multiplication stimulation activity, forskolin, dBcAMP and phorbol ester). We evaluated the effects of blocking TRAb and adenosine on the growth factor-stimulated growth of FRTL-5 cells. Insulin, IGF-I and MSA increased 3H-thymidine incorporation into FRTL-5 cells and showed a synergistic effect when incubated simultaneously with TSH or Graves IgG. Forskolin, PGE2, and dBcAMP also increased 3H-thymidine incorporation by themselves and their effects were synergistically potentiated by insulin and IGF-I. Adenosine inhibited both TSH and Graves' IgG induced 3H-thymidine incorporation into FRTL-5 cells. Blocking TRAb inhibited both TSH and Graves' IgG induced 3H-thymidine incorporation, but did not inhibit the effects of insulin, IGF-I, forskolin and dBcAMP on the growth of FRTL-5 cells. Phorbol ester (TPA) did stimulate the growth of FRTL-5 cells by itself and inhibited both TSH and Graves IgG induced 3H-thymidine incorporation into FRTL-5 cells. These results suggest that 1) there might be two or more signal transduction systems for the growth of thyroid cells; TSH and Graves IgG stimulate the growth of thyroid cells through the adenylate cyclase-cAMP system, and IGF-I and other growth facors act through another system, and 2) blocking TRAb may inhibit the growth of thyroid cells by inhibiting TSH-stimulated cAMP generation.

갑상선 호르몬의 외부정도 관리 분석 - 1989년 9월부터 1990년 8월까지 첫해 시행 결과 -

이동수,조보연,곽철은,서일택,정준기,이명철,고창순 ( Dong Soo Lee,Bo Youn Cho,Cheol Eun Kwark,Il Taek Seo,June Key Chung,Myung Chul Lee,Chang Soon Koh ) 대한핵의학회 1991 핵의학 분자영상 Vol.25 No.2

장기간의 갑상선 호르몬 치료가 골밀도에 미치는 영향

이가희(Ka Hee Yi),조보연(Bo Youn Cho),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min) 대한내과학회 1991 대한내과학회지 Vol.40 No.3

N/A Both spontaneous and exogenous hyperthyroidism result in osteoporosis by increased bone-remodeling. We studied the effect of long-term suppressive thyroxine therapy on axial bone density in 59 female patients (28 premenopausal, 31 postmenopausal). Bone densities of the lumber spine, femoral neck, femoral trochanter and Wards triangle were measured by dual photon absoptiometry and compared with those of age, sex, menopause-matched normal controls. The levels of serum osteocalcin, alkaline phosphatase, calcium, phosphorus were measured in patients and their correlations with bone densities were analyzed. The degree of change in bone density was quantified with Z transformation. Bone densities of lumbar spine and femur were decreased significantly in postmenoausal patients when compared with controls (lumbar spine: 0.8696±0.116 vs. 0.9264±0.043(g/cm²), femoral neck: 0.7246±0.096vs. 0.8020±0.037(g/cm²), femoral trochanter: 0.6021±0.088 vs 0.6489±0.032(g/cm²), Ward's triangle: 0.6216±0.128 vs. 0.6900±0.048(g/cm²), p<0.05) but in premenopausal women, there were no differences in bone densities between patients and controls. Bone densities were negatively correlated with serum ostocalcin (lumbar spine r=-0.572, femoral neck r=-0.561, femoral trochanter r=0.646, Ward's triangle r =-0.581, p<0.001), and alkaline phosphatase (lumbar spine r= -0.615, femoral neck r =-0.610 femoral trochanter r=-0.452, Ward's triangle r=-0.573, p<0.01) and Z value were negatively correlated with osteocalcin (lumber spine r=-0.427 femoral neck r=-0.473 femoral trochanter r=-0,567 Ward's triangle r=-0.464, p<0.01), and patients age (lumbar spine r=-0.464 femeral neck r=-0. 350, femoral trochanter r=-0.425, Ward. triangle r=-0.310, p<0.05). These results suggest that sucblinical hyperthyroidism induced by suppressive thyroxine therapy can cause osteoporosis by high bone turnover which is severer in older postmenoausal women. Therefore regular evaluation of bone mineral density and warning for osteoporosis will be necessary.

Graves 병에서 항갑상선제 장기치료후 예후인자로서의 TSH 수용체 항체와 TRH 자극시험

임성희(Sung Hee Ihm),조보연(Bo Youn Cho),이홍규(Hong Kue Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min),이문호(Mun Ho Lee) 대한내과학회 1987 대한내과학회지 Vol.33 No.1

N/A To evaluate the prognostic value of TRH receptor antibodies in Graves' disease and to compare it with TRH stimulation test, TBII activities were measured by radioreceptor assay in 59 patients with Graves' disease during and after 13 months of antithyroid drug therapy and TRH stimulation test was performed in 37 patients in 3 months after drug withdrawal. Within 12 months after the discontinuation of the drugs, 33 patients out of 59 patients (56%) relapsed. Out of 27 patients whose TBII were postive at the time of drug withdrawal 22 patients (8l.5%) relapsed. However in 32 patients whose TBII returned to normal range at the time of durg withdrawal, 21 patients (65.6%) remained in remission for 12 months and 11 patients (34.4%) relapsed. In 14 patients who showed no response to TRH stimulation, 11 patients (78.6%) relapsed. However in 23 patients who showed normal response to TRH stimulation, 19 patients (82.6%) remained in remission and only 4 patients (17.4%) relapsed. In patients who had positive TBII at the time of drug withdrawal and showed no respons to TRH stimulation, 5 patients (83.3%) relapsed, In contrast, 19 patients who had negative TBII at the time of drug withdrawal and normal response to TRH stimulation, 16 patients (84,2%) remained in remission for 12 months. There were no significant differences in predictive values for relapse among TBII positive group, TRH non-responsive group and both abnormal group. These results suggest that 1) positive TBII activities at the end of longterm antithyroid drug treatment is a useful indicator predicting subsequent relapse, and 2) prognostic value of the TBII activities seems to be of the same order as the TRH stimulation test in predicting relapse.

뇌하수체 - 갑상선 축의 평가에 있어 면역방사계수측정법에 의한 혈청 TSH 의 기저치 측정의 의의

서교일(Kyo Il Suh),조보연(Bo Youn Cho),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min),이문호(Mun Ho Lee) 대한내과학회 1988 대한내과학회지 Vol.34 No.6

N/A To evaluate whether thyrotropin(TSH) values measured by sensitive immunoradiometric assay(IRMA) can be used as an indicator of pituitary-thyroid status, serum triiodothyronine(T3) and thyroxine(T4) as well as TSH were measured before and after thyrotropinreleasing hormone(TRH) stimulation in 30 normal subjects, 17 patients with hyperthyroidism and 67 patients receiving chronic oral T, therapy for thyroid cancer. IRMA of TSH involves use of two monoclonal antibodies. The detection limit of the assay was 0.04 mU/L and intrassay and interassay variation was less than 5% in TSH concentration of 2.4 and 31.6 mU/L, Over the undetectable to nomal TSH range, an excellent correlation was observed between basal TSH levels and TRH stimulated TSH increment was observed between basal TSH levels and TRH stimulated TSH increment (r=0.94). When the subjects were grouped by their resting free T. index (FT,I), the curve was found to be steeper in high FT4I group (FT4I>9.4) than normal FT4I group (FT4I<9.4) (y=0.82+113x vs y=0.78+1.28x). In 67 patients with thyroid cancer on suppression therapy, 43 had both undetectable basal TSH levels and no TSH response to TRH stimulation while 7 patients had undetectable basal TSH levels but preserved TSH response to TR~H. Measurable TSH response to TRH were found in all patients with detectable basal TSH. Therefore, when basal TSH value of 0.04mU/L was used as a criterion, sensitivity and specificity for prediciting pituitary suppression were 84% and 100% respectively while those were 78% and 72% in case FT4I of 12 was used as a criterion. These findings suggest that the TSH values measured by sensitive IRMA represents status of pitutitarythyroid axis and can be used as a sensitive indicator of pituitary suppression.

정상인 및 갑상선질환 환자에서 Thyroxine 투여에 따른 TSH 분비능 억제에 관한 연구

고창순 ( Chang Soon Koh ),조보연 ( Bo Youn Cho ),문대혁 ( Dae Hyuk Moon ),이동수 ( Dong Soo Lee ),김상은 ( Sang Eun Kim ),송영기 ( Young Ki Song ) 대한내과학회 1985 대한내과학회지 Vol.29 No.2

갑상선질환 및 비갑상선질환에서 TSH 측정의 진단적 의의

이가희(Ka Hee Yi),조보연(Bo Youn Cho),이홍규(Hong Kyu Lee),고창순(Chang Soon Koh),민헌기(Hun Ki Min) 대한내과학회 1991 대한내과학회지 Vol.40 No.3

N/A The diagnostic value of basal serum TSH measured by ultrasensitive IRMA was evaluated. For hyperthyroidism, we measured serum TSH by IRMA in 499 patients with thyroid diseases and analysed the causes of undetectable TSH levels in 821 serum samples referred for thyroid function test during one month (May, 1988). For euthyroid sick syndrome in nonthyroidal ill- nesses, we measured serum TSH using IRMA in 411 patients hospitalized due to nonthyroida1 illnesses and in 105 randomly selected patients, T3, T3RU, T4, FT4I, FT4 and rT3 were also measured by RIA. The mean of serum TSH level in 178 normal controls was 1.39±0.76 μU/ml(log mean=1.18)and the 99% confidence range(mean±3SD) was 0.19~7.4 μU/ml. the serum TSH levels of 141 patients with Graves disease were below 0.19 μU/ml and those of 136 patients (96.4%) were undetectable. In patients with thyroid diseases other than Graves disease, the serum TSH levels were decreased below 0.19 uU/ml in 6. The diagnostic sensitivity of TSH by IRMA for hyperthyroidism was 100% (141/141), and specificity was 97.8%(271/277). 176 samples (21.4%) out of 821 sera referred for thyroid function test for one month showed undetectable TSH levels. The undetectable TSH lebels were caused by Graves' hyperthyroidism in 127(72%), Graves' disease under treatment (euthyroidism) in 38(22%), thyoxine treatment in 7(3.4%), subacute thyroiditis in 2(1%), and thyroid nodule in 2(1%). Among 411 patients hospitalized due to nonthyroidal illnesses (NTI), 16 patients (3.9%) showed undetectable or low (<0.19μU/ml) TSH levels and 4 patients (0.9%) showed raised (>7.4 μU/ml) TSH levels. 6(3%) of 20 patients with abnormal TSH levels had received steroid therapy which suppress TSH secretion and 1(5%) had received metoclopropamide which antagonize dopaminergic inhibition of TSH secretion. Only 13(3.2%) out of 411 patients showed abnormal TSH levels due to NTI. Results of thyroid function test in randomly selected 105 patients with NTI showed low total T3 levels in 79(75.2%), low total T4 in 31(29.5%), low FT4I in in 11(10.5%), raised FT4 in 17(16.2%), decreased FT4 in 5(4.8%), raised rT3 in 38(36.2%), decreased rT3 in 13(12.4%). In contrast, TSH levels were abnormal only in 6(5.7%), increased in 2(1.9%) and decreased in 4(3.8%) patients with NTI. Therefore basal seum TSH measured by IRMA can represent status of pituitary-thyroid axis both in patients with thyroid diseases, especially hyperthyroidism and nonthyroidal illnesses.