Endocrinology and Metabolism

Volume 19(2); April 2004

Original Articles

Inflammation and Obesity.: Cheol Young Park, Hyung Joon Yoo; J Korean Endocr Soc. 2004;19(2):97-108. Published online April 1, 2004

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Abstract PDF: No abstract available.

RNAi: A Powerful Reverse Genetic Tool.: Yeon Soo Kim; J Korean Endocr Soc. 2004;19(2):109-119. Published online April 1, 2004

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Abstract PDF: No abstract available.

The Measurement of Serum Thyroglobulin Levels.: Young Joo Park; J Korean Endocr Soc. 2004;19(2):120-126. Published online April 1, 2004

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Abstract PDF: No abstract available.

Effects of USF-1, USF-2, PTEN and Thyroid Transcription Factors on the Function and Growth in FRTL-5 Cells.: Yun Jae Chung, eun Sook Kim, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2004;19(2):127-140. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Upstream stimulatory factors (USFs) and PTEN are known to be tumor suppressants. USFs and PAX-8 were reported to be the functional competitors in sodium iodide symporter (NIS) gene expression. We investigated the effects of USF-1, USF-2, PTEN, and thyroid-specific transcription factors (TTF-1, PAX-8) on the function and growth of thyrocytes of FRTL 5 rat thyroid cells. METHODS: Complementary DNAs of the USF-1, USF-2, PTEN, TTF-1 (homeodomain), and PAX-8 were synthesized from RNA extracted from FRTL-5using an RT-PCR kit. Each of them was transiently transfected to the FRTL-5 cells using the lipofectamine after being cloned into the pcDNA3.1 vectors. Stable cell lines, which were transfected by USF-1, PTEN, TTF-1, and PAX-8, were also obtained from the FRTL-5 cells, respectively. Extracellular cAMP concentrations were measured after 24 hours of incubation with varying concentrations of bTSH (0.1~100 mIU/mL). After, [Methyl-3H] thymidine uptake or 5-bromo-2'-deoxyuridine (BrdU) assay was performed. RESULTS: USF-1 and USF-2 significantly increased cAMP levels and decreased thymidine uptake in both transiently and stably transfected cells (p<0.01). PTEN had a tendency to increase both the cAMP levels and BrdU uptake in stable cells, but had a tendency to decrease thymidine uptake in transiently transfected cells. TTF-1 significantly increased the cAMP levels and either thymidine or BrdU uptake in both transiently and stably transfected cells (p<0.05). PAX-8 significantly increased both the cAMP levels and BrdU assay in stable cells, but in transiently transfected cells, it significantly decreased cAMP concentrations (p<0.01). CONCLUSIONS: These results suggested that both the USF-1 and USF-2 play a role in suppressing the growth of thyrocytes but at the same time, they kept the ability to produce cAMP after TSH stimulation. They had opposing effects on TTF-1 and PAX-8 in terms of the proliferation of thyrocytes

The Aging-related Change of Responses to TSH in Thyroid Cells.: Young Joo Park, Tae Yong Kim, Ji Eun Kim, Young Cheol Kim, In Kyeong Chung, Chan Soo Shin, Do Joon Park, Kyoung Soo Park, Seong Yeon Kim, Sang Chul Park, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2004;19(2):141-151. Published online April 1, 2004

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Abstract PDF: BACKGROUND
To understand the mechanism of aging-related changes of the thyroid, the differentiated functions and growth of thyroid cells in response to TSH were investigated using aged or young thyrocytes. METHODS: FRTL-5 cells, with less than 10 or more than 45 passages, were used. After treatment with 1 U/L TSH or 1-100 mM NaI, the cAMP generation, iodide uptake, cellular proliferation or the expression of NIS mRNA or protein were measured. Sprague-Dawley rats were sacrificed at 5 and 16 weeks and 23 months, and their thyroids used for Northern blot analysis or immunohistochemistry of NIS. RESULTS: There were no differences in cAMP generation, iodide uptake, the proportions of G1/M or S phase, or intracellular DNA contents between the young and aged cells at basel levels. After TSH stimulation, these were increased in dose-dependent manners, with larger increments in the young cells. The changes in the NIS mRNA expression were similar in both the young and aged cells, but to a greater extent in the young cells. A similar phenomenon was observed in rat. However, the amount or intracellular distribution of NIS protein was not different. There was also no difference in the function or expression of NIS after treatment with a high dose of iodide. CONCLUSION: The aging-related decrease in the generation of cAMP might be thought of as one of the mechanisms of the decrement of iodide uptake or cellular proliferation with aging. The decreased expression of NIS mRNA seems to be the most important mechanism for the decreased iodide uptake capacity

Regulation of Prolactin Gene Expression by Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Female Rat Pituitary Gland.: Young Il Kim, Tae Young Ha, Eun Sook Kim, Il Seong Nam-Goong, M S O'Dorisio, Min Kyu Hur, Sang Kyu Park; J Korean Endocr Soc. 2004;19(2):152-164. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process

Relationship between The Expressions of Sodium/Iodide Symporter and The Findings of Thallium-201 Scan in Thyroid Nodules.: Joon Hyop An, Min Ah Na, Sang Soo Kim, Ok Nyu Kong, Ju Won Seok, Chang Hun Lee, Chang Won Lee, In Joo Kim, Yong Ki Kim; J Korean Endocr Soc. 2004;19(2):165-174. Published online April 1, 2004

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Abstract PDF: BACKGROUND
The sodium/iodide symporter (NIS) has an important role in the diagnosis and treatment of well differentiated thyroid carcinoma. The relationship between the uptake of thallium- 201 scan (201Tl scan) and the expression of sodium/iodide symporter (hNIS) was studied in thyroid nodules. METHODS: Patients that had undergone operations for thyroid nodules, and who received a 201Tl scan before their operations, were investigated. Anti-NIS antibodies were used to analyze the presence and distribution of the hNIS protein by immunohistochemical staining of their thyroid tissues. RESULTS: Forty-four patients (papillary carcinoma; 18, follicular adenoma; 11, adenomatous goiter; 14, nonspecific thyroiditis; 1) 30 with no immunoreactivity and 14 with a positive reaction to the anti-NIS antibody, were included. The NIS negative patients (12/30) had no 201Tl uptake, but all others were positive on 201Tl scan, and the NIS-positive patients (13/14) had positive 201Tl uptake, with 1 negative on 201Tl scan, with significant difference (p=0.035). Of the 18 patients with a papillary thyroid carcinoma, the NIS negative patients (2/10) had no 201Tl uptake and the others were positive on 201Tl scan, but without significant difference. NIS positive patients (1/8) with a papillary thyroid carcinoma had no 201Tl uptake, and the others were positive on 201Tl scan, but without significant difference. Whether the results of NIS staining and 201Tl scan were positive or not did not affect the responses of radioactive iodine therapy in our study. CONCLUSION: These results suggest that thallium-201 uptake may be correlated with hNIS expression in thyroid nodules

Electrocardiographic Changes after Hormone Replacement Treatment in Patients with Sheehan's Syndrome.: Kyoung Hee Kweon, Chang Hun Lee, Byoung Hyun Park, Chung Gu Cho; J Korean Endocr Soc. 2004;19(2):175-180. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Electrocardiographic abnormalities were studied to find if they were reversible during adequate hormonal treatment and to investigate regional inhomogenicity of ventricular repolarization in patients with Sheehan's syndrome. METHODS: Eleven women with Sheehan syndrome, who treated with prednisolone and levothyroxine, were the subjects of this study. Before and after hormonal replacement, the plasma thyroxine, cortisol and resting standard EKG were checked RESULTS: The most frequent electrocardiographic finding was inversion or flattening of the T waves, which occurred in 10 patients, with QT prolongation (7 patients), ST depression (2 patients) being the other findings. After prednisolone and levothyroxine replacement, the T wave abnormalities were normalized in 8 patients (80%) and the ST depression all patients. The QT (437 27 msec vs. 379 29 msec, p<0.05) and QTc intervals (478 80 msec vs 403 73 msec, p<0.005) were shortened by hormone replacement. CONCLUSION: High incidences of electrocardiographic abnormalities, including T wave inversion or flattening, QT prolongation and ST depression, were noted in patients with Sheehan's syndrome. The majority of these abnormalities recovered due to hormone replacement. The QT and QTc interval values were significantly shortened after treatment. Therefore, the regional inhomogenicity of ventricular repolarization may recover with hormone replacement

The Effects of C161-->T Polymorphisms in Exon 6 of Peroxisome Proliferator-Activated Receptor- Gene on Bone Mineral Metabolism and Serum Osteoprotegerin Levels in Healthy Korean Middle-aged Men.: Eun Jung Rhee, Won Young Lee, Se Yeon Kim, Eun Sook Oh, Ki Hyun Baek, Ki Won Oh, Kyung Chang Park, Ki Ok Han, Hyun Koo Yoon, Moo Il Kang, Sun Woo Kim; J Korean Endocr Soc. 2004;19(2):181-193. Published online April 1, 2004

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Abstract PDF: BACKGROUND
The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p<0.05) than those with the CC genotypes. There were no differences in the bone turnover markers between the different genotypes (p>0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (p<0.05). When the subjects were divided into 3 groups, i.e., normal, osteopenic and osteoporotic groups, according to the lumbar spine BMD, the group with the T allele had a significantly higher prevalence of osteopenia and smaller numbers with normal BMD than those with the CC genotype (p=0.032). CONCLUSION: The frequencies of the C161-->T substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis

A Clinical Observation on Twelve Cases of Primary Aldosteronism.: Seung Chul Cho, Yong Soo Park, Hwon Gyum Park, Sung Hee Lee, Soon Gil Kim, Woong Hwan Choi, Yu Hern Ahn, Pa Jong Jung, Tae Wha Kim; J Korean Endocr Soc. 2004;19(2):194-202. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Primary aldosteronism describes a group of disorders characterized by long-standing aldosterone excess, with suppressed renin activity, resulting in hypertension and hypokalemia. The protean clinical and biochemical characteristics of this syndrome have important implications regarding its pathophysiology and responsiveness to treatment. METHODS: The cases of 12 primary aldosteronisms, diagnosed at Hanyang University Hospital between 1996 and 1999, were reviewed. RESULTS: The 12 cases were composed of 9 aldosterone-producing adenoma, 2 adrenal hyperplasia and a case of idiopathic hyperaldosteronism. There were 9 women and 3 men. The mean age was 46 yrs (range, 23 to 64 yrs). At the initial visit, the mean blood pressure was 160+/-26/104+/-14 mmHg, and one case of idiopathic hyperplasia had normal blood pressure. The mean serum K+ level was 2.6+/-0.5 mEq/L (range, 1.5 to 3.5 mEq/L). The mean plasma renin activity and plasma aldosterone concentration were 0.4+/-0.4 ng/ml/hr (range, 0.2 to 1.6 ng/ml/hr) and 407.5+/-199.8 pg/mL (range, 225 to 800 pg/mL), respectively. Different steps of diagnostic modalities were applied for the preoperative differential diagnosis. All patients, with the exception of the one with idiopathic hyperaldosteronism, were managed by a unilateral laparoscopic adrenalectomy, as they were all diagnosed under the impression of adrenal adenomas. Ultimately, 9 cases were proven to have adrenal adenomas. One hypertensive case, with hypokalemia, had adrenal hyperplasia, and the case with normotension was found to have adrenal nodular hyperplasia from the pathology. The size of the tumors ranged from 1.4 to 2.4 cm in diameter. Among the 11 cases that underwent an adrenalectomy, the blood pressures in 6 cases normalized after the operation, while the other 5, including the one with unilateral hyperplasia, were still in need of antihypertensives for the control of elevated blood pressures, even after the operation. The other case of idiopathic hyperaldosteronism was managed by the prescription of spironolactone. CONCLUSION: From these, it can be suggested that the clinical diversity of the syndrome, especially in the pathophysiology and response to operation, awaits the development of a better preoperative lateralization procedure

Case Reports

A Case of Myxedema Coma with Severe Hypoventilation.: Jin Young Shim, Seung Won Lee, Hyun Woo Lee, Joon Hyuck Choi, Young Jun Song, Hyoung Suk Lee, Yoon Sok Chung, Kwan Woo Lee; J Korean Endocr Soc. 2004;19(2):203-208. Published online April 1, 2004

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Abstract PDF: A myxedema coma, representing the extreme feature of hypothyroidism is rare. Despite early vigorous treatment, a myxedema coma is associated with a mortality rate as high as 60%. Herein, a case of a myxedema coma, with severe hypoventilation, is described. When the patient arrived at the emergency room, she complained of dyspnea and general weakness, and was of a drowsy mental status. 7 days after admission, she was more confused and disoriented, and respiratory insufficiency had developed. Although levothyroxine was continued and her respiration improved, she still had a confused mentality and seizure developed. Despite medication her consciousness did not improve, so was discharged in despair by her family members. The respiratory abnormality with a myxedema coma is a depressed ventilatory response to hypercapnea, resulting in a decrease in alveolar ventilation, with progressive CO2 retention. An upper airway obstruction, especially during sleep, and neuromuscular dysfunction in breathing may be shown in hypothyroidism. Therefore, a myxedema coma, accompanied by severe hypoventilation, should be intensively treated with thyroid hormone replacement therapy and mechanical ventilatory support

A Case of Thyroid Papillary Cancer Associated with Familial Adenomatous Polyposis.: Sung Jae Shin, Hyun Joo Lee, So Hun Kim, Wan Sub Shim, Sihoon Lee, Yoo Mee Kim, Yumie Rhee, Tae Il Kim, Bong Soo Cha, Hyun Chul Lee, Sung Kil Lim; J Korean Endocr Soc. 2004;19(2):209-216. Published online April 1, 2004

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Abstract PDF: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome, typically characterized by multiple colorectal adenomas and increased incidence of colorectal carcinomas if left untreated. It is caused by germline mutations of the adenomatous polyposis coli (APC) gene, which has been mapped on chromosome 5q21, and is accompanied by various benign and malignant extracolonic manifestations. The prevalence of thyroid tumors developing in patients with FAP is about 1~2%, are associated with FAP and have certain characteristics; mean age of tumor diagnosis at less than 30 years of age, the pathology is the papillary histiotype in more than 90% of cases, including a so-called cribriform- morular pattern, and multifocality is a frequent feature. In a genetic analysis, thyroid cancer in FAP usually has a mutation in the 5-portion of exon 15 between 778 and 1309, on chromosome 5q21. Also, the ret/PTC (especially ret/PTC1 and ret/PTC3) and p53 genes are thought probably to be associated with thyroid cancer in FAP patients. A case of familial adenomatous polyposis, accompanied by thyroid papillary cancer, was experienced in a 29 year-old female. She had hundreds of adenomas throughout the entire colon and congenital hypertrophy of the retinal pigment epithelium (CHRPE). The pathological finding of thyroid cancer was revealed as a mixture of cribriform, trabecular and papillary patterns. In a genetic analysis, she and her brother had a germline mutation of the APC gene at codon 1309. In Korea, there has been no previous case of cribriform-morular pattern and familial genetic analysis in FAP associated with thyroid cancer. Therefore, this case is reported, with a review of the literature

A Case of Acute Adrenal Insufficiency with Bilateral Adrenal Hemorrhagic Infarction due to Ebstein-Barr Virus Infection in a Patient with Asymptomatic Chronic Adrenal Insufficiency.: Sung Chang Chung, Soon Hong Park, Joo Young Lee, Shin Won Lee, Gui Hwa Jeong, Sun Zoo Kim, Han Ik Bae, Hun Kyu Ryeom, Jung Guk Kim, Young Oh Kweon, Sung Woo Ha, Bo Wan Kim; J Korean Endocr Soc. 2004;19(2):217-222. Published online April 1, 2004

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Abstract PDF: Acute adrenal insufficiency may result from adrenal crisis, hemorrhagic destruction, or the rapid withdrawal of steroids from patient with chronic steroid medication, congenital adrenal hyperplasia or those on other drugs. Acute hemorrhagic destruction of both adrenal glands can occur due to infection, trauma, anticoagulant therapy, antiphospholipid syndrome or a coagulation disorder. However, there have been no reports on acute hemorrhagic adrenal insufficiency due to the Ebstein-Barr virus (EBV). Herein, a case of acute adrenal insufficiency, with bilateral adrenal hemorrhagic infarction, is reported in a patient with asymptomatic chronic adrenal insufficiency. A 42-year-old man presented with general weakness, weight loss and hyperpigmentation of several months duration. He suffered from a sore throat, general myalgia and a headache on admission. The laboratory findings were lymphocytosis, positive EBV IgM antibody, low cortisol level and a high level of adrenocorticotropic hormone (ACTH). Adrenocortical autoantibody and PCR for Mycobacterium tuberculosis showed negative findings. The serologic findings for CMV and HIV were negative. Fine needle aspiration of the adrenal gland revealed a hemorrhagic infarction and positive staining for the anti-EBV antibody. Acute adrenal insufficiency was then diagnosed with a bilateral adrenal hemorrhagic infarction due to the EBV infection in the patient, also with asymptomatic chronic adrenal insufficiency. This is the first case of acute adrenal insufficiency with bilateral hemorrhagic infarction, due to an EBV infection

A Case of Hepatomegaly due to Diabetic Glycogenosis Reversed by Glycemic Control.: Jina Park, Dae Hoon Song, Jong Suk Park, Joo Young Nam, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Hae Ryoung Kim, Chan Il Park; J Korean Endocr Soc. 2004;19(2):223-228. Published online April 1, 2004

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Abstract PDF: Diabetes mellitus is well known to be associated with various structural and functional liver abnormalities. If diabetic patients are accompanied by hepatomegaly or abnormal findings from a liver function test, the most common pathological findings are steatosis and glycogenosis. The steatosis is characterized by deposition of macrovesicular fat droplets in the hepatocytes, which is common in obese, type 2 diabetes mellitus. If macrovesicular steatosis is combined with mixed inflammatory infiltrate, without evidence of alcoholic hepatitis, the case could be diagnosed as nonalcoholic steatohepatitis (NASH). NASH has the possibility of progressing to cirrhosis. Secondary glycogenosis is common in uncontrolled type 1 diabetes mellitus, and is completely reversible. A 22-year-old male, with uncontrolled type 1 diabetes mellitus, was admitted with anorexia, nausea and right upper quadrant pain. Hepatomegaly and elevated aminotransferases were noted. He was diagnosed as diabetic glycogenosis using computed tomogram and liver biopsy. The hepato megaly and liver function test abnormalities were markedly improved with glycemic control

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