Endocrinology and Metabolism

Volume 17(1); February 2002

Original Articles

Molecular Insights into Fat Cell Differentiation and Functional Roles of Adipocytokines.: Jiyoung Park, Jae Bum Kim; J Korean Endocr Soc. 2002;17(1):1-9. Published online February 1, 2002

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Abstract PDF: No abstract available.

TSH Receptor Antibodies: Recent Update and Clinical Applications.: Won Bae Kim, Young Kee Shong; J Korean Endocr Soc. 2002;17(1):10-19. Published online February 1, 2002

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The Effects of Glucocorticoids on Osteoblast.: Yong Ki Min; J Korean Endocr Soc. 2002;17(1):20-22. Published online February 1, 2002

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Effects of Glucocorticoid on Apoptosis of Human Bone Marrow Osteogenic Stromal Cells.: Ha Young Kim, Duk Jae Kim, Si Yeol Lee, Jeong Soo Hong, Dong Kwan Kim, Ghi Su Kim; J Korean Endocr Soc. 2002;17(1):23-31. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Osteoporosis is one of the most serious side effects of long-term glucocorticoid therapy, but the mechanism of glucocorticoid-induced bone loss remains poorly defined. Glucocorticoid induces decreased bone formation and death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess may affect the birth or death rate of bone cells and thereby reduce their numbers. It has been known that reduction in bone formation is due to reduced proliferation in osteoblast precursor cells and reduced matrix synthesis in mature osteoblast. Here, we present evidence for dexamethasone-induced apoptosis on human bone marrow stromal cells (hBMSC). To understand the mechanism of glucocorticoid-induced osteoporosis, we investigated the effects of glucocorticoid on primary cultured hBMSC. METHEODS: Treatment with dexamethasone at the concentration of 10-9 M for 3~5 days significantly decreased cleavage tetrazolium salt WST-1 level/concentration by mitochondrial dehydrogenase in viable cells. Greater decrease was observed with higher concentration of dexamethasone (10-7 M, and 10-5 M). Apoptosis was measured by annexin V binding/propidium iodide using fluorescence-activated cell sorter (FACS) analysis and nuclear morphology stained with the fluorescence dye, Hoechst 33342. RESULTS: The level/concentration of apoptotic hBMSC (annexin V positive / PI negative) was increased with 10-9 M dexamethasone (1.2% to 5.3%) and further increased with 10-7 M, and 10-5 M concentration (11.7% and 12.5%, respectively). The same result was observed with Hoechst 33342 staining. CONCLUSION: These results indicate that glucocorticoid induces apoptosis on osteoblast precursor cell, hBMSC, and may contribute to decrease bone formation

Comparison of Treatment Modalities in Hyperprolactinemia.: Sun Hee Park, Hyeon Jeong Jeon, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2002;17(1):32-42. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Prolactinomas have been treated primarily with bromocriptine, a dopamine agonists, rather than by transsphenoidal pituitary adenomectomy. However, lower success rates, as well as intolerance or resistance to medical therapy, have been reported in some recent series. The purpose of this study was to compare the effects of surgery and bromocriptine in the treatment of prolactinomas patients. Also we investigated the natural history and effects of bromocriptine on patients with idiopathic hyperprolactinemia. METHEODS: We retrospectively compared the effects of treatment with surgery and with bromocriptine in 27 idiopathic hyperprolactinemia patients, 35 microprolactinoma patients and 61 macroprolactinoma patients. RESULTS: (1) In 14 patients with untreated idiopathic hyperprolactinemia, 8 (57%) achieved remission. In patients without remission, preoperative serum prolactin level was significantly higher than patients with remission (p<0.05). In 13 patients on bromocriptine, 11 (85%) achieved remission, while the other 2, taking bromocriptine irregularly because of side effects, had persistent hyperprolactinemia. (2) In 35 patients with microprolactinoma, 11 (30%) surgery as initial therapy and surgical remission was achieved in only 5 of the 11 (45%). In 23 patients on bromocriptine, 17 (74%) achieved remission. Among the 6 patients without remission, 5 patients took bromocriptine irregularly because of side effect. (3) In 61 patients with macroprolactinoma, 49 (80%) underwent surgery as initial therapy and surgical remission was achieved in only 9 of the 49 (18%). In 50 patients on bromocriptine, 30 (60%) achieved remission. Among the 20 patients without remission, 13 took bromocriptine irregularly because of side effect and 5 were resistant to bromocriptine. CONCLUSION: In idiopathic hyperprolactinemia, the requirement for medical treatment is doubtful because of a high tendency to ward spontaneous cure. In spite of the low success rate, surgery has been used as the primary therapy for prolactinoma in Korea. And yet, medical treatment with bromocriptine is superior to surgery. However, irrgular administration of medication due to drug side effects was the main cause of the low success rate. Therefore, the necessity for new drug development is emphasized

Korean Adult Growth Hormone Deficiency Treatment Registry.: Sung Woon Kim, Seong Yeon Kim, Su Youn Nam, Yoon Sok Chung, Jae Hoon Chung, In Kyung Jung, Jong Ryeal Hahm, Minho Shong, Dong Sun Kim, Seong Keun Lee, Sung Dae Moon, Hyun Koo Yoon, Doo Man Kim, Sang Woo Kim, Hye Kyung Park; J Korean Endocr Soc. 2002;17(1):43-47. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Adult growth hormone (GH) deficiency is related with decreased lean body mass, increased body fat, and poor quality of life. In western countries, adult GH deficiency treatment registriesy provide a database of the effects and safety of GH deficiency treatment. The Korean Adult Growth Hormone Study Group of the Korean Society of Endocrinology register adult GH deficiency since 1996. METHEODS: Subjects were aged over 15 years, had organic hypothalamo-pituitary disease, and GH deficiency as documented by GH stimulation test or serum insulin-like growth factor-I (IGF-I) level. The underlying etiology for GH deficiency, serum IGF-I level, starting and maintenance dose, and adult GH deficiency assessment (AGHDA) score were investigated. RESULTS: From January 1996 to May 2001. 115 patients were enrolled. Mean age was 43.7 13.8 years and 60% were female. Thirteen medical institutions were involved in the registry. The most common underlying diseases were Sheehan's syndrome and pituitary adenomas. GH starting dose was from 0.4 to 1.0 units. Maintenance dose was between 0.5 and 1.2 units. Serum IGF-I levels were increased after GH treatment (0-week, 93.7 69.7 ng/mL; 2-weeks, 184.9 89.0 ng/mL; 6-weeks, 188.4 94.8 ng/mL; 10-weeks, 207.6 111.1 ng/mL; 6 months, 281.9 95.5 ng/mL). AGHDA scores slightly improved from 10.25 6.70 to 8.58 5.47 after 6 months of GH deficiency treatment. CONCLUSION: The GH Treatment Registry will be beneficial in monitoring the effects of GH deficiency treatment on Korean adult GH deficient subjects

Effect of Class 2 Transactivator on Expression of Thyroid Transcription Factor-1 in FRTL-5 Cells.: Won Bae Kim, Tae Yong Kim, Young Joo Park, Jae Joon Koh, Do Joon Park, Bo Youn Cho; J Korean Endocr Soc. 2002;17(1):48-56. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Gamma-interferon (gamma-IFN) is known to suppress thyroperoxidase (TPO), thyroglobulin (Tg), thyrotropin receptor (TSHR) mRNA expression via unclarified mechanism. Thyroid transcription factor-1 (TTF-1) is a nuclear protein involved in the maximal expression and tissue specific expression of thyroid-specific antigens (TPO, Tg, TSHR, NIS) in thyrocytes. Although It's plausible that gamam-IFN induced suppression of thyroid-specific antigen expression may be mediated by decrease of TTF-1 expression, such an effect has not been documented yet. In this study we investigated the effect of gamma-IFN on the expression of TTF-1 in the rat thyroid cell, FRTL-5, and determined whether such an effect is mediated by sclass 2 transactivator (CIITA). METHEODS: The mRNA expression of TTF-1 was quantitated by northern blot analysis after treatment of gamma-IFN, and after expression of CIITA in FRTL-5 cells. Four different promoter constructs were made by cloning into the pRSV-luciferase vector, each contained 5'flanking sequence of different lengths (-5.18 kb, -4.11 kb, -1.94 kb, -1.15 kb) of rat TTF-1 gene. Effects of gamma-IFN and CIITA on promoter activities were analyzed by luciferase assay in FRTL-5 cells into which each promoter construct had been transfected by DEAE-dextran method. RESULTS: Steady state TTF-1 mRNA level at 48 h after gamma-IFN treatment (100 U/mL) was significantly decreased from that of the pre-treatment level (1.65+/-0.16 vs. unit, p<0.05). In all 4 promoter constructs gamma-IFN significantly suppressed promoter activities compared to the vector only transfected cells. CIITA expression in FRTL-5 cells significantly decreased the steady state TTF-1 mRNA level when compared to that in mock-transfected cells (1.69+/-0.31 vs. 1.17+/-0.44 arbitrary unit, p<0.05). CIITA expression in FRTL-5 cells caused suppression of promoter activities in -5.18 kb and -4.11 kb constructs, but had no effects on those activities in -1.94 kb; and -1.15 kb constructs. CONCLUSION: gamma-IFN, directly and indirectly via CIITA expression, suppressed the transcription of TTF-1 gene in the FRTL-5 cells. It may be one of the mechanisms involved in the gamma-IFN-induced suppression of thyroid-specific protein expressions in thyrocytes 1.25+/-0.27 arbitrary

Percutaneous Ethanol Injection in Autonomous Functioning Thyroid Nodules and Complex Cysts: Five Years' Experience.: Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn; J Korean Endocr Soc. 2002;17(1):57-68. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection therapy (PEI) performed with ultrasonography guidance has recently been used in cases of autonomous functioning thyroid nodules (AFTN) and benign complex cysts. We performed this study to analyze the effects of PEI on AFTN and benign complex cysts. METHEODS: From September 1995 to September 2000, we performed PEI on 456 outpatients (47 men and 409 women, mean age 42.4+/-11.8 years) with AFTN or benign complex cysts. All cases were subjected to fine needle aspirations (FNA) by ultrasonography-guidance if necessary. FNA was performed at least twice with results of colloid nodule in cases of complex cysts. For AFTN, cases with FNA results of follicular neoplasm were also included. After PEI on AFTN, patients were classified into three response groups: complete response as judged by our new criteria (CR, normalization of TSH and free T4, disappearance of hot nodule on thyroid scan) along with the old criteria of previous studies (normalization of TSH and free T4, recovery of suppressed extranodular tissue on thyroid scan), partial response (PR, normalized free T4 but suppressed TSH, persistent hot nodule despite recovery in suppressed extranodular tissue) and no response (no change of hot nodule). Complex cysts were classified into three groups in accordance with volume reduction after PEI: complete response (CR, above 90% of volume reduction), partial response (PR, 50~89%) and no response (below 50%). RESULTS: Overall pre-treatment volumes were 15.3+/-12.1 mL and post-treatment volumes were 2.8+/-2.9 mL, with 66.4+/-19.9% of volume reductions in AFTN and complex cysts. Volume reductions were 71.5+/-18.0% in AFTN, and 66.1+/-15.0% in complex cysts. In 24 cases of AFTN, responses satisfying the previous criteria were 14 (58.3%) of CR, 6 (25.0%) of PR, and 4 (16.7%) of no response. However, by the new criteria there were 1 (4.2%) of CR, 10 (41.6%) of PR, and 13 (54.2%) of no response. In 432 cases of complex cysts, CR was observed in 82 (19.0%), PR in 261 (60.4%) and no response in 89 (20.6%). The volume reductions in complex cysts with pre-treatment volume larger than 15 mL were higher than those of groups with smaller volumes (p<0.001). Pre-treatment volumes were not correlated with post-treatment volumes, nor with volume reductions. Volume reductions were not correlated with the amounts of injected ethanol. Mild and transient complications were observed in 41 cases (9.0%) during PEI, consisting of transient neck pain (n=36, 7.9%), transient unilateral vocal cord palsy (n=3, 0.7%), intracavitary hemorrhage (n=1, 0.2%), and transient hypotension (n=1, 0.2%). CONCLUSION: Our data suggest that the efficacy of PEI on AFTN is temporary and does not usually induce long-term complete remissions. In complex cysts, however, PEI may have potential as an additive treatment modality to thyroid hormone suppressive therapy

The Effects of Iodide on the Cellular Functions and Expression of Thyroid Autoantigens in Thyroid Cells.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Hye Seung Jung, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2002;17(1):69-78. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro

Serum Leptin Levels in Relation to Quantitative Ultrasound Values of Calcaneus in Korean Postmenopausal Women in Chung-Up District.: Sang Wook Kim, Jung Min Koh, Ha Young Kim, Duk Jae Kim, Ghi Su Kim; J Korean Endocr Soc. 2002;17(1):79-86. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Obese postmenopausal women usually have a tend to have greater bone mineral density than lean women. This has been attributed to either the mechanical effects of their excessive weight on bone tissue or to their high body fat content. A recent study demonstrated that leptin, the hormone produced in adipocytes, acts on bone metabolism. These findings have prompted speculations on the possible role of leptin in the protective effect of obesity on bone. METHEODS: We studied the relationship between serum leptin levels and quantitative ultrasound (QUS) values of calcaneus in 94 postmenopausal Korean women who were randomly selected from the population of the Chung-Up osteoporosis prevalence study. QUS values, broadband ultrasound attenuation and speed of sound; were measured at the calcaneus. RESULTS: Leptin values were strongly correlated with body mass index (r = 0.478, p< 0.001), confirming a positive relationship between leptin levels and fat mass. In contrast, no significant correlations were observed between serum leptin levels and calcaneal QUS values. CONCLUSION: Our results suggest that circulating plasma leptin does not have a significant influence on QUS values of calcaneus in Korean postmenopausal women.

Relationship between Plasma Leptin Levels and Carotid Intima-Medial Thickness in Korean Adults.: Hyejin Lee, Eunsoon Hong, Youngsun Hong, Yeon Ah Sung; J Korean Endocr Soc. 2002;17(1):87-94. Published online February 1, 2002

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Many studies have recently shown that leptin can promote angiogenesis via endothelial leptin receptors and induce oxidative stress in endothelial cells; These findings suggest the relationship between cardiovascular risk and blood leptin concentration. In the present study, we investigated the relationship between leptin concentration and carotid intima-medial thickness (CIMT) as an indicator of early atherosclerosis in adults. METHEODS: The study subjects comprised 138 (45 men and 93 women; mean age 42.4+/-7.5 years; mean BMI 24.0+/-2.7 kg/m2) without history of diabetes, hypertension or cardiovascular disease. We measured CIMT by high resolution ultrasonography and plasma leptin levels by radioimmunoassay. RESULTS: 1) No significant differences in age, BMI or CIMT between male and female subjects were noted, but the leptin levels in female were significantly higher than those in males. (8.42+/-5.90 ng/mL vs. 3.08+/-1.00 ng/mL, p<0.001) 2) CIMT showed a significant positive correlation with age (r=0.31, p< 0.001), BMI (r=0.25, p<0.01) and level (r=0.42, p<0.05) in simple regression analysis. 3) When male and female subjects were each divided into 3 groups by leptin concentration, no significant difference in CIMT among female subjects was found. In male subjects, CIMT was significantly higher in the highest tertile of leptin level than in the other 2 groups (0.65+/-0.03 mm vs. 0.56+/-0.07 mm and 0.53+/-0.07 mm, p<0.01) after adjustment for BMI and age. However, this difference was not significant after adjustment for smoking. 4) CIMT (0.61+/-0.05 mm vs. 0.53+/-0.07 mm, p<0.01) and leptin concentrations (3.57+/-2.13 ng/mL vs. 2.20+/-1.39 ng/mL, p<0.05) were significantly higher in male smokers than in male non-smokers. CONCLUSION: Our results demonstrated significant correlation of CIMT to plasma leptin level before adjustment for smoking. A possible explanation is the permissive action of smoking on the atherogenic effect of leptin. However, further studies to elucidate the relationships and interactions among smoking, leptin level and the development of atherosclerosis will be needed.

Hypertensive Complications in Patients with Primary Aldosteronism.: Seong Hee Kwon, Yeong Min Cho, Heoung Kyu Park, Do Jun Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Yeon Cho, Hong Kyu Lee; J Korean Endocr Soc. 2002;17(1):95-103. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Primary aldosteronism (PA) is believed to be a benign form of secondary hypertension due to the low incidence of hypertensive complications. Recently, several studies have shown that hypertensive complications were common in patients with PA. Therefore, we investigated hypertensive complications in 46 PA patients. METHEODS: Clinical and laboratory features of 46 46 patients were retrospectively analyzed. Hypertensive complications of this group were left ventricular hypertrophy, cerebrovascular accidents, hypertensive nephropathy and hypertensive retinopathy. RESULTS: Hypertensive complications were found in 30 (65.2%) of the 46 patients. The incidence of severe hypertension (higher than or equal to 110 mmHg in diastolic blood pressure) was 17.6%. Left ventricular hypertrophy was found in 26 (56.7%) of the 46 patients. Cerebrovascular accidents were found in 6 patients, and hypertensive nephropathy in 4 patients. The incidence of severe hypertensive retinopathy (higher than or equal to grade 3 in the Keith-Wagener Barker classification) was 17.6%. Of the 35 PA patients who underwent surgical treatment hypertension was found in 18 (51.4%). CONCLUSION: These results indicate that hypertensive complications are common in patients with PA, suggesting that early detection, treatment and close follow-up are necessary in PA.

Case Reports

A Case of Panhypopituitarism Due to Craniopharyngioma with Slipped Capitalis Femoral Epiphysis.: Jun Hee Lee, Kyung Rae Kim, Hi Yan Park, Jin Yang Ju, Young Duk Chae, Soo Jee Yoon, Ki Joong Kim, Woo Il Park, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 2002;17(1):104-109. Published online February 1, 2002

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Abstract PDF: Craniopharyngioma accounts for 3% to 5% of intracranial tumors and is the second most common neoplasm in the sellar region. Panhypopituitarism associated with craniopharyngioma has been reported in 7% of all patients with craniopharyngioma. Slipped capital femoral epiphysis is the condition in which the femoral head slips downward and backward on the femoral neck at the epiphyseal plate due to growth disturbance of capital physis, the actual cause of which is unknown. It is a disease of adolescence, during which many physiologic hormonal changes occur. The clinical association between slipped capital femoral epiphysis and endocrine disease is well known. There have been four cases of slipped capital femoral epiphysis associated with endocrine disorders in Korea. This is the first Korean case report of slipped capital femoral epiphysis combined with craniopharyngioma caused by hypopituitarism

A Case of Acromegaly with Diabetic Ketoacidosis and Hypertriglyceridemia-Induced Acute Pancreatitis .: Choon Young Lee, Moon Kyu Lee, Sun Young Lee, Sung No Hong, Hyung Hoon Kim, Bo Hyun Kang, Han Wook Kang, Byung Wan Lee, Yu Jeong Park, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Jong Hyun Kim; J Korean Endocr Soc. 2002;17(1):110-116. Published online February 1, 2002

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Abstract PDF: Secondary diabetes mellitus caused by increased growth hormone secretion (GH) has well been known. There is a close association between glucose intolerance and GH secretion, and increased GH level itself probably worsens the blood glucose control and lipid profile by increasing glycogenolysis and / or gluconeogenesis and by suppressing lipase activity. We report a case of acromegaly with diabetic ketoacidosis as and hypertriglyceridemia-induced acute pancreatitis. A 38 year old male, previously diagnosed to have acromegaly and diabetes, presented with nausea, vomiting, diffuse abdominal pain and altered mentality. There was no history of drug or alcohol consumption, blood gas analysis showed severe acidosis and urinanalysis for ketone was positive. His serum blood glucose, amylase and lipase levels were 494 mg/dL, 331 U/L, and 1288 U/L, respectively (reference values: 70~110 mg/dL, 13~100 U/L and 13~190 U/L, respectively). The patient was diagnosed as having diabetic ketoacidosis and acute pancreatitis. With the serum concentration of triglyceride being 1488 mg/dL and the absence of any obvious precipitating factors, we considered hypertriglyceridemia to be the cause of acute pancreatitis. He was treated with continuous intravenous insulin infusion, lipid lowering agent, and fluid replacement. After conservative management, general condition gradually improved and his serum amylase, lipase and triglyceride levels were all normalized. GH level was not suppressed under 2 ng/mL during oral glucose loading test, and basal GH and IGF levels were 231 ng/mL and 29.5 ng/mL, respectively. Sella MRI showed a 3.7 cm sized pituitary mass. On the 55th day of admission, transsphenoidal surgery was performed. In immunohistochemical staining, the pathologic tumor specimen was proved to be GH positive pituitary adenoma. This is the first case reported in the English literature of an acromegaly presenting with diabetic ketoacidosis and acute pancreatitis

Histomorphometry of Osteogenesis Imperfecta I.: Seong Bin Hong, Suk Myun Ko, Yong Koo Park, Young Joo Park, Yoon Juo Oh, Young Wan Kim, Sung Ki Kim, Moon Suk Nam, Yong Seong Kim; J Korean Endocr Soc. 2002;17(1):117-123. Published online February 1, 2002

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Abstract PDF: Osteoporosis imperfecta (OI) is a genetic disorder characterized by fragility of bone, deafness, blue sclerae; and laxity of joints. Four types of OI are distinguished by clinical findings. Although mutations affecting collagen I are responsible for the disease in the most patients, the mechanism by which the genetic defects cause abnormal bone development has not been well established. Therefore we evaluated static and dynamic bone histomorphometry of type I OI in the case study of a 15 year old boy with OI who had blue sclerae, a history of frequent fracture and a familial history of blue sclerae. Biopsy of the ilium showed loss of connection between the cortical bone and trabecular bones. The Harversian system in the cortical bone was poorly developed. In the trabecular bones, the lamellar pattern was poorly developed. Mineral apposition rate of the cortical bone was 1.0 m/day and of the trabecular bone was 0.79 m/day. Thus OI might be regard as a disease whereby abnormal collagen synthesis interferes with bone strength by multiple mechanisms.

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