Endocrinology and Metabolism

Volume 10(3); September 1994

Review Article

Vitamin D Receptor Polymorphism and Genotype Hypothesis of Osteoporosis.: Sung Kil Lim; J Korean Endocr Soc. 1994;10(3):183-186. Published online November 6, 2019

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Abstract PDF: No abstract available.

Editorial

Clinical Significance of Hyperinsulinsism - Diagnosis of Insulinoma.: Sung Woo Park; J Korean Endocr Soc. 1994;10(3):187-190. Published online November 6, 2019

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Abstract PDF: No abstract available.

Original Articles

Clinical Significance of Thyrotropin Measurement as a Screening Test in Ambulatory Patients.: Young Kee Shong, Hong Kyu Kim, Ghi Su Kim, Dae Hyuk Moon; J Korean Endocr Soc. 1994;10(3):191-199. Published online November 6, 2019

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Abstract PDF: The objective of this study is to determine the clinical significance of thyrotropin(TSH) measurement as a screening test in ambulatory patients. One hundred and nintynine patients with abnormal TSH levels detected at routine examinations were studied. The patients were examined and histories about the recent medications and nonthyroidal illness were taken. Additional thyroid tests were done including measuments of total T_3, free T_4, antithyroid autoantibodies, thyroid scan and radioiodine uptake. Of the total 199 patients, 107(54.7%) had thyroid diseases. 49 out of 101 patients with subnormal TSH had thyroid diseases, and the remainder had supressed TSH due to medications, associated nonthyroidal illness, and normal variations. 58 out of 99 patients with elevated TSH had thyroid diseases. Of those 47 patients whose TSH level was below 0.05 mIU/L, functional sensitivity of TSH assay in our laboratory, 37 had thyroid diseases. Of those 19 patients whose TSH level was above 7.0mIU/L, two times of upper normal limit, all had thyroid iseases.Simultaneous measurement of free T_4 disclosed 50(25.1%) out of total 199 patients with abnormal TSH levels had abnormal free T_4 values which is regarded as evidence of clinical thyroid dysfunction. In summary, a single measurement of TSH level alone seems to have high sensitivity but low specificity. Simultaneous measurement of free T_4 can reasonably compensate the low specificity of TSH measurement. In case of ambulatory patients without significant nonthyroidal illness, TSH values below functional sensitivity or above twice upper normal limit may predict thyroid disease and dysfunction with reasonable specificity.

Identification of TPA - Response Element (TRE) in the Rat Thyrotropin - Releasing Hormone (TRH) Gene.: Woon Won Jung, Young Kil Choi, In Myung Yang, Kwang Sik Seo, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Seung Joon Park; J Korean Endocr Soc. 1994;10(3):200-213. Published online November 6, 2019

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Abstract PDF: There are two potential imperfect copies of the TRE consensus sequence between -47 and -113bp position on 5' upstream of the rat TRH gene. The upstream element(5'-TGcCgTCA-3') is located between -101 bp and -94 bp, and the downstream element(5'-TGAcCTCA-3') is positioned between -59bp and -52bp relative to the stranscription start site. The downstream variant differs from the consensus sequence of TRE(AP-1)(5'-TGACTCA-3'), by addition of one nucleotide. As there is no direct evidence that TPA stimulates the transcription of rat TRH gene, and there is no study to define TRE of the rat TRH gene, we performed Northern blot assay, transient gene expression study and gel shift assay to identify TRE. TRH mRNA expression of CA77 cells was increased about 2-2.5 fold 30 min after TPA stimulation. When PC12 cells were stimulated by TPA after transfection of the plasmids containing serially deleted 5'upstream of the rat TRH gene ligated to luciferase gene, the transcription of luciferase gene was increased more than 3.2 fold with the plasmid pTRH(-600/84)Luc and pTRH(-113/84)Luc. However, the transcriptional activation was remarkably decreased less than 1.6 fold with pTRH(-77/84)Luc, pTRH(-47/84)Luc, and pTRH(6/84)Luc. The plasmid containing the sequence of -108/-79 did not show any significant activation in both of basal and TPA-stimulated transcription, whereas the plasmid containing the sequence of -70/-41 showed a slight but significant transcriptional activation by TPA. The plasmid containing the sequence of -114/-47 showed remarkable increase in basal transcription and TPA induced transcription of luciferase gene. Gel shift assay revealed that the oligonucleotides spanning -108/-79 and -70/-41 bound to c-Jun, whereas the oligonucleotides spanning -40/1, 1/30, 31/60, 61/84 did not bind. The oligonucleotide of -70/-41 bound to c-Jun with higher affinity compared to that of -108/-79. The one base pair mutant of -70/-41(deletion of C from the middle of TGACCTCA) bound to c-Jun with higher affinity, whereas the one base pair replaced mutant(C to G) bound with lower affinity compared to the wild type oligonucleotide. These results suggest that the rat TRH gene expression is stimulated by TPA to a smaller degree compared to that of other genes, and the two elements act cooperatively as TRE. The downstream TRE variant is mainly responsible for TPA response and c-Jun binding, and the upstream variant play a permissive role for transcriptional activation. The addition of one nucleotide C in the downstream element may be responsible for the relatively lower response of the rat TRH gene to TPA.

Changes of Interleutin-6 Level Ofter Treatment of Radioactive Iodine in Graves' Disease.: Keun Yong Park; J Korean Endocr Soc. 1994;10(3):214-219. Published online November 6, 2019

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Abstract PDF: Interleukin-6(IL-6) is a cytokine secreted from lymphocytes or non-lymphoid cell(monocyte, fibroblast, osteoblast, vascular endothelial cell, or synoviocytes). Increased serum IL-6 concentrations have recently been reported in patients with subacute thyroiditis, possibly because of cytokine release damaged thyroid cells. In this study, IL-6 levels serum T_3, T_4, Thyroglobulin(Tg) and TSH were determined by an radioimmunoassay method in 14 patients treated with radioactive iodine(10mci) for Graves' disease. IL-6 levels were as follows: 23.9+-0.8 fmol/ml(at baseline), 25.4+-1.1 fmol/ml(1hour), 24.7+-0.6 fmol/ml(24hours), 76.8+-2.0 fmol/ml(48hours), 22.8+-0.5 fmol/ml(72hours). There was significant increase in IL-6 values at 48hours after RAI treatment(p<0.01). Serum Tg, T_3 and T_4 also increased after RAI treatment, but no significant correlation could be demonstrated with the increase in L-6. The results of this study support the concept that IL-6 can be regarded as a useful marker of thyroid-destructive processes.

The Effect of Tumor Necrosis Factor - α on the Thyroglobulin Synthesis and TSH Action in Cultured Porcine Thyroid Cells.: Jae Wha Jo, Eun Jig Lee, Moon Suk Nam, Su Youn Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim; J Korean Endocr Soc. 1994;10(3):220-228. Published online November 6, 2019

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Abstract PDF: Abnormal thyroid function is seen in a wide variety of patients with acute and chronic nonthyroidal-illness, consisting of reduction in both thyroid function and peripheral T_4 to T_3 conversion including decreased serum thyroxin(T_4), decreased triiodothyronine and normal or slightly increased serum TSH. Recently increasing awareness of the role of tumor necrosis factor-alpha(TNF-alpha) in systemic illness led us to consider a possible contribution of TNF-alpha to thyroid dysfunction in this setting. So we hypothesized that TNF-alpha might affect the function of the thyroid gland. We, therefore, explored the effects of TNF-alpha on the cultured porcine thyroid cells in TSH-stimulated and TSH-nonstimulated conditions. Primarily cultured porcine thyroid cells were incubated with various concentrations(-500pg/ml) of recombinant buman TNF-alpha and bTSH(1mu/ml), with measurement of secreted thyroglobulin(Tg) and cyclic AMP(c-AMP) as the end points of stimulation, and produced intracellular Tg by pulse-labelling. TNF-alpha significantly inhibited TSH-stimulated intracellular Tg synthesis and extracellar Tg secretion at 200 and 500pg/ml concentration. TNF-alpha didn't affect c-AMP production at any concentration tested. So we conclude that increased in serum TNF-alpha may be responsible for reduced thyroid function in patients with acute and chronic nonthyroidal-illness.

Changes in Thyrotropin Receptor Blocking Antibody after Antithyroid drug Administration to Patients with Atrophic Autoimmune Thyroiditis (Primary Myxedema).: Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Jae Hoon Chung, Chang Soon Koh, Chan Soo Shin, Won Bae Kim; J Korean Endocr Soc. 1994;10(3):229-241. Published online November 6, 2019

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Abstract PDF: It is well Known that antithyroid drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels including thyroid stimulating antibodies(TSAb) in most patients suggesting the immunosuppressive or immunomodulating effects of antithyroid drugs. In the context of view that thyrotropin receptor blocking antibody may play an important pathogenetic role at least in some patients with primary myxedema(chronic atrophic autoimmune thyroiditis), antithyroid drug treatment in these patients might be beneficial to disease course. To evaluate the effect of antithyroid drug on the thyrotropin receptor blocking antibody levels, we serially measured thyrotropin-binding inhibitor immunoglobulins(TBII) and thyroid stimulation blocking antibodies(TSBAb) using FRTL-5 cells, antimicrosomal- and antithyroglobulin antibody activities in 7 patients with primary myedema who have blocking TSH receptor antibodies during 6 months of methimazole(MMI, 40mg/day) administration. TBII and TSBAb activities did not change after MMI, but one of them showed stepwise decrease and disappearance of TBII and TSBAb activities. Antimicrosomal- and antithyroglobulin antibody activities decreased significantly after 3 months of MMI administration in those patients. These results suggest a minimal effect of antithyroid drug treatment on the level of thyrotropin receptor blocking antibodies. Persistence of thyrotropin receptor blocking antibodies despite of the decrease in antimicrosomal and antithyroglobulin antibodies might suggest that blocking TSH receptor antibodies of primary myxedema is produced mainly in extrathyroidal tissue in contrast to the thyroid stimulating antibodies of Graves' disease. One patient, whose blocking antibody have disappeared after MMI treatment, is under observation to see if she will remain in remission of hypothyroidism.

The Effect of Tumor Necrosis Factor - α on Extra Thyroidal Conversion of T4 to T3 in Slices and Extracts of Porcine Liver and Kidney.: Jae Wha Jo, Moon Suk Nam, Su Youn Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Eun Jig Lee; J Korean Endocr Soc. 1994;10(3):242-248. Published online November 6, 2019

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Abstract PDF: Abnormal thyroid function is seen in a wide variety of patients with acute and chronic nonthyroidal-illness, consisting of reduction in both thyroid function and peripheral T_4 to T_3 conversion including decreased serum thyroxin(T_4), decreased triiodothyronine and normal or slightly increased serum TSH. Recently increasing awareness of the role tumor necrosis factor-alpha(TNF-alpha) in systemic illness led us to consider a possible contribution of TNF-alpha to thyroid dysfunction in this setting. So we hypothesized that TNF-alpha might affect peripheral conversion of T_4 to T_3. We, therefore, explored the effects of TNF-alpha in slices and extracts of porcine liver and kidney. Thyroxine(T_4, 5ug/ml) was incubated in 0.15M phosphate buffer(PH 7.4) with slices(approximately 0.3 g-equivalent of tissue) and extracts(approximately 0.23 g-equivalent of tissue) of porcine liver and kidney with various concentrations(0-500pg/ml) of recombinant human TNF-alpha for 2 hours at 37 degree, and the T_3 generated during incubation was measured by radioimmunoassay of an ethanol extracts of the extracts and the homogenates of the slices. The slices produced more T_3 than extracts and the kidney was more active than the liver. TNF-alpha inhibited T_4 to T_3 conversion in dose-dependent manner in slices and extracts of porcine liver and kidney. Our data suggest that TNF-alpha have inhibitory effect of T_4 to T_3 conversion in liver and kidney(J Kor Soc Endocrinol 10: 242-248, 1995).

Study on Restriction Fragment Length Polymorphisms of Vitamin - D Receptor Gene in relation to Bone Mineral Density and Bone Markers in Pre - and Postmenopausal Korean Women.: Myung Hee Yoo, Dong Won Byun, Kyo Il Suh, Guk Bae Kim, Sang Woo Kim, Ihn Gul Moon, In Kwon Han; J Korean Endocr Soc. 1994;10(3):249-261. Published online November 6, 2019

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Abstract PDF: Osteoporosis is now a major health problem because of the increasing elderly population and related osteoporosis fractures. Recently, it has been suggested that lower bone mass with/and high bone turnover rate is considered to be important in the developing of osteoporosis, and so there has been many efforts to identify the risk factors which is considered to cause lower bone mass and high bone turnover.Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover and its synthesis is induced by calcitriol(the active form of vitamine-D) through the vitamine-D receptor(VDR) and a specific vitamine D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under the strong genetic influences and may reflect allelic variation in VDR gene. Therefore, the present study were designed to find the relationships among the polymorphisms of Vitamine-D receptor gene, bone mineral density and bone markers. We analysed the restriction fragment length polymorphisms of VDR gene with Bsm I endonuclease enzyme in relation to bone mineral density by using DEXA(dual energy X-ray absorptiometry, QDR-2000) and bone markers, especially serum osteocalcin concentrations in 356 pre- and postmenopausal Korean women.The frequence of RFLPs of VDR gene is 3.3% in BB type, 10.1% in Bb type, 86.6% in bb type. The concentrations of osteocalcin, alkaline phosphatase, procollagen-C and urinary deoxypyridinoline/creatinine were found to be higher in postmenopausal than premenopausal women and the levels of BMD were lower in postmenopausal than premenopausal women. The BB type, which is known to have a strong genetic determinant, is less frequently encountered in Korean women and does not correlate with levels of bone markers and bone mineral density. Even though the number of women with BB type is small, we noted the mean serum level of each bone marker was greater in postmenopausal women with BB type than in premenopausal women with the same genotype.In conclusion, this may suggest a partial agreement of our data with that of Australlian group and that we have to try to find out another genotype specifically related with lower bone density in Korean women.

Complication and Prognosis of Craniopharyngioma According to the Age of Onset.: Eun Jig Lee, Moon Suk Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Kun Hoon Song, Bong Soo Cha, Ji Hyun Lee; J Korean Endocr Soc. 1994;10(3):262-272. Published online November 6, 2019

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Abstract PDF: Craniopharyngioma is the most common tumor involving the hypothalamo-pituitary area in childhood and adolescence. Recently, we carried out collective review of 70 patients with craniopharyngioma treated from January 1980 to December 1994 in order to inverstigate the endocrine outcome and survival according to the age of onset.The following results were obtained:1) The male to female ratio was 1:1. Age at diagnosis ranged from 2 to 64 years(mean age: 23) with the greatest frequency in the 2nd decade of life(28.6%). Of the 70 cases, the first group, 27 cases were under the age of 15, and the other group, 43 cases were over 15 year-old.2) The most common symptom at diagnosis in both groups was headache. In the adult group, symptoms related to hypogonadism(amenorrhea, decreased libido, galactorrhea etc.) were not uncommon. The lag of time between onset of symptom and hospital visit ranged from 3 days to 156 months(mean: 20 months).3) The main site of tumor was suprasellar region in both groups. The most common CT finding in both groups was calcification in sella turcica.4) In pre-operative combined pituitary function test, the most common, abnormal responses were shown in growth hormone and thyroid stimulating hormone in both groups. In addition, prolactin frequently showed abnormal response in the adult group.In post-operative combined pituitary function test, more hormones tended to reveal abnormal response in the group treated with surgery plus radiation therapy.5) The operation by subtotal removal followed by radiation therapy was the most commonly used method in treatment of both groups. After treatment, panhypopituitarism was occurred more frequently in the group treated with RT after surgery than those treated with surgery alone, but the difference was not statistically significant(p=0.136 in childhood, 0.436 in adults). Except the cases with panhypopituitarism, the most commonly encountered endocrine abnormalities were growth retardation in the children group, and hypogonadism in adult. The recurrence was clinically observed in 11 cases. The recurrence rate were 11.1% in children, and 18.6% in adult respectively. The mean time from the initial treatment to recurrence was 23 months. There was no significant difference in recurrence rate between the group treated with RT after subtotal removal and the group treated with total removal(p=0.475).The overall five-year survival rate after treatment was 82.8%. According to the treatment modalities, the patients undergone RT after subtotal removal survived much longer than those treated with other modalities such as subtotal removal only or total removal, but the differences in survival were not statistically significant(Log rank test, p=0.0539).

Case Reports

A Case of Nesidioblastosis in Adult with Hyperinsulinemic Hypoglycemia.: Young Kee Shong, Hong Kyu Kim, Young Joo Min, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Duck Jong Han, Ho Jeong Lee, Ghi Su Kim, Gyung Yub Gong; J Korean Endocr Soc. 1994;10(3):273-277. Published online November 6, 2019

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Abstract PDF: Nesidioblastosis is a primarily childhood disease which is often associated with hyperinsulinemic hypoglycemia. It is very rarely found in adults. Only a few well documented cases are found in the world interature. The authors have recently experienced a case of nesidioblastosis in an adult. A 55-year-old man was admitted due to repeated episodes of reversible loss of consciousness. Hyperinsulinemic hypoglycemia was documented. Under the presumptive diagnosis of insulinoma, localization procedures were done but no definite tumor was found. Only suspicious gradient in insulin concentration was found around the head of pancreas by percutaneous transhepatic portal venous sampling. Exploratory laparotomy was performed and Whipple's operation was done. Seventy percent of proximal pancreas was removed. Histomorphometric study of the resected specimen revealed uneven graded hyperplasia of the islet cells with the most profuse hyperplasia in the head region and progressive decrease in the degree of hyperplasia to the body and tail. The patient remains euglycemia until 6 months after operation since immediate postoperative period and can tolerate 24 hour fasting without any medication.

A Case of Idiopathic Juvenile Osteoporosis.: Moon Suk Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Young Joon Weon, Bong Soo Cha, Ji Hyun Lee, Jung Ho Lee; J Korean Endocr Soc. 1994;10(3):278-283. Published online November 6, 2019

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Abstract PDF: Idiopathic juvenile osteoporosis is a rare disease of heterogenous etiology and occurs on children between the age of 8 and 15. Manifestations include bone pain, fractures in minimal trauma, reduced bone density at areas of new bone growth, and loss of height. It is important to exclude other causes of osteoporosis.We experienced a case of a 14 year old boy with idiopathic juvenile osteoporosis. He had suffered from pain in the back and difficulty on walking for two months. Radiologic finding of the thoracolumbar area of the spine showed generalized severe osteoporosis and multiple vertebral collapse. We could not find the causes of osteoporosis in biochemical study, bone marrow study, skin biopsy and hormonal study. He was treated with alphacalcidol and CaCO_3. After 4 month of initial management, his subjective symtoms were improved and we did not find any signs of progression of disease. On bone mineral density measured after 26 month, we observed markedly increased bone mineral density.We report our experience of follow up of this case and review with the disease reported in the literature.

A Case of Giant Cell Granuloma of The Pituitary Gland.: Eun Jig Lee, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Tae Seung Kim, Sun Ho Kim, Bong Soo Cha, Dong Hun Choi, Jeong Il Jeong; J Korean Endocr Soc. 1994;10(3):284-288. Published online November 6, 2019

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Abstract PDF: Granulomatous disease of the pituitary gland are uncommon disorders which are rarely diagnosed in patients presenting for hypophysectomy. The majority of reported cases come from neuropsy material and include infectious and systemic disease such as tuberculosis, sarcoidosis, syphilis and fungal infections. We experienced giant cell granuloma of the pituitary gland in a 47 years-old woman. The patient suffered from headache, polyuria and polydipsia. MR images of brain demonstrated a hyposignaled mass. The fibrous tissues were removed by transsphenoidal approach. The clinical and histopathological features of this rare entity are reviewed.

A Case of Propylthiouracil - Induced Hepatitis; Showed Chronic Active Hepatitis by Pathologic Finding.: Yoon Sok Chung, Hyeon Man Kim, Deok Bae Park, Kwang Hwa Park, Chull Sim, Min Kyung Song, Heui Chul Chung; J Korean Endocr Soc. 1994;10(3):289-294. Published online November 6, 2019

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Abstract PDF: A 15-year old girl developed propylthiouracil-induced hepatitis documented as chronic active hepatitis by liver biopsy, who had suffered from Graves' disease for 1 year and treated with propylthiouracil. The result of lymphocyte transformation test was negative which was performed after 3 months of onset of hepatitis.

A Case of Pheochromocytoma Diagnosed as Preeclampsia during Prenancy.: Bong Yun Cha, Ho Young Son, Soon Jip Yoo, Ki Hyun Baik, Myung Hoon Kim, Moo Il Kang, E Jin Choi, Kwang Woo Lee, Sung Koo Kang, Uk Kim, Jong Man Won, Jin Young Yoo; J Korean Endocr Soc. 1994;10(3):295-299. Published online November 6, 2019

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Abstract PDF: A case of a pregnant woman with an undiagnosed pheochromocytoma is presented. Gestational hypertension was developed at 33 weeks' gestation. Also she experienced intermittent chest discomfort, headache and irritability during those period. Normal vaginal delivery was successfully performed with close observation. Even though experiencing same symptoms for two years after delivery, she had been treated as neurosis. Uncatched pheochromocytoma was detected and the tumor was resected successfully. It seems to be that many cases of pheochromocytoma with pregnancy still go unrecognized because of close similarity between pheochromocytoma and toxemia. High index of suspicion should be maintained to achieve early diagnosis because antenatal diagnosis can lower the mortality in both mother and fetus.

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