Effects of the Serum Adiponectin to Tumor Necrosis Factor-alpha (TNF-alpha) Ratio on Carotid Intima-Media Thickness in Newly Diagnosed Type 2 Diabetic Patients

OBJECTIVES: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor - alpha (TNF-alpha), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-alpha ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-alpha levels on the progression of carotid atherosclerosis. METHODS: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-alpha were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-alpha levels (ADPN/TNF-alpha), baseline CIMT, and progression of CIMT at 1 year. RESULTS: ADPN/TNF-alpha negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011+/-0.138 mm). There was a negative correlation between ADPN/TNF-alpha and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. CONCLUSION: ADPN/TNF-alpha was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

Impact of Serum Adiponectin Concentration on Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Increased cardiovascular events, which is the leading cause of death in type 2 diabetic patients, are mainly caused by accelerated atherosclerosis. Adiponectin has been suggested as a risk factor for cardiovascular diseases in cross-sectional studies. However, little is known about the impact of adiponectin on the progression of carotid atherosclerosis in type 2 diabetic patients. This study was conducted to evaluate the impact of early adiponectin levels on the progression of carotid atherosclerosis. METHODS: From March 2009, 150 patients with type 2 diabetes were consecutively enrolled in our affiliated outpatient clinic. Anthropometric and biochemical data, including adiponectin levels, were measured in each participant. We measured the carotid intima-media thickness (CIMT) at baseline and at 1-year follow-up (n = 111). Then, we prospectively studied the relationship between the serum adiponectin levels and the progression of CIMT for 1 year. RESULTS: Adiponectin levels negatively correlated with CIMT (r = -0.219, P = 0.015). Moreover, mean progression of CIMT was 0.016 +/- 0.040 mm. However, there was no correlation between adiponectin levels and the progression of CIMT within 1-year follow-up period (r = -0.156, P = 0.080). Age (beta = 0.556, P = 0.004), LDL cholesterol (beta = 0.276, P = 0.042), and A1C (beta = 0.309, P = 0.038) were found to be independent risk factors for CIMT. However, A1C (beta = 0.311, P = 0.042) was found to be the only independent risk factor for the progression of CIMT. CONCLUSION: In our study, adiponectin levels were negatively associated with CIMT. However, it did not affect the progression of CIMT at 1-year follow-up. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients? / 당뇨병

BACKGROUND: Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated. RESULTS: With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093). CONCLUSION: Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

Duration of Preparation for Postoperative Radioiodine Administration in Differentiated Thyroid Carcinoma / 대한내분비학회지

BACKGROUND: Radioiodine treatment is effective for the removal of remnant thyroid tissues after thyroidectomy in patients with differentiated thyroid carcinoma. To induce the elevation of serum TSH level which facilitates the uptake of radioiodine into remnants, a 4 to 6 week interval between thyroidectomy and radioiodine administration has been established. During the period of preparation, most patients have experienced overt symptoms of hypothyroidism which have led to the development of alternative strategies. Some reports have suggested that the interval could be reduced to about 3 weeks with less symptoms. We reevaluated the adequate time needed for the elevation of serum TSH level above 30microU/mL after thyroidectomy. METHODS: Forty five patients who had undergone total thyroidectomy for differentiated thyroid carcinoma were investigated. Serum TSH and free T4 levels were measured one or more times within 3 weeks after operation(total 97 blood samples). Eighty nine blood samples were obtained within 15 days. RESULTS: In 41 patients (91.1%) serum TSH levels increased to 30 microU/mL until 15 days after operation. Until postoperative 21 days, serum TSH levels in all the other patients reached 30microU/mL. In linear equation, the daily increment of serum TSH levels was 2.62microU/mL for the first 8 days after operation and 5.34micorU/mL for the next 7 days. The half-life of serum free T4 levels showed marked individual variations. CONCLUSION: Measurement of serum TSH level at about 15 days after total thyroidectomy for differentiated thyroid carcinoma may be useful in determining the time of radioiodine administration.

A Case of Hashimoto's Thyroiditis with Transient T3-Thyrotoxicosis Induced by Hydatidiform Mole / 대한내분비학회지

Human chorionic gonadotropin(HCG) is a member of the glycoproteins family synthesized by the placenta, which consists of 2 noncovalently joined subunits(alpha(alpha) and beta(beta)). The alpha- and beta-subunits have a structural homology with the alpha- and beta-subunits of TSH and LH. The thyrotropic action of HCG results from its structural similarity to TSH, so beta-HCG can bind to the TSH receptor in the thyroid gland. A high level of HCG accompanied by an increased thyroid hormone level, can be observed in gestational trophoblastic disease (GTD), such as a hydatidiform mole or a choriocarcinoma, but the clinical symptoms of hyperthyroidism are rarely observed. We experienced a case of Hashimoto's thyroiditis, where the patient was diagnosed with T3-thyrotoxicosis, which had initially been induced by excess beta-HCG due to an H-mole; after evacuation of the H-mole, the condition was diagnosed as hypothyroidism. It has been speculated that a patient with Hashimoto's thyroiditis could have hyperthyroidism, induced by beta-HCG, due to an H-mole

A Case of Apical Hypertrohic Cardiomyopathy Associated with Pheochromocytoma / 대한내분비학회지

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 Adrenocortical Oncocytoma / 대한내분비학회지

Oncocytomas are neoplasms, histologically are composed of epithelial cells, with abundant, acidophilic and granular cytoplasm. Electron microscopic studies of oncocytomas have shown that the cytoplasm of oncocytes is packed with mitochondria. The adrenal gland is a very rare anatomical site for oncocytomas, and to the best of our knowledge, only thirty-six cases of adrenal oncocytomas have been described. Herein, a case of a large adrenal mass in a forty-year-old man, which was incidentally detected by abdominal ultrasonography, is presented. This patient demonstrated no clinical manifestation associated with adrenal hyperfunction. Hormonal studies showed no abnormal findings, except for a mild elevation of the 24-hour urinary VMA level. Abdominal computed tomography with enhancement revealed a large, well-defined left adrenal mass, measuring 5.0x.2 x.0cm. The patient underwent a left adrenalectomy, and a light microscopic examination confirmed an adrenocortical oncocytoma, with characteristic oncocytes and polygonal, abundant, eosinophilic and granular cytoplasm. The tumor cells were positive for cytokeratin and vimentin as well as S-100, but negative for chromogranin on immunohistochemical staining. An electron microscopic examination demonstrated closely packed mitochondria, containing intramitochondrial inclusions. After surgery, there was no evidence of a recurrent or distant metastatic disease at the 5 month follow-up. In summary, an extremely rare case of a man with an adrenocortical oncocytoma is reported, which was confirmed by histological examinations, including electron microscopy.

A Case of Masked Hypoglycemia during Lactic Acidosis / 대한내분비학회지

Severe hypoglycemia induces neuroglycopenic symptoms, including mental alteration, as glucose is the exclusive fuel for the central nervous system. However, some reports have shown that non-glucose fuels, like lactates and ketones, could be utilized by the brain during severe hypoglycemia. Herein, a case of extreme hypoglycemia in a 44-year old woman, subsequently diagnosed as congestive heart failure accompanied by ischemic hepatitis and lactic acidosis, is presented. In two episodes of extreme hypoglycemia, she was fully alert without obvious neurological deficits. In this unusual case, an increased supply of lactate might have maintained the cerebral function and prevented cerebral injury during the hypoglycemia that was induced as a result of starvation and hepatic and cardiac dysfunctions

A Case of Masked Hypoglycemia during Lactic Acidosis / 대한내분비학회지

Severe hypoglycemia induces neuroglycopenic symptoms, including mental alteration, as glucose is the exclusive fuel for the central nervous system. However, some reports have shown that non-glucose fuels, like lactates and ketones, could be utilized by the brain during severe hypoglycemia. Herein, a case of extreme hypoglycemia in a 44-year old woman, subsequently diagnosed as congestive heart failure accompanied by ischemic hepatitis and lactic acidosis, is presented. In two episodes of extreme hypoglycemia, she was fully alert without obvious neurological deficits. In this unusual case, an increased supply of lactate might have maintained the cerebral function and prevented cerebral injury during the hypoglycemia that was induced as a result of starvation and hepatic and cardiac dysfunctions

The Change of Pulmonary Artery Pressure in Graves'Disease Before and After Treatment / 대한내분비학회지

BACKGROUND: Exertional symptoms, dyspnea and impaired effort tolerance are common in patients with Graves' disease. Proposed explanations include: high-output left heart failure, ineffective oxygen utilization and respiratory muscle weakness. In addition, pulmonary hypertension has also been reported in patients with Graves' disease. A high prevalence of hypothyroidism and positive thyroid autoantibody were also observed in patients with pulmonary arterial hypertension. Therefore, the pulmonary artery pressure in patients with Graves' disease was evaluated. METHODS: Two-dimensional and Doppler echocardiographic examinations (Hewlett Packard Sonos 2500) were performed to determine the pulmonary artery (PA) pressure in 26 Graves' disease patients, both before and after treatment (23 patients with propylthiouracil and 3 with RAI), and in 10 euthyroid controls. The changes in the PA pressure after treatment were evaluated in 13 patients with Graves' disease, who became euthyroid after treatment. RESULTS: The pulmonary artery pressure was increased in the untreated Graves' disease patients compared to the normal controls (23.5+/-2.32 vs. 29.6+/-10.3 mmHg). 38.5% of the Graves' disease patients (10/26) showed pulmonary arterial hypertension (PA>30 mmHg) and the serum TBII levelwas higher in the Graves' disease patients with pulmonary arterial hypertension than in those with normal PA pressure (P<0.05). In the Graves' patients who became euthyroid after treatment, the PA pressure was significantly decreased. CONCLUSION: 38.5% of the untreated Graves' disease patients showed pulmonary arterial hypertension, and the pulmonary artery pressure was significantly decreased in those who became euthyroid after treatment. The pathogenesis and clinical importance of pulmonary arterial hypertension in Graves' disease requires further studies.

Thyroid Hormone Receptor Dynamics in Thyroid Hormone Response Elements of the Human Type 1 Iodothyronine Deiodinase Gene / 대한내분비학회지

BACKGROUND: Type 1 iodothyronine deiodinase (D1), the product of the hdio1 gene, is involved in thyroid hormone activation by the deiodination of thyroxine (T4) to form 3, 5, 3'-triiodothyronine (T3). Recent studies have identified two thyroid hormone response elements (TREs) in the 5 flanking region of the hdio1 gene. TRE1, proximal to TRE in the hdio1 gene, consists of a direct repeat of thyroid hormone receptor (TR) binding octamers with 10 bp separating the two TR binding sites. The upstream TRE, TRE2, is a classical direct repeat of retinoid X receptor (RXR)/TR binding half-sites with a 4-bp separation. There are few studies clarifying the TR dynamics in the TRE of a specific gene with or without the exposure of activated thyroid hormone. We evaluated TR binding patterns in the proximal and distal TREs of the hdio1 gene before and after T3 stimulation. METHODS: We employed chromatin immunoprecipitation (ChIP) technique to investigate the TR-TRE interaction before and after T3 stimulation in human hepatocellular carcinoma HepG2 cell line.Following cross-linking and sonication of the cells, immunoprecipitation was performed overnight at 4degrees C with TR 1, TR 1 and TR 2 antibodies. We analyzed the binding patterns and amounts of TR 1, TR 1 and TR 2 to TRE1 and TRE2 before and after 12 hours stimulation with 100 nM T3 by using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). Reverse transcriptional PCR (RT-PCR) and Western blot with TR 1, TR 1 and TR 2 antibodies were performed to measure the levels of hdio1 mRNA and TR 1, TR 1 and TR 2 proteins before and after 12 hours exposure to 100 nM T3. RESULTS: In TRE1, TR 1 binding was significantly decreased after 12 hours stimulation with 100nM T3 (3.74-->1.97, delta=-47.3%, p3.01, delta=-71.1%, p 2.93, delta=-76.7%, p 9.84, delta=+7.3%). Total TR bindings in TRE2 were significantly decreased after 12 hours stimulation with 100 nM T3 (32.14 --> 15.78, delta=-50.9%, p<0.05). The TR bindings to TRE1 and TRE2 were not significantly different by the amounts of TR antibodies used during ChIP assays. The levels of hdio1 mRNA were significantly increased, 2.03 times, after 12 hours exposure to 100nM T3 (p<0.001). Western blot showed no significant change of the level of each TR isoform protein before and after 12 hours exposure to 100 nM T3. CONCLUSION: Our results demonstrate the dynamics of TR 1 at proximal TRE (TRE1) and the switching phenomenon of TR isoforms at distal TRE (TRE2) of the hdio1 gene after T3 stimulation. Further investigation, however, is needed to clarify the mechanisms of these observations.

The Effect of T3 on Thyroid Hormone Receptor Dynamics in Thyroid Hormone Response Element of Chicken Lysozyme Silencer / 대한내분비학회지

BACKGROUND: The regulation of gene transcription can be controlled by both positive (enhancer) and negative (silencer) regulatory sequences. Several enhancer and silencer elements have been described in the 5' region of the chicken lysozyme gene. The silencer located at -2.4 kb upstream of the chicken lysozyme gene is composed of two separate modules (F1 and F2) that can function as silencers by themselves, but also show synergistic repression after multimerization. The F1 module is bound by a protein termed NeP1 and F2 module, a F2 thyroid hormone response element (F2-TRE), and can be bound by the thyroid hormone receptor (TR). F2-TRE has an inverted palindromic structure, with high affinity to TR. Although many current reported results have tried to explain the regulatory mechanism of chicken lysozyme gene expression due to the thyroid hormone, there have been few studies that clarify the TR dynamics in the F2-TRE of the chicken lysozyme gene, either with or without exposure of the thyroid hormone. Here, the changes in the TR binding patterns in the F2-TRE of the chicken lysozyme gene are described, both before and after T3 stimulation over time. METHODS: Using the stably transfected rat pituitary somatotroph tumor cell line, GC8 cells, with the F2-TRE inserted 5' to the thymidine kinase (TK) promoter, together with a mouse TRalpha- expressing plasmid, a chromatin immunoprecipitation (ChIP) technique was employed to reveal the TR-TRE interaction before and after T3 stimulation. Following the cross-linking and sonication of the cells, the immunoprecipitation was performed overnight, at 4 degrees C, with TRalpha1, TRbeta1 and TRbeta2 antibodies, respectively. The binding patterns and amounts of TRalpha1, TRbeta1 and TRbeta2 to the F2-TRE, before and after 12 hours of 100 nM T3 stimulation, were analyzed using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). The ChIP technique was used to give a basal value for 20 minutes and 1, 2, 4, 6, 8 and 12 hours after the 100 nM T3 stimulation, and RQ-PCR was then performed. Western blot with TRalpha1, TRbeta1 and TRbeta2 antibodies were also performed. RESULTS: After 12 hours of 100 nM T3 stimulation of the GC8 cells, the TRalpha1 and TRbeta2 binding to the F2-TRE increased, but the TR 1 binding to the F2-TRE decreased, by conventional PCR. Although all the TR isoforms were bound to the F2-TRE by RQ-PCR, the TR 1 binding to the F2-TRE, after 12 hours of 100 nM T3 stimulation, was significantly increased (1.01-->2.73, delta=+170.3%, p2.98, delta=+17.8%). The TRbeta1 binding was significantly decreased compared with that of the basal level (4.59-->2.06, delta=-55.1%, p7.77, delta=-4.4%). The binding patterns and amounts of TRalpha1, TRbeta1 and TRbeta2, both before and after the 100 nM T3 stimulation, were also identified over time. While the TRbeta1 bindings to the F2-TRE after 1 hour of 100 nM T3 stimulation were acutely reduced, those of the TRalpha1 at 20 minutes and 6 hours were increased. The TRbeta2 bindings showed a maximal increase at 20 minutes. The directions of the TR binding patterns, between the before and after 2 hours of 100 nM T3 stimulation, were identical to those for between 4 and 6 hours of T3 stimulation. There was no significant difference in the TR bindings to the F2-TRE in relation to the amounts (1.5 vs. 4.5 microliter) of TR antibodies used during the ChIP assays. The Western blots showed no significant change of the levels of each TR isoform proteins, either before or after 12 hours of exposure to 100 nM T3. CONCLUSION: These results show the dynamic binding patterns of the TR isoforms to the F2-TRE of the chicken lysozyme gene, both before and after T3 stimulation, over time. Further investigation, however, will be needed to clarify the mechanisms of our observations. The ChIP technique may then be used to reveal the dynamic models of the cofactors, as well as TR isoforms, in the TR-regulated transcription machinery.

A Case of Cerebral Salt Wasting Syndrome associated with Tuberculous Meningitis / 대한내분비학회지

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 / 대한내분비학회지

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.