Endocrinology and Metabolism

Volume 14(2); June 1999

Original Articles

Relationship between the Expression of Growth Hormone-Releasing Hormone Receptor Gene and Endocrinologic Profiles in GH-Secreting Pituitary Adenomas.: Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Seung Joon Park, In Myoung Yang, Jung Taek Woo, Mi Sook Ryu, Chul Young Park, Sun Woo Kim; J Korean Endocr Soc. 1999;14(2):241-254. Published online January 1, 2001

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Growth hormone-releasing hormone (GHRH) plays a key role in the regulation of the proliferation and differentiation of somatomammotroph cells as well as secretion of GH. The actions of GHRH are mediated through the GHRH receptor (GHRH-R) that is a G protein coupled receptor with seven transmembrane domains. It has been demonstrated that alternative splicing occurs in the third cytoplasmic domain of rat and human GHRH-R mRNA, However, the clinical significance of the altemative splicing remains to be unsolved. To find an insight into the clinical significance, we investigate the correlation between the GHRH-R gene expression and a variety of clinical clinical and endocrinological findings in 11 acromegalic patients. METHODS: Eleven acromegalic patients (3 males and 8 females, mean age 43.5 years) were included in this study. Six endocrine tests were carried out to evaluate the GH seeretory function of tumors. Invasiveness of tumors were evaluated by preoperative MRI findings on the basis of Hardys classification. Sequence the gsp oncogene and estimate the GHRH-R gene expression by RT-PCR and in vitro transcription. RESULTS: Three different sized cDNA fragments, 250 bp, 700 bp and 810 bp, were found after RT-PCR. The amount of 250 bp fragment was higher than those of the other two fragments. The clinical findings (age, size, GH level, frequency of paradoxical response to TRH or GnRH, octreotide response, hypothalamic somatostatinergic activity) of the group with high expression of the 250 bp fragment did not significantly differ from those of the group with low expression. The GHRH-R gene expression of tumors with gsp oncogene did not significantly differ from that of tumors without gsp oncogene. CONCLUSION: These results suggest that the expression of GHRH-R gene may not be an important determinant for tumor growth, and the lower GH response to GHRH of tumors with gsp oncogene may not be attributed to the lower expression of GHRH-R gene. The expression of GHRH-R is likely to be regulated by a certain property of tumors for GH secretion and growth.

Effect of Isoproterenol on the Glucose-induced Hypothalamin Somatostatin Release.: Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, In Myoung Yang, Jung Taek Woo, Chul Young Park, Sun Woo Kim, Jung Hyun Ro, Sang Hwa Kim, Seung Joon Oh, Duk Yoon Kim; J Korean Endocr Soc. 1999;14(2):255-264. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Acute hypoglycemia stimulates somatostatin (SRIH) release from the hypothalamus, and which in turn suppress growth hormone (GH) secretion from the anterior pituitary gland. However, the exact mechanism of glucose increases the hypothalamic SRIH secretion is not well known. Beta-adrenergic pathway is known to stimulate the hypothalamus SRIH release. We, therefore, hypothesized that the glucose-induced SRIH release may be mediated by the stimulation of the central beta-adrenergic system, and investigated to determine whether a beta-adrermgic aganist, isoproterenol, contribute the suppressive effect of glucose on the GHRH-induced GH secretian. METHODS: Ten healthy young men, aged 23 to 26 years, were studied. Four endocrinological tests were carried out. (Test 1) GHRH (Bachem, CA, U.S.A.), 100pg bolus, was given intravenously at 0 minute. (Test 2) Glucose 100 gm dissolved in water, was given orally at -30 minute and GHRH was administered as Test 1. (Test 3) Isoproterenol (Isuprel, Sanofi Winthrop, USA), 0.012 mg/kg, wasinfused continuously between 0 minute and 120 minute, and GHRH was administered as Test 1. (Test 4) Isoproterenol, 0.012 mg kg was infused continuously between 0 minute and 120 minute, and glucose and GHRH were administered as Test 2. RESULTS: Oral glucose ingestion significantly suppressed the GHRH-induced GH secretion. The acute hyperglycemia significantly suppressed GHRH-induced GH secretion. The pretreatments with isoproterenol significantly suppressed the GHRH-induced GH levels. The pretreatment with glucose and isoproterenol suppressed the GHRH-induced GH levels more compared to those induced by glucose in Test 2. The GH levels in Test 4 did not significantly differ from those in Test 3. CONCLUSION: The results of this study suggests that the hypothalamic somatostatinergic activity induced by the oral glucose administeration is not mediated by the beta-adrenergic pathway in normal men. (J Kor Soc Endocrinool 14:255-264, 1999)

The Characterization of Glucocoritcoid Response Element(GRE) on the Promoter of Thyrotropin-Releasing Hormone(TRH) Gene.: Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, In Myoung Yang, Jung Taek Woo, Woon Won Chung; J Korean Endocr Soc. 1999;14(2):265-277. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We previously demonstrated that the promoter of rat TRH gene has GRE half site (TGTTCT) between -210 bp and -205 bp flanking with similar sequences of TPA response element (TRE), TAGTCA, at a distance of several base pairs from the GRE half site. It promps us to hypothesize that this composite GRE/TRE sequence can provide a site for interaction between glucocorticoid receptor (GR) and c-Jun. Thus, we investigated whether the composite sequence mediates transcriptional regulation induced by dexamethasone (DEX) and 12-O-tetradecanoyl phobol-13-acetate (TPA), and whether it binds GR and c-Jun. METHODS: A luciferase expressing plasmids that contain a part of rat TRH promoter including the composite sequence or their mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX increased the transcriptional activity of the plasmid containing the wild type GRE by 2.5 folds, and TPA increased the transcriptional activity by 4 folds. The simultaneous stimulation with DEX and TPA synergistically increased the transcriptional activity by 10 folds. Two mutants whose GRE half sits were altered showed no responses to DEX, and suppressed the TPA-induced or both agents-induced transcriptional activity by 50%. Two mutants whose TRE-like sites were altered suppressed the DEX-induced transcriptional activity by 20%, TPA-induced trarptional activity by 25%, and both agents-induced transcriptional activity by 50%. Gel retardation assay showed that the composite sequence fonned a complex with GR and its mutants bound to GR with remarkably less affinity. c-Jun also bound to the composite sequence to form two cornplexes with less affinity compared to the AP-1 consensus sequence. The mutants of the TRE-like sequence bound to c-Jun with a significantly lower affinity compared to that of the wild type. Simulateous binding of the composite sequence with GR and c-Jun did not form any larger complex. The complex of GR and the composite sequence was much smaller than that formed by c-Jun, suggesting that GR binds to the composite sequence as a monomer. CONCLUSION: These results suggest that the composite sequence of GRE half site and TRE-like site on the promoter of rat TRH gene provides binding sites for GR and c-Jun, which mediate the interaction between two signal transduction pathways. (J Kor Soc Endocrinol 14:265-277, 1999)

Analysis of Glucocorticoid Response Element and TPA Response Element of Rat Thyrotropin-Releasing Hormine Gene by Site-Directed Mutagenesis.: Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, In Myoung Yang, Jung Taek Woo, Woon Won Chung; J Korean Endocr Soc. 1999;14(2):278-292. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We previously demonstrated that a GRE/TRE composite sequence, which is located between 200 bp and 220 bp relative to the transcriptional start site of rat TRH gene, is responsible for the dexamethasone (DEX)- and TPA-induced transcriptional activation, and the transcriptional activation by DEX is mediated by interaction between glucocorticoid receptor (GR) and a TRE-binding transcriptional factor such as c-Jun. However, a non-specific binding with the transciption factors can not be excluded as the mutants used in the previous report could not inhibit the binding of GR and c-Jun completely, and it remains unclear which one of the two TRE-like sequences is critical for the interaction of the two transcription factors. METHODS: Luciferase expressing plasmids that contain a part of rat TRH promoter including the composite GRE sequence or its mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX or/and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX and TPA increased the transcriptional activity of the wild type composite sequence by 3 folds and 4 folds, respectively, and the combined stimulation increased the activity by 10 folds. The mutants of which all 6 nucleotides of the GRE half site were replaced and removed almost did not bind to GR and eould not enhance the transcriptional activity at all in response to DEX. The GRE-deleted mutant bound to c-Jun with a remarkably lower affinity and showed a lower response to TPA, whereas the GRE-replaced mutant bound to c-Jun with a similar affinity and showed a similar response to TPA compared to those of the wild type. In response to the combined simulation with DEX and TPA, the mutants showed 30-40% of the trancriptional activity of the wild type. Basal transcriptional activity of all the TRE mutants was significantly lower than that of the wild type. While they almost could not bind to c-Jun, their binding affinity to GR was comparable to that of the wild type. Whereas the DEX- and TPA-induced transcriptional activity of 5 TRE mutant was 10% and 15% of that of the wild type, it responded to those agents in a similar pattern as the wild type. The 3 TRE mutant and the mutant of both TRE sites did not respond to DEX and TPA. The GRE-deleted mutant hardly formed the DNA-protein complex as did the wild type, while the GRE -replaced mutant could form the complex in a less amount with nuclear extract of HeLa celL CONCLUSION: These results suggest that GRE/TRE composite sequence of rat TRH gene specifically binds to GR and c-Jun, providing a site for interaction between the two transcription factors, and that both TRE sites play an important role in basal transcription, and that the 3 TRE site is more critical in the interaction between GRE and TRE for DEX-induced transcriptional activation. (J Kor Endocrinol 14:278-292, 1999)

Serum Soloble Fas in Autoimmune Thyroid Disease.: Min Ho Song, Heung Kyu Ro, Hee Jung Han, Won Chan Joo, Jae Kyu Shin, Hyun Jin Kim, Soo Heung Chae; J Korean Endocr Soc. 1999;14(2):293-300. Published online January 1, 2001

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Abstract PDF: The Changes of soluble Fas levels in Patients with Autoimmune Thyroid Diseases BACKGROUD: Apoptosis was observed in thyroid tissue from Hashimoto disease but not those from Graves disease. Recently Fas and Fas ligand interactions among thyrocytes were suggested to development of clinical hypothyroidism in Hashimoto disease.Soluble Fas produced as the form lacking the tranmembrane domain due to alternative splicing, is supposed to inhibit Fas-Fas ligand interaction and blocks Fas mediated apoptosis. METHODS: In tbis study, we measured serum soluble Fas to determine the possible involvement of this molecule in the autoimmune thyroid disease by enzyme linked immunosorbant assay in 29 patients with Graves disease, 30 patients with Hashimotos disease and 19 normal controls. RESULTS: Compared with normal subjeets (4.26 +/- 1.00 U/mL), soluble Fas was not increased in patients with Graves disease (4.23 +/- 1.14 U/mL, p>0.05) but it was increased in throtoxic Graves patients (4.70 +/- 1.26 U/mL, p<0.05) compared to euthyroid Graves (3.72 +/- 0.73 U/mL, p<0.05) and normal subjects (4.26 +/- 1.00 U/mL, p<0.05). The euthyroid and hypothyroid patients with Hashimoto disease showed low soluble Fas levels, 2.94 +/- 0.54 U/mL and 2.74 U/mL, respectively compare to the patients with Graves disease and normal subjects. The thyroid hormone levels to (T3 T4 and free T4) showed positive correlation with the serum titers of antithyroid autoantibodies, antithyroglobuin antibodies, antiperoxidase antibodies and thyrotropin binding inhibitor immunoglobulins. CONCLUSION: We found that the patients with thyrotoxic Graves disease had increased level of serum soluble Fas and the patients with Hashimoto disease showed low levels of soluble Fas compared to normal controls. Increased soluble Fas in Graves disease suggests increased expression of alternatively spliced Fas mRNA variant and decreased soluble Fas in Hashimoto disease suggests decreased Fas mRNA variant and increased full length membrane Fas, so these findings are related to the promotion of apoptosis of thyroid cells during autoimmune reaction in Hashimotos disease.

Prevalence of Thyrotoxicosis and Hypothyroidism in the Subjects for Health Check-Up.: Jae Hoon Chung, Byoung Joon Kim, Yun Ho Choi, Myung Hee Shin, Sung Hoon Kim, Yong Ki Min, Myung Sik Lee, Moon Gyu Lee, Kwang Won Kim; J Korean Endocr Soc. 1999;14(2):301-313. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The prevalence of ovat hyperthyroidism ar hypothyroidism has been estimated up to 5% in the general populatian. Subclinical hyperthyroidism and subclinical hypothyroidism have pevalences of approximately 1% and 6%, ectively. The prevalence of hypothyroidism may be associated with excessive intake of iodine in iodine sufficient areas. Therefore, we assumed the prevalence of thyroid dysfunction in Karea might be different from those af Western cauntries. However, thete have been no surveys to examine the prevalence of thyroid dysfunction in Karea. We performed the study to investigate the prevalence of thyrotoxicosis and hypothyroidism in Korean adults. METHODS: This study was performed in 15019 subjects (8275 men, 6744 women; between 17 and 87 years of age) visited in health promotion center of Samsung Medical Center for 12 months in 1996. Serum T3, T4, and TSH concentrations were measured with RIA or IRMA using commercial kits. History of thyroid dysfunction and current medication were obtained from medical records. The criteria for thyrotoxicosis were TSH level below than 0.30 mU/L and increased T3 or T4 levels (T3 > 3.1 nmol/L or T4 > 152 nmol/L). Patients who had TSH level above than 5.0 mU/L and T4 level below than 77 nmol/L met the criteria for hypothyroidism. RESULTS: The prevalence of thyrotoxicosis was 5.5/1000 population (men 3.6/1000, women 7.7/1000) with peak prevalence in fifth decade. The prevalence of previously undiagnosed thyrotoxicosis was 4.0/1000 (men 2.9/1000, women 5.3/1000). The prevalence of hypothyroidism was 2.8/1000 population (men 1.1/1000, women 4.9/1000) with peak prevalence in seventh decade. The prevalence of previously undiagnosed hypothyroidism was 1.6/1000 (men 0.6/1000, women 2.S/1000). The prevalence of subclinical thyrotoxicosis was 12.4/1000 population (men 11.8/1000, women 13.0/1000). The prevalence of subclinical hypothyroidism was 18.2/1000 population (men 11.2/1000, women 26.7/1000) which frequency was increased with age. CONCLUSION: Although the prevalence of thyrotoxicosis and hypothyroidism was not significantly different from those of other countries, it was lower than expected and female preponderance is not significant. The prevalence of subclinical thyrotoxicosis and subclinical hypothyroidism was lower than those of other countries. The prevalence of subclinical hypothyroidism was higher in women and old ages. (J Kor Soc Endecrinol 14:301~313, 1999)

Allelotyping and Comparative Genomin Hybridization Studies in Papillary Thyroid Carcinomas and Follicular Adenomas.: Il Min Ahn, Eun Sook Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong, Kyung Yub Gong, Jin Yub Kim, Sung Bae Kim, Sang Hee Kim, Sung Jin Lee, Jung Hee Han, Kwan Ja Jee; J Korean Endocr Soc. 1999;14(2):314-322. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In our previous study, the prevalence of the known causes of thyroid tumorigenesis was relatively rare in Korean population, suggesting genetic and environmental differences exist. Screening of genetic alteration in papillary thyroid carcinoma(PTC) and follicular adenoma(FA) in whole genomic scale was needed prior to search on individual genes of possible causes. METHODS: Ten cases of PTC without ret/PTC-I, -2, -3 rearrangement and 5 cases of follicular adenoma were included in the study of microsatellite marker allelotyping. Sixty two microsatellite markers available, were chosen to cover the known sites of loss of heterozygosity(LOH) involved in thyroid tumors, tumor suppressor genes and terminal portion of each chromosomes. PCR was performed on tumor DNA and leukocytes DNA from each patient with MDE gel electrophoresis to detect LOH. Same specitnens as above, 3 case of normal thyroid tissues and NPA, ARO cell lines were included in the study of comparative genomic hybridization(CGH). Tumor and control DNAs were hybridized to metaphase chromosome with differential stainings with fluorescein and rhoda-mine-dUTP. Obtained results were analyzed by multicolor fluorescence computer assisted image analyzer. RESULTS: In allelotyping, LOH were detected in 5 cases of PTC, 2 cases on D10S1435, 1 case each on D2S1780, DSS1099, D11S1986, D16S539, 1 case of PTC revealed LOH on DSS1099, D11S1986. In FA, LOH were detected in 3 cases on D1S534, D1S226, Dl 1S907, D22S683, DXS9807. In CGH, Xp addition was noticed in 1 case of PTC, 12q and 10p addition was noticed in 1 case each, 16q deletion and 17q addition in 1 case of FA. CONCLUSION: No hot spot of LOH was noticed in microsatellite marker allelotyping, neither of common chromosomal change in CGH study suggesting unbalanced translocation or gene amplification more than 5-10 Mb may be involved in the genetic alteration of PTC and FA.

Comparosin of Pretreatment and Postreatment Whole Body Iodine-131 Scans in Patients with Differentiated Thyroid Carcinoma.: Eun Sook Kim, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon; J Korean Endocr Soc. 1999;14(2):323-329. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Whole body 131I scan is routinely performed in the postoperative evaluation of patients with differentiated thyroid carcinoma to detect recurrence and functioning metastasis. Previous reports suggested that posttreatment whole body scan had higher rate of detecting metastatic lesions that were not visualized by pretreatment images. We observed the frequency of discordance of the two scans and analysed the clinical significances. METHODS: Forty-one patients with differentiated thyroid carcinoma underwent radioactive iodine-131 whole body scans after administration of diagnostic dose (4 mCi) and then therapeutic dose (100~200 mCi of iodine-131). The median age of the patients was 46.9 +/- 15.7 years (range, 17~76). RESULTS: In 16 of the 41 patients (39.0%), pretreatment scan showed additional uptakes that were not seen in the pretreatment scan. Serum thyroglobulin was elevated in 13 of the 16 patients. Of the 22 patients who had been received radioactive iodine therapy previously, eight patients showed new additional lesions in the therapeutic scans but there was no significance according to the history of radioactive iodine therapy, Addisional uptakes after therapeutic dose were noted in neck area in 9 cases, lung in 2 cases, bone in 4 cases and mediastinum in one case. Diffuse hepatic uptake was definitely seen in 7 cases and there were 2 cases whose scans showed liver uptake without any thyroid uptake. CONCLUSION: Posttreatment whole body scan is more sensitive to detect residual tissues and metastasis compared to the usual pretreatment diagnostic whole body scan, and it is suggested that posttreatment whole body scan should be routinely performed after 'I therapy in patients with differentiated thyroid carcinoma for exact evaluation.

Effect of Radioactive Iodine Therapy in Patients with Scan-Negative, Thyroglobulin-Positive Thyroid Cancer.: Eun Sook Kim, Seok Jun Hong, Jin Yub Kim, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon, Ki Soo Kim, Sang Wook Kim; J Korean Endocr Soc. 1999;14(2):330-338. Published online January 1, 2001

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Abstract PDF: BACKGROUND
After total thyroidectomy the presence of detectable serum thyroglobulin(Tg) concentration is an index of residual or metastatic thyroid tissue and is usually well correlated with positive I whole body scan. However, it is not rare to find a patient with detectable serum Tg levels but without any uptake on I whole-body scan. At present it is not certain how to manage such patients. We performed whole body scan after administration of therapeutic dose of 131I to evaluate the usefulness of radioactive iodine therapy in the above setting. METHODS: Fifteen patients (4 males and 11 females, ranging in age from 17 to 74 years) were studied. They had been previously treated with total thyroidectomy for papillary thyroid cancer followed by therapy with 131I for ablation of their thyroid residue. Tg levels were determined by immunoradiometric assay method. 131I (100-200 mCi) therapy was administered and whole body scan was performed. 99mTc MIBI scans were taken in 9 patients. Follow up data of Tg were available in 12 patients at time interval of 6 12 months from the first study and treatment. RESULTS: Tg(on) levels of these patients were in a range of 2.2210 ng/mL (mean 36.1 +/- 59.1 ng/mL) and Tg(off) levels were 17.3 1,592 ng/mL (mean 197.3 +/- 400.3 ng/mL). After radioiodide therapy, Tg(on) levels were in 1.48.5 ng/mL (mean 11.0 +/- 13.5 ng/mL), Tg (off) were 11.9 478.0 ng/mL (mean 159.3 +/- 159.8 ng/mL). The Tg (on) levels were decreased significantly after RAI therapy, but Tg (off) levels had no significant difference, In 8 of the 15 patients (53.3%), posttreatment whole body scan showed definite positive uptakes which were not evident in pretreatment diagnostic scan. There were local recurrence in 3 cases, regional lymph node metastasis in 4 cases, and lung in I case. Diffuse hepatic uptake was definitely seen in 7 cases. The MIBI scan showed abnorml uptakes in 4 of 9 cases. CONCLUSION: The therapeutic usefulness of 100 to 200 mCi of 131I treatment in patients with 131I scan-negative and Tg-positive was unclear. And the MIBI scan was only partially effective. Further studies with other diagnostic and therapeutic approachs are required to evaluate the exact lesions and to improve prognosis.

A Comparison Technetium-99m and Iodine-123 Scan in Thyroid Hot Nodules.: Eun Sook Kim, Seok Jun Hong, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon, Ki Soo Kim; J Korean Endocr Soc. 1999;14(2):339-345. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Pertechnetate ( Tc) has been widely employed for thyroid imaging. While pertechnetate and radioiodide have usually similar results in identifying thyroid nodules, occasionally differences have been noted. We intended to observe that the thyroid nodules which appeared to be hot on pertechnetate and to compare them with the images by radioiodide. METHODS: 'I scan was performed to thirty-eight cases (mean age: 48.9 +/- 13.2) presenting as hot nodule on Tc scan. Thyroid function test and pathologic diagnosis were obtained in all patients. RESULTS: Of the 38 patients, 24 had euthyroidism, 13 had hyperthyroidism, and 1 had hypothyroidism. Thirty patients had adenomatous goiter, 4 papillary carcinoma, 3 Hashimotos thyroiditis, and 1 had HQrthle cell tumor. 28 of 38 patients showed similar images, but the remaining 10 patients(26.3%) revealed discordant images on Tc and 131I scan. Among the concordant cases, 23 had adenomatous goiter, 3 had papillary carcinoma, and 2 had Hashimotos thyroiditis. Among the discordant cases, 7 had adenomatous goiter, 1 had papillary carcinoma, 1 had Hashimotos thyroiditis, and 1 had HQrthle cell tumor. The incidence of malignancy was 10.7% of concordant cases, and 20% of discordant cases and was revealed statistically insignificant (p>0.05). CONCLUSION: We observed higher incidence of malignancy in patients presenting hot nodules on 99mTc scan than ever reported. Fine needle aspiration should be performed to all patients with hot nodules and the 'I scan would not be recommended for further diagnostic study.

Influence of Early Age at Menopause on Bone Mineral Density and Biochemical Bone Marker.: Young Joo Park, Chan Soo Shin, Do Joon Park, Jung Koo Kim, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee, Jae Hyun Kim, In Kyung Chung; J Korean Endocr Soc. 1999;14(2):346-354. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Among the various factors affecting bone mass and bone metabolism, aging and menopause play a major role. After the disappearance of the menstrual cycle, estrogen deficiency is the most important factor in bone loss. It is still unclear whether women with early menopause have a rate of bone loss different from women whose menopause has occurred later. Various biochemical bone markers are increased after menopause but it is still unclear whether women with early menopause have biochemical bone markers different from women whose menopause has occurred later. The aim of this study was to establish whether healthy women with early or normal menopause have different bone mass, biochemical bone markers and rates of bone loss. METHODS: Postmenopausal healthy women were divided into two groups according to their age at menopause(AAM): one group with AAM > 43 years, and the other group with AAM 50 years. Bone mass was measured using a dual energy X-ray absorptiometry(DEXA) in the lumbar, femur neck, femur trochanter, and Wards triangle. Serum levels of bone alkaline phosphatase and osteocalcin, and urine levels of calcium, deoxypyridinoline and type I collagen N-telopeptide were measured using a commercial kit. RESULTS: Age and body mass index in the early menopause group were different from those in the normal menopause group. All the bone mass and the biochemical bone markers in the early menopause group were not different from those in the normal menopause group. We selected 15 subjects from the two groups matched by age and BML Bone mass of femur neck in the early menopause group was lower than in the normal menopause group matched by age and BMI. Bone mass in lumbar, femur trochanter, and Wards triangle was lower in the early menopause group than in the normal menopause group, but the difference between the two groups was not significant. After adjusting years since menopause, we didnt find the difference of bone mass between the two groups. All the bone biochemical markers were not different in the two groups matched by age and BMI. CONCLUSION: Our data suggest that women with early menopause dont lose bone faster than women with normal menopause.

The Short-term Effects of Bone Marrow Transplantation on Bone Metabolism.: Soon Jib Yoo, Yoo Bae Ahn, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Ki Ho Song, Yoon Hee Choi, Bong Yeon Cha, Hye Soo Kim, Ki Won Oh, Sung Dae Moon, Sang Ah Jang, Chun Choo Kim; J Korean Endocr Soc. 1999;14(2):355-364. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The organ transplantation becomes the management of choice for many patients with chronic and life threatening heart, liver, kidney, bone marrow, and pancreatic diseases. A new set of side effects unique to this groups of patients has become recognized. Bone disease is one of these complications. It is well known that there is an interplay between the cells in the bone marrow and the surrounding bone tissue. Marrow stromal cells include the progenitors of the osteoblastic lineage are the sources of effector molecules that support and regulate both hematopoiesis and bone remodeling. But little is known about the effects of myeloablative treatment followed by bone marrow transplantation(BMT) on bone metabolism. METHODS: We have investigated prospectively in 29 patients undergoing BMT(4 autologous, 25 allogenic) for hematologic diseases(19 leukemia, 9 severe aplastic anemia, 1 myelodyspoietic syndrome). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and biochemical markers of bone turnover(osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen(ICTP)] were measured. The samples were collected before BMT and 1, 2, 3, 4, 12 weeks, 6 months and 1 year thereafter. Bone mineral density was measured with DEXA(Dual Energy X-ray Absorptiometry) before and after 1 year of BMT. RESULTS: 1. ICIP was progressively increased until 4 weeks after BMT when peak values were reached. And then decreased thereafter and basal values were regained after 1 year. Osteocalcin was progressively decreased until 3 weeks after BMT when nadir values were reached. And then increased thereafter and basal values were regained after 3 months. No distinct differences were observed in serum biochemical turnover marker between both sexes and between patients who received total body irradiation and those who did not. 2. Lumbar BMD was 2.1% decreased from 1.113 +/- 0.132 g/cm to 1.089 +/- 0.137 g/cm, and femoral BMD was 6.2% decreased fiom 1.078 +/- 0.156 g/cm to 1.011 +/- 0.157 g/cm. 3. 92% of the women (11/12) became menopausal manifested by high gonadotropin and low estradiol levels immediately after BMT. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and also increase in bone resorption, as mirrored by the biochemical markers in this study, might play a role for the post-BMT bone loss. Further studies over many patients with a longer follow up will be needed.

Serum Leptin in Cord Blood and Its Relation with Birth Weight and Metabolic Parameters.: Do Joon Park, Yun Yong Lee, Kyung Soo Park, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee, Gun Sang Park, Jong Kwan Jun, Bo Hyun Yoon; J Korean Endocr Soc. 1999;14(2):365-371. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the leptin is increased in obese adults even in children. This study investigated whether the serum leptin in cord blood was related to babys birth weight and metabolic parameters. METHODS: 71 pairs of singleton pregnancy babies and their mother were studied. Babies are classified in LGA (large for gestational age), AGA (appropriate for gestational age), SGA (small for gestational age) three groups. After delivery, cord blood and maternal venous blood samples were drawn. We measured the plasma leptin, insulin-like growth factor (IGF)-1, insulin and proinsulin in cord and maternal serum. RESULTS: The concentration of leptin from cord blood was increased in LGA babies and decreased in SGA babies compued with the level in AGA babies. There was positive correlatian (r=0.55, p<0.01) between the plasma leptin level in cord and birth weight. There were positive correlatian between both the plasma proinsulin (r=0.37, p<0.01) and IGF-1 (r=0.32, p<0.01) and birth weight, too. But there was no difference between female and male baby's cord blood leptin level. In multiple regression analysis, cord blood leptin level was found independent factor related to birth weight ( p=0.001) CONCLUDION : The plasma leptin, proinsulin and IGF-1 is correlates to the birth weight. These data provide evidence that leptin and proinsulin are highly related to the nutritional status already during the fetal periods, and effect on the intrauterine fetal growth.

Serum Leptin Levels in Patients with Thyroid Dysfunction.: Min hO Song, Young Kun Kim, Heung Kyu Ro, Hee Jung Han, Won Chan Joo, Jin Ho Won, Yoon Kim, Hyun Jin Kim, Soo Heung Chae; J Korean Endocr Soc. 1999;14(2):372-378. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Leptin, the product of ob gene, is an important circulating hormone for the regulation of homeostasis of body weight and enegy expenditure. There was a previous reports that thyroid hormone is one of regulating factors of leptin gene expression in vitro. The aim of this study was designed to evaluate the role of thyroid hormone levels in the regulation of circulating leptin concentrations in human. METHODS: A total 16S subjects were studied; 76 patients with Graves disease, 49 patients with Hashimoto disease and 43 control sujjects. The correlation between thryoid hormone and leptin levels were analyzed and serum leptin levels were compared among the groups which was classified by thyroid functional status. Serum leptin concentratios were measured by radioimmunoassay. RESULTS: There were no significant differences in serum leptin levels between the groups of control, Graves disease and Hashimoto disease. The hypothyroid groups of Graves disease which was induced by excessive antithyroid drug treatment showed significant low levels(5.6 +/-2.8 ng/mL) compared to control(9.6 +/- 5.2 ng/ml) and thyrotoxic groups(10.0 +/- 5,0 ng/mL) CONCLUSION: The hypothyroid patients showed low levels of serum leptin concentrations it may indicate that thyroid horrnone play a role in the appropriate secretion of leptin in human.

Endocrine Tumors of the Pancreas Secreting Multiple Hormones.: Young Cheol Kim, Oh Joong Kwon, Sun Hoe Kim, Yeo Kyu Yoon, Seung Keun Oh; J Korean Endocr Soc. 1999;14(2):379-391. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Endocrine pancreas tumor is a rare disease which incidence is less than 2% of all pancreatic tumors. But it comprises various types of tumor and usually secretes several hormones from one type of tumor although the patient with this tumor complains of sole symptom associated with only one hormone. The mechanism and clinical significance of multiple hormone secretion in the endocrine pancreas tumom are not yet clearly defined. METHODS: We analyzed retrospectively the clinicopathologic features of 20 cases which were operated at Seoul National University Hospital during the period between February 1989 and May 1998. RESULTS: The most common tumor was insulinoma (13 cases) and the second most common tumor was nonfunctioning tumor (6 cases). There was one case of somatostatinoma. Most of the patients with insulinoma complained of neuroglycopenic symptoms. There were 9 cases (45.0%) in which the tumors secreted more than two kinds of hormones, 7 cases in insulinoma, 2 cases in nonfunctioning tumors. Whether the tumor secreted multiple hormones was detected by the method of immunohistochemical staining. Though the tumors secreted more than two kinds of hormones, the patients with the tumors complained of symptoms which were associated with the cell type most strongly stained by immunohistochemical method. Whether or not the tumors secreted multiple hormones was not associated with the pathologic features such as tumor size, histologic patterns of the tumor, status of tumor cell differentiation and malignancy. CONCLUSION: From this results, we suggest that endocrine tumors of the pancreas secreted multiple hormones not by the mechanism of dedifferentiation from already differentiated endocrine cells but by the mechanism of neogenesis of multipotent islet stem cells. Since the relationship between the function of multiple hormone secretion in the endocrine pancreas tumors and islet stem cell would be significant, further study should be needed to find out the function of stem cells and application of stem cells to clinical use.

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