Endocrinology and Metabolism

Volume 12(4); December 1997

Original Articles

Molecular Neuroendocrine Regulation of GnRH and Its Recceptor.: Se Hyung Cho, Kyung Jin Kim; J Korean Endocr Soc. 1997;12(4):493-503. Published online January 1, 2001

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Abstract PDF: No abstract available.

Expression of Somatostat in Receptor in GH-Producing Pituitary to Adenoma.: Sung Yeon Kim; J Korean Endocr Soc. 1997;12(4):504-507. Published online January 1, 2001

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Abstract PDF: No abstract available.

Gene Expression of Somatostatin Receptor Subtype 2 and 5 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, Kook Ki Kim; J Korean Endocr Soc. 1997;12(4):508-517. Published online January 1, 2001

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Abstract PDF: BACKGROUND
SSTR2 and SSTR5 are most frequently observed in GH-secreting pituitary tumors, and SSTR5 is believed to be more specific to mammosomatotroph lineage. Octreotide binds with high affinity to those two types. There is no report that investigates the quantitative comparison of the two subtype gene expressions, and the correlation between their gene expressions and GH response to octreotide in GH-secreting pituitary adenomas. METHOD: GH response to octreotide was examined in 8 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were prepared from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gas gene. mRNAs of SSTR2 and SSTRS were quantitated by the comparative RT-PCR and in vitro transcription. RESULTS: The in vitro transcripts of SSTR2 and SSTR5 cDNA were detected in all tumors. The amount of SSTR transcripts was considerably variable between the tumors. The amount of SSTR5 transcript was significantly smaller than that of SSTR2 transcript (0.07+-0.02 vs. 0.87+-0.10), and they did not show any correlation . There was no signicant difference in sex, age, tumor size and grade, basal GH levels, and the GH responses to octreotide between the group with high and low SSTR gene expression. No significant correlation was found between the GH response to octreotide and the amount of SSTR2 transcript, wherease the amount of SSTR5 transcripts showed a tendency of negative correlation with the octreotide response. Tumors with gsp oncogene showed significantly higher response to octreotide than those without the oncogene. The amount of SSTRS transcript in gsp-positive tumors was significantly smaller than in gsp-negative tumors (0.03+-0.01 vs. 0.12+-0.03). CONCLUSION: These results suggest that SSTRS gene expression is lower than that of SSTR2 in GH-secreting adenomas. It is probably attributed to the binding of somatostatin to SSTR5 which has a higher affinity to the hypothalamic somatostatin, Tumors with gsp-oncogene is likely to express a higher density of SSTR5 than those without the oncogene.

Regulation of Estrogen Receptor mRNA in Rat Anterior Pituitary Gland.: Min Seok Chun, Duck Bae Park, Yong Bin Park, Kyung Yoon Kam, Chang Mi Kim, Kyung Ja Yoo; J Korean Endocr Soc. 1997;12(4):518-527. Published online January 1, 2001

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Abstract PDF: The estrogen receptor (ER) is present in a wide variety of mammalian tissues and is required for the physiological responses of estrogen, including estrogen-induced tissue-specific changes in gene expression. But most of our knowledge on the regulation of ER mRNA levels comes from in vivo steroid replacement experiments or cancer cell lines that express the ER. Thus the present study was attempted to determine 1) the anterior pituitary ER mRNA levels during rat estrous cycle 2) if estradiol itself directly modulates the ER mRNA levels in cultured rat anterior pituitary using RT-PCR method. In rats with 4 day estrous cycle, the ER mRNA levels in anterior pituitary gland reached to maximum at proestrus 11:00h just before serum estradiol concentration showed the highest. From then, the ER mRNA levels gradually declined during the rest of the proestrus. On the other hands, in cultured rat anterior pituitary cells, the ER mRNA levels were significantly decreased by the treatment of estradiol. These results indicate that the surge of estradiol was proceeded by the increase in pituitary ER mRNA levels during the proestrus and in cultured anterior pituitary cells, estrogen might be involved in the down-regulation of the ER mRNA levels.

Anticardiolipin Antibody in Graves' Disease.: Young Ki Song, Ki Soo Kim, Jung Hee Lee; J Korean Endocr Soc. 1997;12(4):528-532. Published online January 1, 2001

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Abstract PDF: BACKGROUND
S: Antiphospholipid antibodies which are frquently found in systemic lupus erythematosus and primary antiphospholipid syndrome are associated with recurrent abortions and thromboembolism. In this study the authors investigated whether antiphospholipid antibodies are found in Graves disease, a representative organ-specific autoimmune disease and what is the clinical implication of the antiphospholipid antibodies if they appear in Graves disease. METHODS: Anticardiolipin antibody and lupus anticoagulant activity were measured in 57 untreated hyperthyroid Graves patients. 42 euthyroid patients with thyroid nodules served as controls. RESULTS: Eight of the 57 patients with Graves disease had anticardiolipin antibody which was significantly more frequent than in control group. Six of the eight patients who had anticardiolipin antibody had IgM type antibody and two had IgG type antibody. All their antibody activity declined with several months of antithyroid drug therapy and finally disappeared when the patients became euthyroid. Presence of anticardiolipin antibody had no relationship with clinical events such as spontaneous abrtion and thromboembolism. CONCLUSION: Anticardiolipin antibody is frequently found in patients with Graves disease. They seem to appear as an epiphenomenon of autoimmunity and they seem not to have any clinical implications.

Expression of E-cadherin and a-catenin in Thyroid Carcinomas.: Sang Jin Kim, Min Chul Lee; J Korean Endocr Soc. 1997;12(4):533-540. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Cell-cell adhesion in tissue is mainly regulated by hornotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including a-and / 3-catenin. Loss of E-cadherin and catenin have been attributed a pathogenetic role in tumor invasion. METHODS: We examined the expression of E-cadherin and a-catenin in human thyroid carcinoma by immunohistochemistry. RESULTS: Normal tissue strongly expressed E-cadherin and a-catenin. However, E-cadherin and a-catenin expression were frequently reduced in thyroid carcinoma (E-cadherin: 62.5%, a-catenin: 81.3%). But the expression of E-cadherin and a-catenin in tumors with metastatic spreading were not different with tumors without metastasis. CONCLUSION: These results suggest that reduced E-eadherin and a-catenin expression may be a sensitive marker for disturbance in the adhesive function of the junctional complex, but further evaluation with more cases is needed for confirmation of the result of the same degree of expression in tumors with metastasis.

Clinical Report of Effects of Pre and Post-partum Thyroiditis (PPT).: Yong Wook Cho, Myung Seo Kang, Young Soo Cha, Jin Hwan Kook, Yoo Ri Kim, Pil Won Park, Wee Hyun Lee, Jung Eun Lim, Yo Won Cho; J Korean Endocr Soc. 1997;12(4):541-549. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Excessive iodine intake increases the occurrence of autoimmune thyroid disorders by enhancing immunogenecity of iodine-rich thyroglobulin, In Korea, most of postpartum women take a large amount of iodine-rich seaweed. Although the excessive iodine intake may affect the thyroid function, only a few reports were available concering iodine intake, especially on postpartum period. METHODS: A prospective study was undertaken in 146 of normal delivered postpartum women. Dietary intake and urinary excretion of iodine, serum T3, T4, TSH, anti-TPO Ab and anti-Tg Ab were measured before and 1, 6, 12 and 24 weeks after delivery. Iodine intake was analyzed by one-to-one interview using 24hr recall and food frequency questionnaire. RESULTS: 1. PPT was occurred in 6 (10.3%) postparturn women, It presented as hypothyroidism alone in 1 (16.7%), transient thyrotoxicosis followed by hypothyroidisrn in 3 (50.0%), and thyrotoxicosis alone in 2 (33.3%) of the follwed-up patients. 2. During pregnancy, no difference was found in age, serum T3, T4 and TSH between PPT and normal thyroid function group. 3. In PPT group, anti-TPO and anti-Tg Ab were significantly higher than those of normal thyroid function group during pregnancy, and their sensitivity for PPT was 40% and 33%, respectively. But there was no correlation between dietary iodine intake and the titer of thyroid auto-antibodies. 4. There was no correlation between pre and post-partum dietary iodine intake and occurrence of PPT. CONCLUSION: In Korea, the incidence of PPT was slightly higher than other nations. The sensitivity of thyroid auto-antibodies was too low to use for prediction of PPT. Pre and post-partum iodine intake had no effect on the occurrence of PPT and post-partum thyroid function.

Prevalence of Autoimmune Thyroid Disease and Correlation Between Thyroid Autoantibody and Acetylcholine Receptor Antibody in Myasthenia Gravis Patients.: In Kyu Lee, Sung Rae Cho, Chan Kyu Park, Sung Jin Nam, Choo Sung Kim, Seung Yub Han, Jung Geun Lim, Sang Do Lee, Young Chun Park; J Korean Endocr Soc. 1997;12(4):550-556. Published online January 1, 2001

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Abstract PDF: BACKGROUND
There were several reports that thyroid autoimrnune disease commonly found in myasthenia gravis patients. We performed this study to determine the prevalence of thyroid autoimmune disease as well as analyze correlation between acetylcholine receptor antibody and various thyroid autoantibadies among the myasthenia gravis patients in Korea. METHOD: The patient group, 48 patients, diagnosed as myasthenia gravis from January 1985 to December 1995 at the department of Neurology, Internal medicine at Dongsan Medical Center was compaired to the control group, 40 patients, with no age and sex difference from the patient group. The samples were collected from both group for the measure of the values of acetylcholine receptor antibody, thyroid autoantibody and thyroid hormones. RESULT: 1) The values of acetylcholine receptor antibody in myasthenia gravis group and control group were 5.78+-0.7nM and 0.05+-0.06nM respectively. Of 48 patients with myasthenia gravis, 38 patients have been measured acetylcholine receptor antibody value > 0.5nM, Their mean average value was 7.24+-0.66nM. 2) The severe myasthenia gravis group with value of acetylcholine receptor antibody 0.5nM and severe myasthenia gravis group with value of acetylcholine receptor antibody 0.5nM showed thyroglobulin antibody value of 159.6+-79.91IU/mL versus 56.86+-32.99IU/mL. also thyroid microsomal antibody value showed 159.0+-79.9IU/mL and 23.633+-0.19IU/mL respectively. 3) Of 48 myasthenia gravis patients, 12 patients (24%) had high value of antithyroglobulin antibody or anti-microsomal antibody and 5 patients (10%) had both antibodies at the same times. In contrast, only 3 patients (8%) were observed with high value of either one of antibodies. Patient with both antibodies was not observed in normal control group. CONCLUSION: According to the datas we have obtained, appearence of the thyroid autoantibody is significantly greater in severe myasthenia gravis group than normal control group. Therefore it is suggested that the prevalence of thyroid autoimmune disease is higher in severe myasthenia gravis group than mild myasthenia gravis group or normal control group.

Effects of Thyroid Hormone on Preduction of Interleukin-6 and Interleukin-11 in Human Bone Marrow Stromal Cells.: Chul Hee Kim, Dong Kwan Kim, Hong Kyu Kim, Young Ki Song, Ki Soo Kim; J Korean Endocr Soc. 1997;12(4):557-564. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well known that excessive thyroid hormone in the body is associated with bone loss. However, the mechanism by which thyroid hormone affects bone cell metabolism remains unclear. It has been shown that thyroid hormones stimulate osteoclastic bone resorption indirectly via some unknown mediators secreted by osteoblasts, This study was undertaken to determine if interleukin-6 (IL-6) or interleukin-11 (IL-l1) could be the mediator (s) of thyroid hormone-induced bone loss. METHODS: We treated primary cultured human bone rnarrow stromal cells with 3,5,3-triiodo-thyronine (T) and measured basal and interleukin-l (IL-1)-stimulated IL-6/IL-ll production. We also investigated the possible modulating effect of 17B-estradiol (17B-E2.) on thyroid hormone action. RESULTS: T3 at 10 (-12) ~ 10 (-8) M concentration, significantly increased the basal IL-6 production in a dose-dependent manner, and also potentiated the stimulatory effect of IL-1 on IL-6 production. However, T failed to elicit a detectable effect on basal or IL-1-stimulated IL-11 production. Treat#ment with l7B-E2. inhibited IL-1-stimulated IL-6 production, but the effects of T3 on IL-6 production were not affected by 17/B-E. CONCLUSION: These results suggest that thyroid hormone may increase bone resorption by increasing basal IL-6 production and potentiating IL-1-induced IL-6 production from osteoblast-lineage cells, and these effects were independent of estrogen status.

Serum Fluoride Level in Normal Adult Women and Changes in Serum Fluoride Level after Disodium Monofluorophosphate Administration.: Hyun Koo Yoon, Mi Sun Jung, In Kul Moon, Sang Woo Kim, Ho Yeon Chung, Ki Ok Han, Hak Chul Jang, In Kwon Han, Hun Ki Min; J Korean Endocr Soc. 1997;12(4):565-570. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Since the morning fluoride level of 10 uM is recommended for adults patients being treated for osteoporosis so far, measurement of serum fluoride level is important to detect abnormally high levels or to detect levels below the therapeutic windows. Aims of this study are to determine the normal range of serum ionic fluoride levels in Korean female adults (from 5th to 7th decade), and to evaluate the in vivo fluoride pharmacokinetics of monofluorophosphate in Korean adults. METHODS: Serum level of fluoride was measured from blood samples of 72 female subjects (age 43-69years) using an ion selective electrode. For pharrnacokinetics of monofluorophosphate-calcium (MFP-Ca), 6 subjects (age 27~45 years) were included to be withdrawn the blood hourly for the first S hours and the blood was withdrawn at 24 hours after a single dose of MFP-Ca. RESULTS: Mean level of serum fluoride was 1.64+-0.12uM in 5th, 6th, 7th decades adults, and there was no difference of serum fluoride levels among age groups. Peak serum fluoride level exhibited 5.02+-0.67pM, and returned to basal level on 24 hours after a single dose of MFP-Ca. CONCLUSION: This study shows that mean serutn fluoride of Korean female adults (from 5th to 7th decade) is not different from that of other reports, and a single dose of MFP-Ca does not cause serum fluoride levels above the recommended therapeutic windows of 5-10uM for 24 hours.

Randomized Controlled Trial

The Benificial Effects of Growth Hormone Therapy with Diet Restriction in Obese Adults.: Sung Kil Lim, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Eun Sook Kim, Jae Ho Shin, Kyung Rae Kim, Soo Yeon Nam; J Korean Endocr Soc. 1997;12(4):571-583. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Carolic restriction as a treatment for obesity causes catabolism of body protein stores and produces negative nitrogen balance. GH administration causes acceleration of lipolysis and promotion of nitrogen conservation. We evaluated the effects of GH treatment and caloric restriction on lipolysis, anabolic effects and body composition in obese subjects. METHODS: 24 obese (20% over IBW) subjects (22 women and 2 men; 22-46yr old) were fed a diet of 25kcal/kg IBW with 1.2g protein/kg IBW daily during treatment. The subjects were assigned at random to either treatment with recombinent human GH (n=12, 0.06U/kg IBW every other day) or placebo (n 12, vehicle injection) for 12 weeks. Body fat was assessed by impedence and abdominal fat, visceral fat area at the umbilicus level and muscle area of mid thigh level were measured using computed tomography. RESULTS: Fraction of body weight lost as fat lost was significantly greater in GH treatment than in placebo group (1.21+-0.48%/kg, vs 0.52+-0.28%/kg, p0.05). GH treatment caused significant decrease in visceral fat area (35.3% vs 28.5%, p<0.05). In placebo group, there were significant loss of muscle area (-4.8 +-2.6cm ) and lean body mass (-2.62 +-1.51kg) after treatment. In contrast, GH treatment group had more increase in muscle area (3.5+-2.3cm ) and lean body mass (1.13 +-1.04kg) and positive nitrogen balance (1.81+-4.06g/day). GH injections cuased a 1.6-fold increase in IGF-I, despite caloric restriction. GH responses to L-dopa stimulation were blunted in all subjects and GH responses were increased after treatment. Both group showed hyperinsulinemia during oral glucose tolerance test (OGTT), and after treatment, they had decreased in insulin secretion. However, GH treatmnent group had not significant decrease, because GH might induce insulin resistance. FFA response areas during OGTT markedly decreased after treatment in both group. In GH treatment group, more decrease of FFA responses might result from the antilipolytic effect by higher level of insulin or more decrease in amount of fat. CONCLUSION: This study has demonstrated that in obese subjects fed hypocaloric diet, GH accelerates body fat loss and exerts anabolic effects.

Case Reports

A Case of Partial Hypopituitarism after Recovery from Korean Hemorrhagic Fever.: Yeo Joo Kim, Mi Rim Kim, Moon Seok Nam, Yong Sung Kim, Sung Ki Kim, Sung Kwon Bae; J Korean Endocr Soc. 1997;12(4):584-588. Published online January 1, 2001

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Abstract PDF: Heorrhage and infarct-like necrosis of anterior lobe of the pituitary gland is one of the characteristic pathologic findings of the autopsied cases of Korean Hemorrhagic Fever (KHF) patients, but there has been rare reports of hypopituitarism in patients with KHF. Recently we have experienced a patient with hyponatremia who had recovered from KHF. He was admitted to our hospital due to nausea, vomiting, and epigastric discornfort. To determine the function of the anterior pituitary gland, hormonal levels of target galnds and pituitary gland were measured, and combined pituitary stimulation test was performed. ACTH, GH, and prolactin deficiency were confirmed by combined pituitary stimulation test in this patient. There was no evidence of hypothalamic or other pituitary diseases by brain MRI. Our experience shows that KHF can be a cause of hypopituitarism and these findings should alert physicians the possibility of hypopituitarisrn in patients who had recovered from KHF.

A Case of Piouitary Hyperplasia with Retardation due to Primary Hypothyroidism.: Hong Seung Kim, Choon Hee Chung, Young Goo Shin, Bong Ki Lee; J Korean Endocr Soc. 1997;12(4):589-595. Published online January 1, 2001

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Abstract PDF: Primary hypothyroidism can result in reactive enlargement of the pituitary gland which is indistinguishable from primary pituitary lesions in clinical presentation and on magnetic resonance imaging. A 17-year-old girl came to the hospital due to short stature, general weakness and galac-torrhea. The magnetic resonance imaging (MRI) study showed pitutary enlargement. The hormone study showed hyperprolactinemia, decreased basal growth hormone level and primary hypothyroi-dism. By thyroid replacement therapy only, mass was successfully regressed on follow up MRI after 4 months, and growth acceleration could be achieved.

A Case of Central Diabetes Insipidus Caused by Metastatin Malignant Lymphoma.: Sung Kil Lim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Hyun Soo Kim, Kyung Rae Kim, Yoo Mi Lee, Yong Suk Yoon, Suk Ho Kwon, Jae Hyun Nam, Sang Hak Lee; J Korean Endocr Soc. 1997;12(4):596-601. Published online January 1, 2001

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Abstract PDF: The causes of central diabetes insipidus (CDI) are numerous; some primary cases are idiopathic while most secondary cases are surgically induced or the result of tumor. The frequency of metastatic tumor as a cause of DI is 6% to 20% of cases, Variety of malignancies including breast, lung, colon, prostate cancer, and leukemia/lymphoma have been reported to metastasize to the pituitary, although most patients are asymptomatic. Clinical manifestations of pituitary metastases include anterior pituitary failure, visual disturbance, and extraocular muscle weakness. DI is the most common clinical manifestation of hypothalamic-pituitary axis (HPA) metastases. Anatomical basis far this clinical picture is that most metastases occur in the posterior lobe. We report on a 35-year-old male patient with meningeal involvement of malignant lymphoma that was thought to be associated with DI. Confirmation of primary malignancy was made by biopsy at site of cervical lymph node and tonsil, Pituitary involvement was suspected on brain MRI, and satisfactory symptornatic relief was obtained with vasopressin. Because of the progres-sion of underlying lymphorna that has shown no response to combined anticancer chemotherapy, the patient expired on 60th hospital day.

A Case of Pituitary Metastasis of Lung Presenting as Diabetes Insipidus.: Hong Seung Kim, Choon Hee Chung, Mee Yeon Cho, Yun Mi Kim, Kye Chul Shin, Do Hoon Kim, Kwang Sun Song; J Korean Endocr Soc. 1997;12(4):602-608. Published online January 1, 2001

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Abstract PDF: This is a case report of a 61 years old man with suprasellar and pituitary metastasis from bronchogenic adenocarcinoma who developed polyuria and polydipsia. The clinical diagnosis has been made by bronchoscopy with washing cytology, biopsy of cervical lymph node, and brain MRI scan. Brain MRI scan showed metastatic tumor in the suprasellar area and pituitary gland with invasion of pituitary stalk. Light microscopic findings revealed adenocarcinoma in bronchoscopic washing cytology, and metastatic adenocarcinoma in the cervical lymph node. The combined pituitary stimulation test showed decreased reserve capacity of anterior pituitary hormones. And the water deprivation test also showed complete central diabetes inspidus. We report a case of suprasellar and pituitary metastasis from bronchogenic adenocarcinoma with a review of the literature.

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