Endocrinology and Metabolism

Volume 17(5); October 2002

Review Article

Medical Therapy of Somato Statin Analog in Acromegaly.: Kyoung Wook Lee, Moon Suk Nam; J Korean Endocr Soc. 2002;17(5):629-634. Published online October 1, 2002

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Abstract PDF: No abstract available.

Editorial

Graves' Disease and Immunoglobulin E.: Huun Kyung Chung; J Korean Endocr Soc. 2002;17(5):635-639. Published online October 1, 2002

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Abstract PDF: No abstract available.

Original Articles

The Relationship between Graves' Disease and Serum Immunoglobulin-E.: Hyun Young Kim, Ki Ryong Park, Seoung Hoon Kim, Jee Yeon Kim, Soo Keun Song, Young Sik Choi, Yo Han Park; J Korean Endocr Soc. 2002;17(5):640-648. Published online October 1, 2002

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Abstract PDF: BACKGROUND
It is widely believed that Graves' disease is an autoimmune disorder characterized by the presence of the circulating TSH receptor antibody (TRAb). The majority of the activity of TRAb is of the immunoglobulin G (IgG) class. However, other immunoglobulin such as immunoglobulin E (IgE), may play a role in the activity. IgE accumulation has been reported to occur in the thyroid gland and ocular muscles of subjects with Graves' disease. Furthermore, it has been noted that recurrence of Graves' disease can be induced by an allergy to pollen. Because an allergy to pollen is commonly associated with IgE, IgE might play a role in the induction of Graves' disease. Therefore, investigated whether IgE was elevated in Graves' disease, and evaluated the potential relationship between the levels of TRAb and IgE Graves' disease. METHODS: Forty-six patients with Graves' disease, and 6 with chronic thyroiditis, diagnosed at the Kosin Medical Center between April, 2000 and July, 2000 were included in this study. Thirty-five persons without thyroid disease or a history of allergic rhinitis were used as normal controls. The level of TRAb was measured using thyrotropin binding inhibitory immunoglobulin (TBII). Serum total IgE was measured using an enzymeimmunoassay method. Test for thyroid function, TBII and total IgE were performed in all cases, and the results statistically analyzed. RESULTS: TBII, as IgG, and the serum IgE level were higher in the patients with Graves' disease, and the levels of the latter were 598.1+/-1112.9U/mL, 98.5+/-79.7U/mL and controls 161.7+/-194.4U/mL in the Graves' patients, those with thyroiditis and the controls, respectively (p<0.05). The prevalence of allergic rhinitis in Graves' disease was 10.9%. The serum IgE level in Graves' disease with, and without, allergic rhinitis were 903.1+/-1152.2U/mL and 560.8+/-1117.0U/mL, respectively, although there was no significancant difference between the two groups. According to the clinical stage, the serum TBII level was higher in the untreated Graves', and relapsed patients 49.9+/-23.9% and 21.1+/-3.1%, respectively, than in the treated group, 7.4+/-18.6% (p<0.05). The serum IgE level was higher in the untreated Graves' and relapsed patients 758.6+/-1250.2U/mL and 1198.5+/-1952.1U/mL, respectively, than in the treated group 233.8+/-432.7U/mL, although this was not significant. According to the duration of treatment, the serum TBII levels were higher in the untreated Graves' patients, and those treated for less than 1 year, than in those treated for more than 1 year, with values of 49.9+/-23.9, 24.8+/-3.8 and 2.22+/-1.97%, respectively (p<0.05). The serum IgE level was higher in the untreated Graves' disease (758.6+/-1250.2U/mL) than in the groups treated for less than 12 months (158.3+/-91.5U/mL) and more than 12 months (252.7+/-483.4U/mL), but the differences were not significant. CONCLUSIONS: The concentration of IgE was high in Graves' patients, and although not statistically significant, the serum IgE level in Graves' patients with allergic rhinitis was higher than those without. With regard to the clinical stage of Graves' disease, the change in the IgE level tended to follow that of the TBII. Further study will be required to define the possible role of IgE in the pathogenesis in Graves' disease.

Clinical and Ultrasonographic Characteristics of Malignant Thyroid Incidentalomas.: Hahn Wook Kang, Kwang Won Kim, Byung Wan Lee, Bo Hyun Kang, Hyung Hoon Kim, Bum Jin Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee; J Korean Endocr Soc. 2002;17(5):649-656. Published online October 1, 2002

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Abstract PDF: BACKGROUND
High-resolution ultrasonography has made the detection of asymptomatic small thyroid possible. Recent increases in the detection of incidentalomas have created a clinical dilemma on how to properly manage such incidental nodules. We investigated the prevalence, clinical and ultrasonographic characteristics, and optimal diagnostic approach toward incidentally detected benign and malignant thyroid nodules of less than 1.5 cm in size. METHODS: A retrospective review was undertaken on the 1,475 patients who had visited Samsung Medical Center, Seoul Korea between January 1999 and December 2000. The review consisted of a physical examination of the thyroid gland, thyroid function test, antithyroid antibodies, thyroid ultrasonography, fine-needle aspiration biopsy, pathology and TNM staging of the incidentally detected thyroid nodules of less than 1.5 cm in size. RESULTS: The prevalence of thyroid incidentalomas was 13.4% and the malignancy rate within them was 28.8%. There were no significant differences in age, sex, thyroid function test and size between the benign and malignant incidentalomas. Ultrasonographic characteristics showed meaningful diagnostic value for the detection of malignancy in incidentalomas. Most malignant incidentalomas were of a low stage. CONCLUSION: Occult thyroid cancers are fairly common finding. There are no clinical difference between benign and malignant thyroid nodules less than 1.5 cm ; however, ultrasonographic fingings can be used to decision of optimal management strategies.

Completion Thyroidectomy in Patient with Differentiated Thyroid Cancer Who Initially Underwent Ipsilateral Operation.: Eun Sook Kim, Jung Min Koh, Won Bae Kim, Suck Joon Hong, Young Kee Shong; J Korean Endocr Soc. 2002;17(5):657-663. Published online October 1, 2002

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Abstract PDF: BACKGROUND
In some instances, thyroid cancer may be diagnosed only after resection of a putative or suspected benign nodule. In these cases a complete thyroidectomy is usually recommended to prevent recurrence. We analyzed the frequency of malignancy in the contralateral lobe after a complete thyroidectomy, and assessed the factors that may predict the presence of a malignancy, which might necessitate a complete thyroidectomy. METHODS: Between 1995 and 2001, 65 patients, who initially underwent a lobectomy and isthmectomy, but were finally diagnosed with differentiated thyroid carcinoma, underwent complete thyroidectomies. Their mean age was 39.8 +/- 12.4 years, ranging, 14 to 71 years. After initial surgery, 45 proved to have follicular carcinomas, 18 papillary carcinomas, 1 medullary and 1 insular carcinoma. The mean tumor size was 4.0 +/- 1.8 cm, ranging from 0.3 to 8.5 cm. After a complete thyroidectomy, the presence of a tumor the at contralateral lobe was assessed according to clinical parameters and the pathological findings in the ipsilateral lobe. RESULTS: The first surgeries revealed tumor multifocality in 27 cases, perithyroidal tumor extension in 4 and lymph node metastasis in 1. On completion of the thyroidectomy, 22 of the 65 patients had a malignancy in the contralateral lobe. Age, sex, size or the pathological primary tumor type, were not associated with the presence of additional tumors at the contralateral lobe. Tumor multifocality at the first surgery was the only significant variable to predict the presence of a tumor in the contralateral lobe. CONCLUSION: When thyroid cancer is diagnosed after ipsilateral surgery, the only predictive factor for the presence of a contralateral tumor was multifocality. We believe that a complete thyroidectomy is mandatory in these cases.

The Changes of Serum Growth Factors after Hematopoietic Stem Cell Transplantation: Impact on Bone Mineral Metabolism.: Ki Hyun Baek, Eun Sook Oh, Ki Won Oh, Won Young Lee, Hye Soo Kim, Soon Yong Kwon, Je Ho Han, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim; J Korean Endocr Soc. 2002;17(5):664-674. Published online October 1, 2002

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Abstract PDF: BACKGROUND
A loss of bone mass is usually detected after a bone marrow transplantation (BMT), especially during the early post-transplant period. We recently reported that enhanced bone resorption following a BMT was related to both the steroid dose and the increase in IL-6. We also suggested damage to the marrow stromal microenvironment, by myoablation, partly explains the impaired bone formation following a BMT. It is well known that some growth factors play important role in bone growth and osteogenesis. However, the pathogenetic role of bone growth factors in post-BMT bone loss is unknown and data on the changes in the growth factors, in accordance with bone turnover markers and bone mineral density (BMD) changes are scarce. We investigated changes in bone growth factors such as IGF-I (Insulin-like growth factor-I), fibroblast growth factor-2 (FGF-2) and Macrophage colony stimulating factor (M-CSF), during the post-BMT period, and assessed whether the growth factor changes influenced the bone turnover and post-BMT bone loss. The present study is the first prospective study to describe the changes in bone growth factors following a BMT. METHODS: We prospectively investigated 110 patients undergoing a BMT, and analyzed 36 patients (32.4+/-1.3 years, 17 men and 19 women) whose BMDs were measured before, and 1 year after, the BMT. The serum biochemical markers of bone turnover were measured before, 1, 2, 3 and 4 weeks, 3 and 6 months, and 1 year, after the BMT. The serum FGF-2, IGF-I and M-CSF levels were measured before and 1 and 3 weeks, and 3 months after the BMT. The correlation between the changes of growth factors and various bone parameters was analyzed. RESULTS: The mean bone losses in the lumbar spine and total proximal femur, calculated as the percentage change from the baseline to the level at 1 year, were 5.2 (p<0.05) and 11.6% (p<0.01), respectively. The serum type I carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 6 months after the BMT, but thereafter decreased, to the base value after 1 year. Serum osteocalcin, a bone formation marker, decreased progressively, until 3 weeks after the BMT but then increased transiently, and finally returned to the base level at 1 year. The serum IGF-I and FGF-2 also decreased progressively until 3 weeks and 1 week after the BMT, respectively, then increased to the base values at 3 months. The serum M-CSF increased briskly at 1 week post-BMT, then decreased to the base level. There were positive correlations between the percentage changes from the baseline proximal femur BMD and the IGF-I levels 3 weeks and 3 months (r=0.52, p<0.01, r=0.41, p<0.05) post BMT. A Significant correlation was found between the IGF-I and osteocalcin levels pre-BMT, and 3 weeks after the BMT. Another positive correlation was found between the M-CSF and the ICTP levels at 3 weeks post BMT (r=0.54, p<0.05). CONCLUSION: In conclusion, there were significant changes in the serum IGF-I, FGF-2 and M-CSF levels in the immediate post-BMT period, which were related to a decrease in bone formation and loss in the proximal femoral BMD during the year following the BMT

The Relationship between Dehydroepiandrosterone sulfate and Insulin Resistance Syndrome in Women.: Hyo Jeong Kim, Eun Soon Hong, Jee Young Oh, Young Sun Hong, Yeon Ah Sung; J Korean Endocr Soc. 2002;17(5):675-684. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Dehydroepiandrosterone (DHEA) is an androgen precursor, and is known to be decreased by the aging process. DHEA has been known to have a protective effect on insulin resistance and cardiovascular disease in men, but remains controversial in women. The aim of this study was to elucidate the role of DHEA on insulin resistance, and the risk for cardiovascular disease, in women. METHODS: We analyzed the relationship between DHEA sulfate (DHEAS), known to have a longer half-life and less diurnal variation than DHEA, and insulin resistance syndrome (IRS) in 471 non-diabetic women from an urban community diabetes prevalence study. Serum DHEAS concentrations were measured using a commercially available radioimmunoassay kit. RESULTS: 1. The frequencies of obesity, impaired glucose tolerance, hypertension and dyslipidemia were 25.3, 8.5, 21.9 and 6.2%, respectively, and the frequency of IRS was 16.5%. 2. DHEAS was significantly inversely correlated with age (r=-0.47, p<0.001), systolic blood pressure (r=-0.18, p<0.001), diastolic blood pressure (r=-0.10, p<0.05), fasting serum glucose (r=-0.10, p<0.05), postchallenge 2 hour glucose (r=-0.12, p<0.01) and triglycerides (r=-0.16, p<0.01). 3. As serum DHEAS concentrations, by quartiles, were decreased, the age-adjusted frequency of hypertension was significantly increased (p<0.05). 4. A Multiple linear regression analysis revealed that DHEAS was significantly associated with age (p<0.0001) and BMI (p<0.05). 5. A Logistic regression analysis showed that DHEAS was not associated with IRS after adjustment for age. CONCLUSION: DHEAS is inversely associated with age. DHEAS has no harmful effect, and may even have a protective role, on insulin resistance syndrome. Prospective examinations of DHEAS and insulin resistance syndrome in women are needed to confirm the mechanism for the association between DHEAS and the development of cardiovascular disease.

Impaired Metabolic Signal Transduction Networks in Isolated Skeletal Muscle in Korean type 2 Diabetic Patients.: Joon Hyuck Choi, Kwan Woo Lee, Hyo Jeong Kim, Dong Hun Lee, Jong Woo Lee, Jung Eun Kim, Hyun Chae Yim, Kyung Mi Kim, Sung Yi Choi, Yoon Sok Chung, Hyeon Man Kim; J Korean Endocr Soc. 2002;17(5):685-697. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-beta), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes (n=9) and control subjects (n=11). METHODS: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphorylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-beta), Akt and GSK-3. RESULT: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA1c in controls and diabetic patients were 98.+/-1.3 and 208.1+/-16.5 ng/dl, and 5.4+/-0.5 and 9.2+/-0.6%, and 1.4+/-0.2 in the control subjects, and 72.2+/-52.3% (p<0.01) and 10.2+/-6.3 (p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp tests were 8.2+/-0.6 mg/kg/min and 3.7+/-1.1 ng/kg/min in the control subjects and in the diabetic patients, respectively (p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively (p<0.05). CONCLUSION: In korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus

Case Reports

A Case of Cerebral Salt Wasting Syndrome associated with Tuberculous Meningitis.: Seung Hyuk Rho, Ji Yong Choi, Taek Man Nam, Hyeon Kyu Kim, Seong Jin Lee, In Kyung Jeong, Eun Gyung Hong, Cheol Soo Choi, Doo Man Kim, Jae Myung Yu, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park, Hyoung Cheol Kim; J Korean Endocr Soc. 2002;17(5):698-704. Published online October 1, 2002

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Abstract PDF: Hyponatremia in patients with central nervous system disorders is suggestive of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and volume restriction is recommended for its correction. However, if volume depletion is present in a situation otherwise compatible with SIADH, cerebral salt wasting syndrome (CSWS) should be considered as the cause of the hyponatremia to avoid hypovolemic shock that may be induced by the standard management of SIADH, i.e. volume restriction. We present a case of a 17-year-old male patient with CSWS associated with tuberculous meningitis. The clinical feature of the patient comprised hyponatremia, excessive natriuresis, polyuria, and hypovolemia. Following the administration of saline and fludrocortisone, natriuresis and polyuria were decreased, and the hyponatremia improved

Lymphocytic Hypophysitis associated with Pregnancy.: Seong Jin Lee, Hyang Lim Lee, In Kyung Chung, Eun Gyung Hong, Cheol Soo Choi, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; J Korean Endocr Soc. 2002;17(5):705-712. Published online October 1, 2002

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Abstract PDF: Lymphocytic hypophysitis is a rare inflammatory disease of the pituitary gland that is often recognized as a cause of hypopituitarism and may be due to the autoimmune pituitary destruction that usually occurs in women in the peripartum period. We report a rare case of lymphocytic hypophysitis in a 26 year-old woman presenting with nausea and headaches for 2 months after an artificial abortion of her second pregnancy. Magnetic resonance imaging, with enhancement, showed an expanding 1.0x1.0 cm sized sellar mass. The patient underwent transsphenoidal surgery with a preoperative diagnosis of pituitary macroadenoma. A histological examination revealed diffuse lymphocytes and plasma cells infiltration which are characteristic of lymphocytic hypophysitis. Here, we present the first reported case of a pregnant woman with lymphocytic hypophysitis with a review of the literature on this increasingly recognized condition.

A Case of Lymphocytic Hypophysitis in a Postmenopausal Woman.: Sang Hyun Baik, Dong Sun Kim, Yoon Kyoung Sung, Jong Pyo Kim, Chang Beom Lee, Yong Soo Park, Woong Hwan Choi, You Hern Ahn, Tae Wha Kim, Yong Ko, Moon Hyang Park; J Korean Endocr Soc. 2002;17(5):713-719. Published online October 1, 2002

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Abstract PDF: A 64-year-old Korean woman presented with a 3-week history of severe headache and ocular pain. Her brain MRI showed a cystic pituitary mass compressing the optic chiasm. A hormonal study revealed anterior pituitary insufficiency and a slightly increased prolactin level. We performed a transsphenoidal resection of the pituitary mass. A pathological examination revealed the presence of a heavy inflammatory infiltrate, composed of lymphocytes and plasma cells, and destruction of the adenohypophysial structures. Five months after surgery, her hormonal levels had nearly normalized, without hormone replacement therapy. A follow-up MRI showed no recurrence. We conclude that lymphocytic hypophysitis should be included in the differential diagnosis of pituitary mass at any age. We discuss the features that can help to make a preoperative differential diagnosis, and selection of the appropriate treatment.

Diffuse nesidioblastosis underwent reoperation after streptozotocin treatment.: Hyun Hoon Kim, In Kyung Jeong, Byung Wan Lee, Sang Yop Shin, Duck Shin Cho, Jong Wook Yun, Bum Jin Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Young Lyun O, Yeon Lim Suh, Mi Kyung Park, Kwang Won Kim; J Korean Endocr Soc. 2002;17(5):720-729. Published online October 1, 2002

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Abstract PDF: Nesidioblatosis is a term that describes small clusters of pancreatic islet cells budding off exocrine ducts, and is commonly reported in infants with intractable idiopathic hypoglucemia. The onset of nesidioblastosis in adults is an extremely rare entity associated with hypersecretion of insulin and the treatment of choice is pancreatic resection. Medical treatment, including somatostatin, propranolol, diazoxide, hydrochlorthiazide and streptozotocin have achieved limited success. We experienced a case of adult nesidioblastosis that underwent reoperation after the failure of medical treatment following an inappropriate first operation. A 54-year old man was admitted due to intermittent hypoglycemic symptoms, which had been relieved by carbohydrate ingestion. Hyperinsulinemic hypoglycemia was documented during a prolonged fast. Image studies found no localized lesion, so a distal pancreatectomy was performed. The pathological examination of the resected pancreas revealed irregularly sized islets and a scattering of small endocrine cell clusters throughout the acinar tissue and ductuloinsular complex. After a partial pancreatectomy the hypoglycemia had not disappeared. The patient did not want to undergo a reoperaton due to the post operative wound infection that occurred after the distal pancreatectomy. Therefore, diazoxide, somatostatin, propranolol, and streptozotocin was used as the alternative to an operation. However, the hypoglycemia persisted during and after the medical treatment. Finally, he underwent a near total pancreatectomy (85%), and the hypoglycemia disappeared. The extent of pancreatectomy is important in clinical outcome of patients with nesidioblastosis

A Case of Papillary Thyroid Carcinoma Combined with Multiple Endocrine Neoplasia Type 2A.: Ja kyung Kim, Hae Won Chung, Hye Sun Seo, Dae Jung Kim, Sang Su Chung, Young Duk Song, Kuk Hwan Kwon, Yoon Mi Jin, Mi Kyung Lee, Sung Kil Lim, Il Jin Kim, Hio Chung Kang, Jae Hyun Park, Jae Gahb Park; J Korean Endocr Soc. 2002;17(5):730-738. Published online October 1, 2002

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Abstract PDF: Multiple endocrine neoplasia (MEN) type 2A is a syndrome of medullary thyroid carcinomas, pheochromocytomas and parathyroid hyperplasia. The simultaneous occurrence of medullary, and papillary, thyroid carcinomas is rare because they are derived from, apparently, different germ layers, the former from the neuroectoderm and the latter from the endoderm. We report a case of a papillary thyroid carcinoma, combined with a medullary thyroid carcinoma, in a patient with MEN type 2A. Molecular genetic studies for screening a RET proto-oncogene mutation revealed a point mutation in codon 631 on chromosome 10, which is reported as highly uncommon in MEN type 2A.

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