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BACKGROUND: Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, IL-1 and TNF-a promote bone resorption by stimulating the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of these cytokines are mediated by estrogen. We performed this study to evaluate the effect of ovariectomy on bone mineral density and levels of cytokines in the culture media of bone marrow monocytes. METHODS: The experimental animals were 23 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 176.8 gm at the beginning of the study. Bilateral ovariectomy (n=13) and sham-operation (n=10) were performed in all rats from a ventral approach. Bone mineral density (BMD) of the total body and levels of IL-1 and TNF-a of culture media of bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH, FSH, E2 were measured by RIA assay. RESULTS: BMD of total body was lower after ovriectomy (0.24+-0.04g/cm) than before ovariectomy (0.27+-0.03g/cm), but there was no statistically significant difference in sham-operation group. Serum levels of LH, FSH were higher after ovariectorny (0.87+-0.36 mIU/mL, 9.47+-1.26 mIU/mL) than before ovariectomy (0.10+-0.06mIU/mL, 2.09+-0.41mIU/mL) (p<0.01) and serum level of E was lower after ovariectomy (10.98+-8.71pg/mL) than before ovariectomy (7350.77+-417.29 pg/mL) (p<0.01), respectively. Levels of IL-1 and TNF-a in culture media of bone marrow monocytes were higher after ovariectomy (23.48+-3.98pg/mL, 52.64+-5.31 pg/mL) than before ovariectomy (9.72+0.94pg/mL, 24.37+-3.39pg/mL) (p<0.01), but there were no statistically significant differences in the sharn-operation group. CONCLUSION: It is possible that increased production of IL-1 and TNF-a in estrogen deficiency induced by ovariectomy occures in the bone microenvironment and these cytokines may play a critical causal role in inducing bone loss.
Animals ; Bone Density* ; Bone Marrow* ; Bone Remodeling ; Bone Resorption ; Culture Media* ; Cytokines* ; Enzyme-Linked Immunosorbent Assay ; Estrogens ; Female ; Humans ; Interleukin-1 ; Monocytes* ; Osteoclasts ; Ovariectomy* ; Rats* ; Rats, Sprague-Dawley

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Non-association of Pvull and Xval Estrogen receptor Genotypes with Bone Mineral Density and Bone Markers in Korean Premenopausal Women.

Hyun Koo YOON ; Ho Yeon CHUNG ; In Gul MOON ; Chang Hoon YIM ; Sang Woo KIM ; Ki Ok HAN ; In Kwon HAN ; Hun Ki MIN ; Dong Won SUH ; Dong Hee CHO ; Bo Kyung PARK ; Jong Tae CHOI

Journal of Korean Society of Endocrinology.1997;12(2):207-214.

BACKGROUND: Bone mineral density (BMD) is under strong genetic control. A recently reported case of severe estrogen resistance caused by a germ-line mutation at the estrogen receptor gene locus suggests the possibility that other variants of the estrogen receptor (ER) gene could be responsible for the heritable components of bone density. METHODS: Two restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as PvuII and XbaI, and their relationship to bone mineral density (BMD) and bone turnover markers were examined in 95 healthy premenopausal women. Their mean age was 29 +-6.9 years (mean+-SD). RESULTS: The distribution of the PvuII and XbaI RFLPs was as follows: PP 20 (21.1%), Pp 40 (42.1%), pp 35 (36.8%), and XX 5 (5.3%), Xx 33 (34.7%), xx 57 (60.0%) (capital letters signify the absence of, and lower case letters signify the presence of the restriction site of each RFLP). There was no significant relation between ER genotypes and BMD measured at several sites such as lumbar spine (L2-4), distal forearm, and femoral neck. Also no significant genotypic differences were found in the several biochemical markers and sex hormone status. CONCLUSION: These data indicate that these polymorphisms are not predietive of bone turnover nor BMD in a sample of healthy Korean premenopausal women.
Biomarkers ; Bone Density* ; Estrogens* ; Female ; Femur Neck ; Forearm ; Genotype* ; Germ-Line Mutation ; Humans ; Osteoporosis ; Polymorphism, Restriction Fragment Length ; Spine

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Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease.

Won Bae KIM ; Hyun Kyung CHUNG ; Bo Youn CHO ; Hong Kyu LEE ; Chang Soon KOH ; Do Joon PARK ; Yeon Sahng OH

Journal of Korean Society of Endocrinology.1997;12(2):194-206.

BACKGROUND: It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.
Animals ; Antibodies* ; Clone Cells ; Cricetinae ; Cricetulus ; Female ; Graves Disease* ; Humans ; Hypothyroidism ; Ovary ; Rats ; Receptors, Thyrotropin* ; Thyroid Gland ; Thyrotropin*

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Heterogeneity of TSH Receptor Autoantibodies in Autoimmune Thyroid Disease.

Won Bae KIM ; Bo Youn CHO ; Kyoung Ah KIM ; Jae Hoon CHUNG ; Young Ki MIN ; Myung Shik LEE ; Moon Kyu LEE ; Kwang Won KIM

Journal of Korean Society of Endocrinology.1997;12(2):176-193.

BACKGROUND: It has been known that most of thyroid stimulating antibodies (TSAbs) may interact with epitopes near N-terminal, and thyroid stimulation blocking antibodies (TSBAbs) near C-terminal on the extracellular domain of TSH receptor. However, many authors have reported different results about epitopes reacting with TSH receptor autoantibody (TRAb). TSBAbs inhibit thyroid stimulation of TSH and TSAbs at the receptor level. However, it has been reported that there are some TSBAbs which bind to the other sites, not TSH receptor, or block post-reeeptor process. These findings raise the possibility that TRAbs may be heterogeneous according to the mechanism of action. In order to investigate the heterogeneity of TRAb, we undertook immuno-precipitation using synthetic peptides of TSH receptor and measured TRAb activities by FRTL-5 cells and chimeric CHO cells. METHODS: We studied 102 patients with autoimmune thyroid disease (Graves disease 32, Hashimotos thyroiditis 29, atrophic thyroiditis 41) and 35 healthy persons. Three synthetic peptide fragments of TSH receptor were used to perform immunoprecipitation with serum or IgG of patients and healthy persons, TSAb and TSBAb activities were measured by FRTL-5 cells and CHO cells transfected with wild-type and 2 mutant TSH receptor cDNA (Mc2, Mc1+2). Mc2 and Mcl+2 were rnade to substitute amino acid residues of 90-165, 8-165 of the TSH receptor with corresponding residues of LH/CG receptor, respectively. RESULTS: Two out of 10 IgGs extracted from Graves disease and 2 out of 9 IgGs from atrophic thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide I (amino acid residue 35-50). Four out of 18 IgGs from Graves disease, 9 out of 41 IgGs from atrophic thyroiditis, and 6 out of 14 IgGs from Hashimotos thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide II (amino acid residue 317-332). Only 2 out of 10 IgGs from Graves disease had specific bidings over 0.84% in immunoprecipitation with peptide III (amino acid residue 341-358). When 10 IgGs extracted from Graves disease were reacted with wild-type, Mc2, and Mcl+2 CHO cells, 7 IgGs in wild-type and 4 IgGs in Mc2 had positive for TSAb activities. In 10 IgGs from atrophic thyroiditis, 5 in wild-type, 5 in Mc2, and 3 in Mcl+2 CHO cells had positive for TSBAb activities. In Hashimoto's thyroiditis, only 1 with hyperthyroidism had positive for TSAb activity in wild-type and 1 with hypothyroidism had positive for TSBAb activities in both of wild-type and Mc2 CHO cells. Therefore, patients with Graves disease were divided into at least 3 groups according to the TSAb activities measured by wild-type, Mc2, Mcl+ 2 CHO cells and TBII activities. And patients with atrophic thyroiditis were divided into at least 4 groups according to the TBII activities, TSBAb activities by wild-type, Mc2, Mcl+2 CHO cells and FRTL-5 cells. CONCLUSION: From these results, epitopes of TSH receptor reacting with TSAb or TSBAb in autoimmune thyroid disease may be scattered in the TSH receptor, although epitopes of TSAb tend to be near N-terminal and those of TSBAb near C-terminal. Graves disease or atrophic thyroiditis were divided into 3 or 4 groups according to the TBII and TRAb activities. Therefore, TRAb detected in autoimmune thyroid disease may be heterogenous.
Animals ; Antibodies, Blocking ; Autoantibodies* ; CHO Cells ; Cricetinae ; DNA, Complementary ; Epitopes ; Graves Disease ; Humans ; Hyperthyroidism ; Hypothyroidism ; Immunoglobulin G ; Immunoglobulins, Thyroid-Stimulating ; Immunoprecipitation ; Peptide Fragments ; Peptides ; Population Characteristics* ; Receptors, Thyrotropin* ; Thyroid Diseases* ; Thyroid Gland* ; Thyroiditis

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Piruitray Thyrotropin-Secreting Tumors in Korean.

Chul Hee KIM ; Ghi Su KIM ; Hong Kyu KIM ; Joong Yeol PARK ; Young Kee SHONG ; Sang Bum HONG ; Jung Min KO ; Chang Jin KIM

Journal of Korean Society of Endocrinology.1997;12(2):165-175.

BACKGROUND: Thyrotropin-secreting pituitary adenoma is an uncommon disease and about 150 cases has been reported in the world literature. In Korea, only seven cases were reported as yet. The authors recently experienced four cases of TSH secreting pituitary tumor and analyzed the clinical characteristics and treatment outcomes of TSH-secreting tumors in Korean. METHODS: We analyzed clinical records of the four cases who had been recently treated at Asan Medical Center and the Korean literature which deals with the previously reported seven cases of TSH-secreting pituitary tumor. RESULTS: The average age at diagnosis was 37 years (ranging from 11 to 55 years). Four were men and seven were women. After the detection of hyperthyroidism, TSH-secreting pituitary adenoma was diagnosed 3.6 years later on the average. Ten patients presented with hyperthyroidism, but one had primary hypothyroidism. Typical features of acromegaly were observed in two patients. Visual disturbance was present in three cases, and galactorrhea was present in one case. Serum TSH concentrations ranged from 1.5 to 42.5uIU/mL showing mildly elevated or unsup-pressed TSH levels despite of elevated serum thyroid hormone concentrations. Among six cases in whom a-subunit level was measured, five showed elevated a-subunit level and a-subunit/TSH molar ratio. Two of 11 cases had microadenoma and the remainder had macroadeno#ma. Immunohisto-cheical studies were done in eight cases and revealed that three were positive for TSH only and five patients were positive for multiple hormones. Eight patients underwent transsphenoidal pituitary surgery and seven (88%) of them were cured. External irradiation or octreotide was used as adjunctive treatment in three cases. After treatment, TSH levels decreased in all six patients studied, hyperthyroidism was eliminated in all eight patients studied and visual disturbance was improved in two patients. CONCLUSION: Clinical characteristics of TSH-secreting pituitary adenoma in Koreans were similar with world literature, but were more common in women, had less visual disturbance and better surgical results. Diagnosis was commonly delayed for several years. TSH-secreting pituitary adenoma may be diagnosed more frequently and earlier with widespread use of sensitive TSH assay and early and proper diagnosis would lead proper treatments with improved outcome.
Acromegaly ; Asian Continental Ancestry Group ; Chungcheongnam-do ; Diagnosis ; Female ; Galactorrhea ; Humans ; Hyperthyroidism ; Hypothyroidism ; Korea ; Male ; Molar ; Octreotide ; Pituitary Neoplasms ; Pregnancy ; Thyroid Gland

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Clinical Features of Pityitary Hyperplasia.

Kyoung Rae KIM ; Sung Kil LIM ; Young Jun WON ; Seok Ho KWON ; Bong Soo CHA ; Young Duk SONG ; Hyun Chul LEE ; Kap Bum HUH ; Bo Young CHOUNG ; Su Yeun NAM ; Sun Ho KIM ; Tse Sung KIM ; Jae Hwa UM

Journal of Korean Society of Endocrinology.1997;12(2):155-164.

BACKGROUNDS: Pituitary hyperplasia can mimic pituitary adenoma. In MRI, enlarged pituitary gland is enhanced homogenously with upward convexity of the superior margin of the gland .The best definition of hyperplasia in the pituitary hyperplasia seems to be a multiplication of one or more cell types. But definition, etiology and clinical courses of this disease are not clear, METHOD: We reviewed clinical symptoms, MRI, and pathologic findindings in 6 patients with pituitary hyperplasia. RESULT: 1. Major clinical symptoms were headache (100%), visual field defect (84%), polyuria/polydipsia (64%), and irregular mensturation (32%). Other symptoms were amenorrhea (16%) and galactorrhea (16%). 2. Three of five cases showed abnormal responses to combined pituitary function test, 3. MRI findings were pituitary hyperplasia (4), macroadenoma (l), and microadenoma (1). 4. In two operated cases, there was no adenoma. One case showed hyperplasia of lactotroph cells, the other was hyperplasia of gonadotroph cells confirmed by the examination of immunocytochemistry. CONCLUSION: Pituitary hyperplasia should be considered in patients with enlarged pituitary gland without focal mass lesion.
Adenoma ; Amenorrhea ; Female ; Galactorrhea ; Gonadotrophs ; Headache ; Humans ; Hyperplasia* ; Immunohistochemistry ; Lactotrophs ; Magnetic Resonance Imaging ; Pituitary Function Tests ; Pituitary Gland ; Pituitary Neoplasms ; Pregnancy ; Visual Fields

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