Endocrinology and Metabolism

Volume 19(5); October 2004

Original Articles

Polymeric Gene Carriers and Their Applications to Diabetes Gene Therapy.: Min Hyung Lee; J Korean Endocr Soc. 2004;19(5):463-472. Published online October 1, 2004

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Abstract PDF: No abstract available.

Relationship between Adiponectin, Leptin and Body Fat in Men with Hypogonadism Before and After Testosterone Treatment.: Sang Wan Kim, Joon Ku Kang, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2004;19(5):473-484. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Testosterone replacement therapy in men with hypogonadism improves sexual function, decreases body fat, and increases the mass and function of lean muscle. These beneficial effects of testosterone replacement therapy are accompanied by slight lowering of the high density lipoprotein (HDL) cholesterol levels, increase in the hematocrit/hemoglobin ratio and size of the prostate gland. It is presently unknown whether the effect of testosterone on body fat could also reduce the risk of atherosclerotic disease associated with obesity. We investigated the relationship between body fat and blood leptin and adiponectin levels to elucidate the effect of testosterone on body fat metabolism, as well as the effect of testosterone on lipid and bone metabolism. METHODS: We selected 28 men, who were hypogonadal (mean serum testosterone+/-SD, 22.3+/-35.3 ng/dL) due to an organic disease, and them with oral testosterone (testosterone undecanoate) for 12 months. We measured the body composition, serum leptin, plasma adiponectin, biochemical bone markers, bone mineral density, prostate-specific antigen, and serum lipids before and 3, 6 and 12 months after treatment. We analyzed the relationship between body fat and blood leptin and adiponectin levels. RESULTS: The mean serum testosterone concentration reached the subnormal range after 6 months of treatment, which remained for the duration of treatment. The fat mass decreased and muscle mass increased, not within the first 6 months, but principally within 12 months (p<0.05). Although the decrease in the serum leptin level was not statistically significant, there were positive correlations between the leptin level and fat mass before and after 6 months of treatment (p<0.05). The plasma adiponectin did not increase or correlate with body fat parameters. The bone mineral densities of the lumbar spine (L2-L4) and femoral neck did not increased, but the serum osteocalcin and urine N-telopeptide were significantly decreased (p<0.05 and <0.01, respectively). The HDL-cholesterol decreased, principally within the first 6 months (p<0.01), but the total and LDL cholesterols, and the triglycerides remained unchanged during the course of treatment. There was also no change in prostate-specific antigen. CONCLUSION: Twelve months of oral testosterone replacement in men with hypogonadism improved body composition and bone metabolism, but demonstrated subnormal serum testosterone levels, had no effect on the leptin and adiponectin levels and decrease in HDL-cholesterol levels. It will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as cardiovascular risk factors in men with hypogonadism

Effects of Pamidronate Treatment on Osteogenesis Imperfecta.: Seung Won Lee, Hyon J Kim, Jae Hyun Cho, Hyoung Suk Lee, Youn Mu Jung, Dae Jung Kim, Kwan Woo Lee, Yoon Sok Chung; J Korean Endocr Soc. 2004;19(5):485-491. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Osteogenesis imperfecta (OI) is a congenital disorder of type I collagen, with variable phenotypes, due to increased bone fragility and low bone mass. Previous pharmacological treatments for OI have been attempted with calcitonin and growth hormone but with little beneficial effects. Recently, Glorieux reported the beneficial effects of bisphosphonates in OI. METHODS: In this study, the effects of pamidronate treatment were evaluated in 9 patients with OI. All patients received intravenous pamidronate infusions, which was dose adjusted according to the patients' age. The outcome measures included the biochemical bone markers; serum alkaline phosphatase, urine deoxy-pyridinoline, urine Ca/Cr ratio, and bone mineral density (BMD). RESULTS: Serum alkaline phosphatase, urine deoxypyridinoline, and urine Ca/Cr ratio were slightly decreased after 1 year of therapy, although these changes were not statistically significant. The BMDs of the lumbar spine and proximal femur were significantly increased after 1-year of pamidronate treatment. No fractures were reported during the 1 year treatment periods. CONCLUSION: Pamidronate treatment had an effect on the BMD in osteogenesis imperfecta, probably due to decreasing bone resorption

Relationship between Serum Adiponectin and Development of the Metabolic Syndrome.: S S Park, K M Choi, S B Kwon, O H Ryu, H J Ryu, S Y Park, H Y Kim, J A Seo, K W Lee, S G Kim, N H Kim, D S Choi, S H Baik; J Korean Endocr Soc. 2004;19(5):492-500. Published online October 1, 2004

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Abstract PDF: BACKGROUND
We investigated whether low serum adiponectin concentrations are able to predict the future development of type 2 diabetes and metabolic syndrome. METHODS: This was a prospective cohort study, which included 372 elderly Koreans that participated in the South-West Seoul (SWS) study, conducted in 1999 and 2002 in Seoul, Korea. Fasting and post-challenge 2-hour plasma glucose, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid profiles, and serum adiponectin data were examined. RESULTS: Adiponectin concentrations obtained in 1999 and 2002 were highly correlated (r = 0.63, P < 0.0001), and the three-year within-person variation of the adiponectin concentrations was not significant (P=0.61). The serum adiponectin level was closely correlated with metabolic syndrome; negatively with BMI, WHR, blood pressure, triglyceride and blood glucose, and positively with HDL cholesterol. Subjects with metabolic syndrome showed lower serum adiponectin concentrations than those without (P < 0.0001). The baseline adiponectin levels were found to be correlated with subsequent changes in the WHR, LDL cholesterol, and fasting and post-load 2h glucose over the 3-year period, after adjusting the baseline values. A multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, gender, obesity, history of impaired fasting glucose or impaired glucose tolerance, hypertension and dyslipidemia. CONCLUSION: Reduced concentrations of adiponectin were found to be independently associated with increase risks of both type 2 diabetes and metabolic syndrome in elderly Koreans

The Abundance and Nuclear Distribution of TonEBP in Response to Changes of Tonicity in Hyperglycemic Cells .: Won Kun Park; J Korean Endocr Soc. 2004;19(5):501-510. Published online October 1, 2004

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Abstract PDF: BACKGROUND
TonEBP (Tonicity-responsive enhancer binding protein) regulates the transcription of tonicity responsive genes, such as sodium-myo-inositol and the sodium- chloride-betaine co- transporters (SMIT & BGT1), heat shock protein 70 (HSP70) and aldose reductase (AR). To characterize the signals that activate TonEBP in hyperglycemic human retinal pigment epithelial (hRPE) cells, the abundance and nuclear distribution of TonEBP were studied in response to changes of tonicity in culture media. METHODS: After the cultures reached confluence, the hRPE cells were exposed for 3 days to 25 mM glucose and 100 mM NaCl, both with and without 20 M tolrestat. The expressions of AR, SMIT and HSP 70 were determined by northern blot, and the abundances of TonEBP by western blot. The nuclear distributions of TonEBP were observed by fluorescence microscopy, after immuno staining. RESULTS: The AR and SMIT mRNA levels in hyperglycemic and hypertonic media were decreased compared to those in hypertonic media alone. These decreased AR and SMIT mRNA expressions were also observed to be significantly prevented in those cells incubated with tolrestat. Stimulation of TonEBP in hypertonic medium occurs due to a combination of an increased abundance of TonEBP and an increased distribution into the nucleus from the cytoplasm. However, the expressions and nuclear distributions of TonEBP in hyperglycemic and hypertonic media were not different from those in hypertonic media alone. CONCLUSION: The expressions of AR and SMIT genes that may influence the development of diabetic complication were down-regulated by the intracellular accumulation of sorbitol in sustained hyperglycemia. TonEBP does not play a key role in the hypertonicity-induced transcriptional regulation of AR and SMIT in hyperglycemic cells, due to the intracellular accumulation of sorbitol and depletion of myo-inositol

Role of Pexoxisome Proliferator Activated Receptor Gamma in Growth Regulation of Thyroid Cancer Cells.: Tae Yong Kim, Ja Young Song, Young Kee Shong, Won Bae Kim; J Korean Endocr Soc. 2004;19(5):511-521. Published online October 1, 2004

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Abstract PDF: BACKGROUND
There is currently no effective option for the treatment of poorly differentiated thyroid carcinomas, so further studies are needed to evaluate new therapeutics. Thiazolinedione, an agonist of peroxisome proliferator activated receptor gamma (PPAR ), is known to suppress the growth of various tumor cell lines. This study was conducted to see if PPAR is involved in growth regulation of poorly differentiated thyroid cancer cells. SUBJECT AND METHODS: Thyroid cancer cell lines with a low degree differentiation, such as ARO and FRO cells were used, and their expression of PPAR mRNA checked. The effects of known agonists (rosiglitazone and 15-deoxy-delta12,14-prostglandin (15d-PGJ2)) and antagonists for PPAR (bisphenol A diglycidyl ether (BADGE)) on the growth of thyroid cancer cell lines expressing PPAR were evaluated by various methods, such as the methylthiazoletetrazolium bromide (MTT) assay, cell counts, and [3H]thymidine uptake. RESULTS: The expressions of PPAR were higher in ARO and FRO cells than in those of normal thyroid. Form the results of the MTT assay, the survival of ARO and FRO cells were found to decrease after administration of rosiglitazone or 15d-PGJ2. However, no change was observed after administration of BADGE. When the effect of rosiglitazone was evaluated by cell counting, there was significant decrease in number of ARO and FRO cells, but no change was observed after administration of 15d-PGJ2. Similar results were obtained using [3H]thymidine uptake. Thus, rosiglitazone treatment significantly decreased the [3H]thymidine uptake, whereas 15d-PGJ2 showed no significant effect. CONCLUSION: PPAR agonists (rosiglitazone and 15dPG-J2) suppressed the survival of ARO and FRO cells, undifferentiated thyroid cancer cell lines, with increased expressions of PPAR . However, the cell count and [3H] thymidine uptake were affected by rosiglitazone, but not by 15dPG-J2. This might suggest the antiproliferative effects of rosiglitazone are independent of PPAR ; and therefore, mediated by another unknown mechanism

Case Reports

A Case of Apical Hypertrohic Cardiomyopathy Associated with Pheochromocytoma.: Joon Ho Moon, Sung Woo Park, Sung Hee Ihm, Cheol Young Park, Ki Won Oh, Cheol Soo Choi, Seong Jin Lee, In Kyung Jung, Eun Gyung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Moon Gi Choi, Hyung Joon Yoo, So Young Ku, Soo Kee Min; J Korean Endocr Soc. 2004;19(5):522-527. Published online October 1, 2004

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Abstract PDF: Pheochromocytomas often present with cardiovascular manifestations, such as arrhythmia, angina pectoris and acute myocardial infarction and so on. Both dilated and nonobstructive hypertrophic cardiomyopathies are also rare complications of pheochromocytomas. In hypertrophic cardiomyopathy, an apical variant form constitutes about 25% of cases in Japan, but only 1 to 2% of those in non-Japanese populations, including Korea. The cause of apical hypertrophic cardiomyopathy (AHC) remains unknown. Recently, some cases of AHC associated with pheochromocytomas have been reported, with catecholamine thought to be an important cause. AHC associated with a pheochromocytoma has never been previously reported in Korea. Herein is reported our experience of a case of apical hypertrophic cardiomyopathy associated a pheochromocytoma with a review of the literature

A Case of Cerebral Infarction in Young Woman with Graves' Disease and Atrial Fibrillation.: Young Yong An, Yi Sun Jang, Hyung Doo Kim, Ji Young Park, Hong Gun Bin, Hye Soo Kim, Jong Min Lee, Suk Young Kim, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; J Korean Endocr Soc. 2004;19(5):528-534. Published online October 1, 2004

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Abstract PDF: Thyrotoxicosis associated atrial fibrillation occurs in 9 to 22% of hyperthyroidism patients; its prevalence increases after the age 60 years. Atrial fibrillation is known to be major independent risk factor for a thromboembolic stroke. The characterization of patient subgroups with atrial fibrillation, with high or low rate risk factor of a stroke, would help clinicians decide the benefit or harm to patient of long term anticoagulation therapy. Thyrotoxicosis, old age, hypertension, diabetes, heart failure, history of stroke and thromboembolism are all high risk factors for a stroke in atrial fibrillation patients. Thus, anticoagulation therapy is recommended for stroke prevention in those groups with atrial fibrillation and thyrotoxicosis. Herein is reported a case of acute cerebral infarction, with thyrotoxic atrial fibrillation and congestive heart failure, in a young woman

A Case of Silent Corticotroph-cell Adenoma with Elevated Serum ACTH.: Jeong Geun Moon, So Young Park, Byoung Chul Cho, Jung Min Lee, Si Hoon Lee, Yoo Mee Kim, Yu Mie Rhee, Bong Soo Cha, Hyun Chul Lee, Sung Kil Lim; J Korean Endocr Soc. 2004;19(5):535-541. Published online October 1, 2004

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Abstract PDF: A 48 year-old man was referred to our Department with a headache, and also presented with an elevated serum ACTH level, but without an elevated serum cortisol. Although there was no clinical evidence of Cushing's syndrome, a brain CT and MRI showed a 4x4.5 cm sized pituitary mass, which was successfully removed by a transsphenoidal approach (TSA). A histopathological examination revealed the mass to have an ACTH positive reaction. Therefore, through hormonal and pathological evaluation, a silent corticotroph-cell adenoma (SCCA), with an elevated serum ACTH level, was diagnosed. Although reports on SCCA have been recently increased, this case is reported because these kinds of tumor are still rare, and those SCCA with an elevated serum ACTH even more so

A Case of Adrenal Insufficiency Associated with Antiphopholipid Syndrome with SLE.: Sun Hye Shin, Jung Hee Kim, Jung Min Son, Jeong Su Kim, Min Ah Na, Yang Ho Kang, Ok Nyu Kong, Seok Dong Yoo, Seok Man Son, In Ju Kim, Yong Ki Kim; J Korean Endocr Soc. 2004;19(5):542-545. Published online October 1, 2004

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Abstract PDF: Systemic lupus erythematosus (SLE) is autoimmune disease that often develops antiphopholipid syndrome (APS). Lupus anticoagulant and anticardiolipin antibodies are the hallmarks of APS. The hypercoagulable state in APS may lead to adrenal vein thrombosis, and subsquently lead to hemorrhagic necrosis of the adrenal gland. Adrenal hemorrhage is a very rare complication of APS. Although there have been some reports about adrenal hemorrhage associated with primary APS, adrenal hemorrhage associated secondary APS in SLE has not yet been reported. We describe the adrenal hemorrhage associated with secondary APS in SLE, and the patient which complained of general weakeness, nausea, vomiting and diffuse abdominal pain. Abdominal magnetic resonance imaging (MRI) showed hemorrhage, of both renal glands, and clinical features and immunological studies were consistent with APS in SLE. The acute adrenal insufficiency was much improved after the patient was treated with glucocorticoids

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