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Volume 17(4); August 2002
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Review Articles
Hypothaqlamic Control of Food Intake and Bodyweight: Role of Melanocortins.
Ja Hyun Baik
J Korean Endocr Soc. 2002;17(4):433-444.   Published online August 1, 2002
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No abstract available.
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Thyroid Nodule.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2002;17(4):445-459.   Published online August 1, 2002
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No abstract available.
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Editorial
Non-alcoholic Fatty Liver Disease and Metabolic Syndrome.
Yong Seong Kim
J Korean Endocr Soc. 2002;17(4):460-464.   Published online August 1, 2002
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No abstract available.
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Original Articles
Effect of TRH on Phospholipase D Activity in GH3 Cell.
Dong Sun Kim, Chang Beom Lee, You Hern Ahn, Tae Wha Kim, Mee Sup Yoon, Joong Soo Han
J Korean Endocr Soc. 2002;17(4):465-472.   Published online August 1, 2002
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BACKGROUND
GH3 cells are a well characterized and widely used model used for the in vitro study of growth hormone (GH) secretion. Thyrotropin releasing hormone (TRH) binds to receptors belonging to the family of G protein-coupled receptors, and secrets both GH & prolactin. Phospholipase D (PLD) is an enzyme that hydrolyses phosphatidylcholine to yield phosphatidic acid and choline, and plays important roles in cellular proliferation and hormonal secretion. To elucidate the pathway of the action of TRH in GH3 cells, we investigated the activities of PLC and PLD in GH3 cells treated with TRH or phorbor 12-myristate 13-acetate (PMA). METHODS: GH3 cells were labeled with [3H] myristate, followed by incubation of with 0.3% ethanol, prior to before the addition of the agonists. The total lipids were extracted from the harvested cells following treatment with the agonists. The PLD activity was assessed by measuring [3H] phosphatidylethanol from the [3H] phospholipid using thin layer chromatography. RESULTS: TRH (1 muM) stimulated the PLC activity by 44-fold over that of the control values. TRH (1 microM), mastoparan (5 muM), and PMA (500 muM) for 30 minutes increased PLD activity by 1.9, 1.5 and 2.2 fold, respectively, in comparison to the controls. The PLD activities after 15, 30, 60, 120 and 240 min treatments of TRH (1 microM) were 142%, 170%, 172%, 160% and 115%, respectively. CONCLUSION: These results suggest that TRH stimulates not only the PLC activity, but also the PLD activity in GH3 cells.
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Changes in Hypothalamic-pituitary-growth Hormone (GH) Axis by Fasting: Study on the Differences between Male and Female Rats.
Sookjin Sohn, Mina Lee, Seungjoon Park
J Korean Endocr Soc. 2002;17(4):473-485.   Published online August 1, 2002
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BACKGROUND
Fasting has a profound impact on GH synthesis, and is released in all mammalian species that have been studied. The male rat has long been used as a model to determine the mechanism on how fasting mediates these changes. However, many aspects of GH synthesis, release and function are known to be gender-dependent. This study was conducted in order to determine if changes in the GH-axis, in response to fasting, differs between the sexes. METHODS: Male and female rats (8~9 weeks; n=5/group) were fasted for 72h, or supplied food ad libitum. The mean circulating serum GH and IGF-I concentrations were measured by radioimmunoassay. The levels of hypothalamic GH-releasing hormone (GHRH), somatostatin (SRIF), neuropeptide Y (NPY) and pituitary GH mRNA were measured using an RNase protection assay. The levels of pituitary GHRH receptor (GHRH-R), GH secretagogue (GHS) receptor (GHS-R) and SRIF receptor (sst1-5) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fasting resulted in a comparable weight loss in both the males and the females, (18.0+/-0.9%) and (17.0 0.8%), respectively. In the fasted males, there was a characteristic decrease in the serum GH (98 60 vs. 7 4 ng/mL) and IGF-I (367 35 vs 152 12 ng/mL), associated with a decrease in the hypothalamic GHRH, and an increase in the NPY mRNA, levels of 52 6% and 138 6%, respectively, compared to those of the fed controls (p<0.05). In spite of the reduction in the GHRH, fasting did not alter the levels of the pituitary GH mRNA, and in fact increased the expression of the pituitary receptors, GHRH-R and GHS-R, to 185 15 and 169 25%, respectively, to those of the fed controls. In contrast to the positive impact of fasting on the GH-stimulatory receptors, fasting led to a dramatic decrease in the expressions of the somatostatin receptor subtypes, sst2 (29+/-5% of Fed) and sst4 (60+/-7% of Fed). Fasting had comparable effects on the GH-axis of the female rats, with two notable exceptions; first, fasting did not suppress the mean circulating GH levels (16 3 vs. 38 28 ng/mL) and second, did not alter the sst2 and sst4 expressions. CONCLUSION: These results corroborate the other reports regarding the effects of fasting on the expressions of hypothalamic neuropeptides, pituitary GHRH-R and sst2, in male rats. This is the first report demonstrating that fasting stimulates the expression of pituitary GHS-R in both sexes. This is of great interest given the fact that ghrelin, the putative GHS-R ligand, is also elevated by fasting. We propose that the upregulation of both ghrelin and GHS-R may play important roles in increasing the sensitivity of the pituitary to GHRH, in that these GH-stimulatory systems work synergistically. These changes may compensate for the fasting-induced suppression of hypothalamic GHRH input. We might speculate that such compensatory mechanisms are dominant in the female rat, in that circulating GH levels are not suppressed by fasting.
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Fos Expression Induced by Combined Injection of Leptin and Cholecystokinin in the Rat Brain.
Young Uck Kim, Kyung Suk You, Ho Suck Kang, Choon Hee Chung, Tae Sun Hwang
J Korean Endocr Soc. 2002;17(4):486-500.   Published online August 1, 2002
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BACKGROUND
Several studies have reported that cholecystokinin (CCK), a short-term meal related satiety signal, and leptin, long-term signal for controlling feeding behaviour and body weight, act synergistically to inhibit food intake. However the mechanism and neuroanatomical basis for this response remain unclear. To clarify the neuronal mechanisms underlying the synergistic interaction between leptin and CCK, we examined the neuron activated by single or combined injection of leptin and CCK in fasted rats using immunohistochemistry for Fos. The expression of Fos can be used to trace neuronal activation pathways. METHODS: The rats were divided into 4 groups; Tris solution-saline, Tris solution-CCK, leptin-saline, leptin-CCK. Rats were received a single intracerebroventricular injection of either 3mul Tris solution or 3microgram leptin, and a single intraperitoneal injection of either 2mul saline or 2microgram/kg sulfated CCK-8. The changes of the Fos expression were investigated in the paraventricular nucleus (Pa), retrochiasmatic area (RCh), lateral hypothalamic nucleus (LH), central nucleus of amygdala(Ce), supraoptic nucleus (SO), arcuate nucleus (Arc), ventromedial hypothalamic nucleus(VMH),dorsomedial hypothalamic nucleus (DM), ventral premammillary nucleus (PMV), superior lateral subdivision of parabrachial nucleus (LPBS), external lateral subdivision of parabrachial nucleus (LPBE), supragenual nucleus (SGe), area postrema (AP), medial area (SolM) and commissural area (SolC) of nucleus of the solitary tract nuclei. RESULTS: CCK increased the Fos expression in the Pa, RCh, LH, Ce, SO, Arc, VMH, DM, PMV, LPBS, LPBE and SolM. Leptin increased the Fos expression in the Pa, RCh, LH, SO, Arc, VMH, DM, PMV, LPBS, LPBE, SGe, AP and SolM. Injections of leptin and CCK significantly enhanced the Fos expression in the Pa, RCh, VMH, DM, LPBS, and SolM compared with those induced by leptin or CCK alone. CONCLUSION: Our results suggest that the Pa, RCh, VMH, DM, LPBS and SolM may be essential sites mediating the synergistic effect of leptin and CCK to regulate food intake.
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Molecular Diagnosis of Recurrent Thyroid Cancer by Reverse Transcription-Polymerase Chain Reaction of Thyroglobulin Messenger Ribonucleic Acid in Peripheral Blood.
Sung Il Kwon, Ki Ryong Park, Hyun Young Kim, Chae Hee Shin, Young Chan Lim, Young Sik Choi, Yo Han Park, Kang Dae Lee, Hee Kyung Chang, Jae Hwa Lee, Ha Yong Yum
J Korean Endocr Soc. 2002;17(4):501-513.   Published online August 1, 2002
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BACKGROUND
Differentiated thyroid cancer is the most common endocrine malignancy. Despite advances in the treatment of thyroid cancer, disease recurrence and metastasis may occur in as many as 20% of patients, and so continues to pose major problems in its clinical management. Serum thyroglobulin (Tg) measurements, by immunoassay, are used to detect residual or recurrent thyroid cancer following thyroid ablation. However, the usefulness of immunoassay is limited by both the requirement for thyroid hormone withdrawal, to attain optimal test sensitivity, and interference by the antithyroglobulin antibody (Anti-Tg Ab). Recent studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of Tg mRNA in the peripheral blood of patients with differentiated thyroid carcinomas. We performed this study to evaluate the usefulness RT-PCR of Tg mRNA in peripheral blood of patients with thyroid carcinoma following a total thyroidectomy and radioiodine ablation therapy. METHODS: Forty cases that underwent a total thyroidectomy and radioiodine ablation therapy were included in this study. Of the 40 patients, 35 were papillary carcinomas and 5 were follicular carcinomas. Ten normal control subjects were also studied. Tg mRNA was extracted. Then RT-PCR, and nested RT-PCR, were run with specific Tg primers. Concurrently, DNA sequencing of the isolates was carried out to prove the isolates were identical to the nucleotide sequence of the Tg. RESULTS: The Tg was detected in 4 of 19 patients, with either a residual thyroid bed, or metastasis, on a 131I whole body scan and in 1 of 21 patients with a negative radioiodine scan. Surprisingly, the Tg mRNA was detected in all the patients and normal controls. CONCLUSION: From our results we can not recommend Tg mRNA, detected by RT-PCR in peripheral blood, as a tumor marker superior to that of the Tg serum level. We consider an intensive re-evaluation of the method is required before considering its clinical applications.
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Metabolic Abnormalities according to Severity of Non-alcoholic Fatty Liver Disease in Korean Adults.
H J Kim, D J Kim, S K Kim, S H Kim, Y M Rhee, C W Ahn, B S Cha, Y D Song, S K Lim, K R Kim, H C Lee, K B Huh
J Korean Endocr Soc. 2002;17(4):514-525.   Published online August 1, 2002
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BACKGROUND
We evaluated the frequency of non-alcoholic fatty liver diseases, and the associations between the metabolic abnormalities and severity of non-alcoholic fatty liver disease in Korean adults using ultrasonography. METHODS: We examined 1074 Korean adults above the age of 30 years, comprising of 502 men and 572 women, participating in medical check-ups at the Health Promotion Center. Hepatitis B and C serologies were negative, and the average weekly alcohol intake was < or = 2 standard drinks. A standard interview, physical exam and biochemical study, were conducted, and an experienced operator carried out ultrasound liver studies. RESULTS: 522 of the subjects had non-alcoholic fatty liver disease, and the remaining 552 did not. The frequency in the men was higher than that in the women (57 vs 42%, p<0.05). The frequency of non-alcoholic fatty liver disease in the subjects without diabetes, obesity or dyslipidemia was 20%. We classified subjects into 4 groups: the controls (n=552) and those with mild (n=218), moderate (n=273) or severe fatty liver disease (n=31), according to their ultrasonographic findings. BMI, waist circumference, body fat, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, the total- to HDL-cholesterol ratio, impaired fasting glucose, hypertension and insulin resistance, were all significantly increased with the increased severity of non-alcoholic fatty liver disease (p<0.05). Following the multiple regression analyses, waist, alanine aminotransferase, HOMAIR, the total- to HDL-cholesterol ratio, aspartate aminotransferase and systolic blood pressure, were all associated with the severity of non-alcoholic fatty liver disease. Odd ratios of insulin resistance in the mild, moderate and severe non-alcoholic fatty liver disease were 14.7 (CI: 6.8~32.0), 6.9 (CI: 4.6~10.3) and 5.7 (CI3.6~8.8), respectively. The percentages of subjects with insulin resistance in each group were 7.6, 32.0, 36.0 and 55.0% (p<0.05), respectively. The percentages of subjects with risk of non-alcoholic steatohepatitis in each groups were 5.0, 21.6, 27.8 and 58.1% (p<0.05) respectively. CONCLUSION: The frequency of non-alcoholic fatty liver disease was relatively high in Korean adults. Proportional differences in metabolic abnormalities, relation to the severity of non-alcoholic fatty liver disease, were found by ultrasonography.
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Association between Non-alcoholic Fatty Liver and Metabolic Diseases.
Hong Kyu Kim, Chan Jong Suh, Hyo Joong Yoon, Yong Ha Hwang, Kee Young Lee, Hye Young Park, Kap Hwan Kim, Moon Ho Kang
J Korean Endocr Soc. 2002;17(4):526-534.   Published online August 1, 2002
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BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is known to be frequently associated with obesity, type 2 diabetes and dyslipidemia. Recently, the diagnosis of fatty liver disease, based on ultrasonographic findings, has increased. Therefore, we examined the association between NAFLD and various metabolic diseases, such as obesity, glucose intolerance, dyslipidemia, and hypertension or metabolic syndrome, and tried to find out whether NAFLD was independently related to insulin resistance. METHODS: From April to June 2000, 262 subjects, attending for routine physical check-ups, were screened. Of these, 115 one hundred fifteen subjects were studied, with the other 147 excluded due to significant alcohol consumption, evidence of viral or toxic hepatitis, significant liver or renal dysfunction, and overt thyroid disease. Fatty liver was diagnosed if the subject had a "bright" liver on ultrasonographic examination. All diagnoses were made by a single experienced radiologist. RESULTS: Of the 115 subjects. 30 (26%) showed NAFLD. 1. Systolic and diastolic blood pressures, body weight, serum total cholesterol, triglyceride, fasting insulin levels and HOMA IR (homeostasis model assessment insulin resistance index) were higher in the subjects with NAFLD than in the controls. 2. Multiple logistic regression analysis, including age, sex, BMI, waist to hip ratio, fasting serum glucose, lipids and insulin levels, HOMA IR, and hypertension showed that BMI, total cholesterol and HOMA IR were independently related with NAFLD. 3. 27% of the subjects with NAFLD showed metabolic syndrome, and 53% of subjects with metabolic syndrome had NAFLD. 4. The percentage of subjects who had more than two factors of metabolic syndrome was three times higher in the subjects with NAFLD compared to the controls. CONCLUSION: These results suggest that NAFLD may be independently related with insulin resistance. Metabolic diseases, such as glucose intolerance, obesity, dyslipidemia and hypertension, were more prevalent in the subjects with NAFLD than in the controls. Therefore, we should try to assess the status of the metabolic diseases, and treat them in patients with NAFLD.
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Effects of Tibolone and Active Vitamin D Combined Treatment on Bone Mineral Density in Korean Postmenopausal Women.
Se Hwa Kim, Yu Mie Rhee, Soo Kyung Kim, Dae Jung Kim, Hyeung Jin Kim, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Kyung Rae Kim, Hyun Chul Lee, Gap Bum Huh, Sung Kil Lim
J Korean Endocr Soc. 2002;17(4):535-543.   Published online August 1, 2002
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BACKGROUND
Tibolone is a novel synthetic compound with tissue-specific effects in bone, breast tissue and the endometrium. Tibolone, and active vitamin D, effectively prevent bone loss, and the maintain skeletal integrity of postmenopausal women. The aim of the present study was to examine the effect of tibolone, and active vitamin D (1-hydroxyvitamin D3), therapies given alone, or in combination, against bone loss in postmenopausal women. METHODS: One hundred and three postmenopausal women were treated with tibolone (n=40), alphacalcidol (n=27) or both drugs (n=36) for 12 months. All subjects took supplemental calcium carbonate (500 mg daily). The bone mineral densities (BMD) of the lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry (DXA) at the baseline and after 12 months. RESULTS: Tibolone therapy produced significant increase of 4.1 and 1.8% in the BMD at the lumbar spine (p<0.001) and femoral neck (p=0.009), respectively. The combination of tibolone and active vitamin D increased the BMD by 8.0 and 4.4% (p<0.001) at the spine and femoral neck, respectively. The differences in the change of BMD from the baseline at the lumbar spine was significant (p=0.038) in the combination treatment group compared that in the tibolone alone group. CONCLUSION: Tibolone alone, and in combination with active vitamin D, effectively increased the BMD at all skeletal sites in postmenopausal women. Combination treatment for osteoporosis is emerging as a promising modality in Korean postmenopausal women.
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The Inhibitory Effect of the Second Generation Sulfonylurea Drugs on Cytochrome P450-catalyzed Reaction by Human Liver Microsomes.
Jee Yee Choi, Su Young Kim, Kyoung Ah Kim, Ji Young Park
J Korean Endocr Soc. 2002;17(4):544-553.   Published online August 1, 2002
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BACKGROUND
Sulfonylurea drugs have been used for many decades as one of the main families of drugs for the treatment of type 2 diabetes mellitus. Even though there are many opportunities to medicate sulfonylurea drugs concomitantly with many other drugs, and furthermore there have been several case reports on drug interactions with sulfonylurea drugs, there has been no clear demonstration revealing the mechanisms that cause these interactions. We therefore evaluated inhibitory potential of sulfonylurea drugs, including glibenclamide, glipizide and gliclazide, on the cytochrome P450 (CYP)-catalyzing enzymes using human liver microsomes. METHODS: The inhibitory effects of glibenclamide, glipizide and gliclazide, on the CYP-catalyzing reaction, were evaluated for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 using human liver microsomes, and probe drugs for each. RESULTS: Glibenclamide showed relative potent inhibitory effects on the CYP2C9- and CYP3A4-catallyzed reaction (IC50; 11.3 ( microM and 59.0 ( microM). The other CYP isoforms tested showed only weak inhibitory effects by due to glibenclamide (IC50 > 112 ( microM). Glipizide showed potent inhibitory effect on CYP3A4-catalyzed reaction only (IC50; 11.2 ( microM), and weak, or no, inhibitory effects on each on the other CYP isoforms tested (IC50 > 276 ( microM). CONCLUSION: The sulfonylurea drugs showed inhibitory potential on the CYP-catalyzing reaction in human liver microsomes. The results obtained in the present study provide insights into the potential of the drug interaction to ward drugs co-administered with sulfonylureas. It will be necessary to take into consideration the control of blood glucose, as well as therapeutic drug monitoring, to reduced toxicities when sulfonylurea drugs are co-administered with drugs of a narrow therapeutic range, or with severe dose-dependent toxicities.
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Clinical Study of the Pheochromocytoma.
Dong Hyun Shin, Sin Gon Kim, Dong Rim Kim, Nan Hee Kim, Kyung Mook Choi, Saih Yun Baik, Dong Seop Choi, Sung Ock Suh
J Korean Endocr Soc. 2002;17(4):554-563.   Published online August 1, 2002
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BACKGROUND
Pheochromocytoma may arise within the adrenal medulla, or in other locations where sympathetic ganglia or chromaffin tissues are known to exist. Approximately 0.1% of hypertensive patients have pheochromocytoma. Most of this hypertension can be cured by surgical removal of the tumor, but lethal complication can develop if proper treatment is not prepared. Therefore, accurate diagnosis and preoperative preparation is very important. The objective of this study was to evaluate the clinical characteristics of pheochromocytoma and the blood pressure change following tumor removal. METHOD: The medical records of 45 patients [29 cases of intra-adrenal, 16 cases of extra-adrenal (paraganglioma)] diagnosed with of pheochromocytoma at Korea University Medical Center between 1991 and 2001 were reviewed. RESULTS: Twenty of the cases were male and 25 were female. The mean age of these patients was 43 years old. Hypertension, headaches, palpitations and impaired glucose tolerance were observed more frequently in cases of intra-adrenal tumor than in those of extra-adrenal. In the extra-adrenal group, abdominal pain, hypertension and nausea were more frequently observed. A biochemical study showed that the sensitivity of the test for catecholamines and metabolites in 24 hours urine was over 80%. For the localization of tumors we used abdominal CT and MIBG. The sensitivities of the CT and MIBG for the tumor localization were 97 and 91%, respectively. Blood pressures during the operations were effectively controlled by preoperative treatment with phenoxybenzamine (non-competitive, non-selective -adrenoreceptor antagonists). CONCLUSION: Surgical treatment cured 23 of the 30 cases of hypertension with pheochromocytoma. We have to take careful approaches in the care of the patient who may have pheochromocytoma, due to the various clinical signs and symptoms.
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Case Reports
A Case of Klinefelter's Syndrome with Rathke's Cleft Cyst.
Hyun Joo Lee, Hyo Kyoung Park, Dae Jung Kim, Yu Mie Rhee, Chul Woo Ahn, Sang Soo Jung, Jae Hyun Nam, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Yong Koo Park, Hyun Chul Lee, Kap Bum Huh
J Korean Endocr Soc. 2002;17(4):564-571.   Published online August 1, 2002
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Klinefelter's syndrome is one of the most common forms of primary hypogonadism presenting with gynecomastia, azospermia and increased follicle-stimulating hormone. It is well known that this syndrome has an increased incidence of neoplasia, especially breast cancer and extragonadal germ cell tumors. However, it is rarely associated with an intracranial tumor of maldevelopmental origin, especially in the suprasellar area. We report, for the first time, a case of Klinefelter's syndrome, with a Rathke's cleft cyst is the patient was a 32-year-old male who was known to have an incidentaloma form brain computed tomography, which was clinically diagnosed as a suprasellar tumor. After operating, the suprasellar mass was confirmed as a Rathke's cleft cyst, and his hormonal abnormality, an elevated level of follicle-stimulating hormone, was not normalized. Therefore, we performed chromosomal analysis, and diagnosed Klinefelter's syndrome with the XXY karyotype.
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A Case with Thyroid Tuberculosis Diagnosed by Non-operative Method.
Dong Hun Lee, Hee Sun Chung, Hyoung Suk Lee, Mee Jung Kim, Jung Eun Kim, Yoon Sok Chung, Kwan Woo Lee, Hyeon Man Kim
J Korean Endocr Soc. 2002;17(4):572-575.   Published online August 1, 2002
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Tuberculosis of the thyroid gland is extremely rare, with a few surgically removed cases having been reported. The differential diagnosis, from malignancies and other non tuberculous granulomatous lesions, is impossible clinical grounds. We experienced a case of tuberculosis of the thyroid gland with palpable thyroid nodules, in a 23 year-old female patient. She was clinical and biochemically euthyroid. US and CT scans demonstrated a low density mass in the left low lobe of the thyroid gland. An FNAB showed caseous necrosis, and AFB stains demonstrated tuberculosis bacilli. We report a case of tuberculosis of the thyroid gland, diagnosed by a non-operative method.
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A Case of Acute Suppurative Thyroiditis as a Complication of Acupuncture in Patient with a Benign Thyroid Nodule.
Tae Yong Kim, Han Mo Yang, Jae Kyung Hwang, Young Min Cho, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho
J Korean Endocr Soc. 2002;17(4):576-582.   Published online August 1, 2002
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Acute suppurative thyroiditis is an uncommon disease, and usually affects patients with preexisting thyroid gland pathology. Penetrating injury could provide an acquired channel for the infection to spread into the relatively infection-resistant thyroid gland. We describe the first case of acute suppurative thyroiditis, as a complication of acupuncture, in a patient with a benign thyroid nodule. A 54-year-old male received acupuncture on his neck for the treatment of a previously diagnosed thyroid nodule. Four days after the acupuncture, the patient was admitted due to severe pain of the anterior neck and odynophagia. Fever and tenderness over the thyroid gland were observed. Burkholderia cepacia was isolated from a culture dish of aspirate of the thyroid gland. A neck computed tomography scan showed an abscess in the thyroid gland. Antibiotic treatment, and repeated drainage of the abscess, ameliorated the symptoms of infection. Two weeks after admission, the patient was discharged without sequela. Acupuncture should be considered as a kind of penetrating injury, which may induce acute suppurative thyroiditis.
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