Endocrinology and Metabolism

Volume 18(1); February 2003

Review Article

Role of Wnts, LRPs, and sFRPs in Bone.: Yoon Sok Chung; J Korean Endocr Soc. 2003;18(1):1-4. Published online February 1, 2003

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Abstract PDF: No abstract available.

Editorial

Genetics of Graves' Disease.: Jae Hoon Chung; J Korean Endocr Soc. 2003;18(1):5-11. Published online February 1, 2003

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Abstract PDF: No abstract available.

Original Articles

Vitamin D Receptor Gene 3' End Polymorphisms in Patients with Graves' Disease in Koreans.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Hui Su Lee, Young Joo Park, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Byung Doo Rhee, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):12-23. Published online February 1, 2003

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the association of vitamin D receptor (VDR) gene polymorphisms with Graves' disease in Koreans. We also investigated the association of VDR gene polymorphisms with the clinical characteristics and titers of TSH receptor antibodies in patients with Graves' disease. SUBJECTS AND METHODS: The VDR gene polymorphisms were evaluated in 117 patients with Graves' disease and 156 normal controls. The polymorphisms were represented according to restriction fragment length polymorphism; Aa(ApaI), Bb(BsmI) and Tt(TaqI), with the capital letters signifying the absence, and small letters the presence of restriction sites. RESULTS: The distribution of the ApaI polymorphism genotype was: AA(17.1%), Aa(50.4%) and aa(32.5%). The BsmI polymorphism genotype distribution was: BB(7.1%), Bb(35.4%) and bb(57.5%); and the TaqI polymorphism genotype distribution was: TT(92.6%), Tt(6.2) and tt(1.2%). No significant differences in either genotypic or allelic distributions were observed, between the patients with Graves' disease and the normal controls, associated with the VDR gene polymorphisms. No significant differences were observed with age, sex, size of goiter or the presence of ophthalmopathy, in patients with Graves' disease associated with the VDR gene polymorphisms. However, the titers of the TBII were significantly higher in the aa than the Aa genotype, and were also higher in the group without the A allele than in groups with(aa 55.9+/-18.3 vs. Aa 43.2+/-23.4, p<0.05; aa 55.9+/-18.3 vs. AA and Aa 42.9+/-23.5, p<0.05). Thyroid stimulating antibodies measured with a CHO cell transfected with a wild type of human TSH receptor, were also higher in patients without the A allele than in those with(aa 620+/-829 vs. AA and Aa 353+/-306, p<0.05). The titers of the anti-thyroglobulin antibodies were significantly higher in the groups not containing the B allele than in the group that did(bb 50.9+/-42.8 vs. BB and Bb 31.9+/-38.9, p<0.05). The serum alkaline phosphatase activities were higher in the group having the b allele than in the group that did not(Bb and bb 139+/-68 vs. BB 82.2+/-15.5, p<0.05). CONCLUSIONS: The VDR gene 3' end polymorphism was not associated with susceptibility to Graves' disease in Koreans. The studies of other polymorphism sites of the VDR gene might be required to elucidate the association of VDR gene polymorphisms with Graves' disease in Koreans.

Adequate Duration of Medical Therapy for Koreans with Graves' Disease.: Hyoung Suk Lee, Dong Hun Lee, Hee Sun Chung, Jong Woo Lee, Jung Eun Kim, Seung Soo Shin, Yoon Sok Chung, Kwan Woo Lee, Hyeon Man Kim; J Korean Endocr Soc. 2003;18(1):24-31. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Graves' disease is an organ specific autoimmune disease. Three kinds of therapeutic modalities(antithyroid drugs, ablation with radioactive iodine and subtotal thyroidectomy) are frequently performed for the management of this disease. The most popular therapeutic policy for the disease in Korea is antithyroid treatment. We analysed and compared the remission rates of all three modalities for Graves' disease, and evaluated the antithyroid modality to determine the correct duration of treatment. SUBJECTS AND METHODS: The medical records of 205 patients with Graves' disease were reviewed. For the evaluation of the antithyroid modality medical treatment, antithyroid drugs were administered for more than 1 year. The prognostic factors associated with remission were analysed by means of an ROC curve. RESULTS: 1) Of the 205 patients, proportions that received medical therapy, subtotal thyroidectomy and radioiodine therapy were 83.0, 14.1 and 2.9%, respectively. 2) The remission rates of the medical therapy, surgery and radioiodine therapy were 60.0, 96.5 and 83.0%, respectively. 3) The remission rate of the medical therapy was associated with the duration of medication and TBII activity. The determined proper duration for the antithyroid treatment was 26 months from the ROC curve analysis. CONCLUSION: The above results suggest that the proper duration of antithyroid treatment for Graves' disease is 26 months, after which time the subtotal thyroidectomy or radioiodine therapy should be considered if the disease has not remitted.

HLA, CTLA-4 and TNF-beta Gene Polymorphisms and Disease Susceptibility in Korean Children with Graves' Disease.: Moon Young Song, Min Ho Jung, Jun Seong Lee, Tai Gyu Kim, Sei Won Yang, Byung Churl Lee; J Korean Endocr Soc. 2003;18(1):32-44. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Graves' disease(GD) is an organ-specific autoimmune disorder that is inherited as a complex trait. At present three loci, namely the human leukocyte antigen(HLA), the cytotoxic T lymphocyte antigen-4(CTLA-4) and a thyroid stimulating hormone receptor(TSHR) are the only well-known genetic determinants for GD. To understand the mechanisms underlying the development of GD, we investigated the relationship of HLA alleles, polymorphisms of CTLA-4 gene and the tumor necrosis factor(TNF)-beta gene, with the disease susceptibility. METHODS: Fifty-two Korean children with GD(45 girls and 7 boys), and 119 healthy children, were investigated in this study. The HLA alleles were determined by a standard lymphocyte microtoxicity technique, ARMS-PCR(Amplification Refractory Mutation System-Polymerase Chain Reaction), PCR-SSP(Sequence Specific Primer) and PCR-SSOP(Sequence Specific Oliogonucleotide Probe) method. The CTLA-4 gene polymorphism was analyzed by PCR-SSCP(Single Strand Conformation Polymorphism), and the TNF-beta gene polymorphism by PCR-RFLP(Restriction Fragment Length Polymorphism). RESULTS: (1) The frequencies of HLA-A2, B46, DRB1*08 and DPB1*0202 were significantly increased, and those of HLA-A24, DQA1*01 and DQB1*05 were significantly decreased, in the GD patients compared to the control subjects. (2) A significant difference in the distributions of the AA, AG, and GG genotypes of the CTLA-4 exon 1 were observed between the GD patients and the control subjects, and a significant increase in the frequency of the G (alanine) allele was seen in the GD patients compared with the control subjects(84.6% vs 63.4%; RR=3.2; p<0.0001). A significant difference in the distributions of the AA, AG, and GG genotypes of the CTLA-4 exon 1 was observed between the GD patients with and without exophthalmos. A significant increase in the frequency of the G allele was seen in the GD patients with exophthalmos compared to those without(94.0% vs 75.9%; RR=7.0; p<0.05). (3) No significant difference in the distributions of the 1/1, 1/2 and 2/2 genotypes, and the 1 and 2 alleles of TNF-beta was observed between the GD patients and the control subjects. No significant difference in the distributions of the 1/1, 1/2, and 2/2 genotypes and the 1 and 2 alleles of TNF-beta were observed between the GD patients with or without exophthalmos but a significant increase in the frequency of the 2/2 allele was seen in the GD patients having TSHRAb > or =45% compared with GD patients having TSHRAb <45%(37.5% vs 3.6%; RR=14.8; p<0.01). CONCLUSION: These data suggest that HLA-A2, B46, Cw*0102, DRB1*08 and DPB1*0202 are markers for disease susceptibility, and that HLA-A24, DQA1*01 and DQB1*05 are markers for disease protection, in Korean children with GD. This study showed that the CTLA-4 gene polymorphism was an additional marker of susceptibility in the GD patients, and was associated with exophthalmos, and that the TNF-beta gene polymorphism was associated with the TSHRAb activity.

Regulatory Mechanism of p66 Shc Expression by TSH in FRTL-5 Cells.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Yun Yong Lee, Seon Hwa Lee, Do Joon Park, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):45-55. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Thyroid goiters are very common, however, the mechanism of development is not fully understood. A TSH receptor has been known to activate two different signaling pathways the cAMP/protein kinase A(PKA) and phospholipase C(PLC)/protein kinase C(PKC) systems. However, both systems are limited in the degree to which they explain the discrepancy between a goiter and TSH receptor activation. It has recently been reported that the expression of p66 Shc was increased by TSH stimulation in thyrocytes, suggesting that the p66 Shc molecule may play a critical role in the transition of the TSH-induced growth signals. METHODS AND RESULTS: In this study, we examined the expression of p66 Shc by stimulation of TSH, and the regulatory mechanisms of the TSH-induced expression of the p66 Shc in FRTL-5 cells. In FRTL-5 cells, TSH could increase the expression of the p66 Shc, and the this expression was decreased to basal levels after the removal of TSH. The TSH-induced p66 Shc expression was competitively inhibited by TSH receptor blocking antibodies. The increments of the expression of the p66 Shc protein caused by TSH were both time and concentration dependent, and it was same in the mRNA levels. Cholera toxin increased the expression of the p66 Shc, while pertussis toxin did not. The activators of the cAMP/PKA pathway (8-bromo-cAMP and forskolin) also stimulated the expression of p66 Shc, and the PKA inhibitor H89 decreased the expression, while the inhibition of the PKC pathway by GF109203X, or PMA, affected the expression of p66 Shc very little. CONCLUSION: Our data suggests that p66 Shc may play an important role in regulating the growth of thyrocytes. The TSH receptor - Gs protein - adenylate cyclase - cAMP - PKA pathway mainly mediates the TSH effects on the expression of p66 Shc molecules.

The Effects of Alendronate in Bone Metabolism of Primary Osteoporosis.: Hyo Jeong Kim, Jee Won Park, Soo Jin Kim, Kwan Woo Lee, Hyeon Man Kim, Yoon Sok Chung; J Korean Endocr Soc. 2003;18(1):56-62. Published online February 1, 2003

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Abstract PDF: BACKGROUND
To evaluate the effects of alendronate in preventing bone loss at the spine and hip in Korean cases of primary osteoporosis, we treated 138 patients with 10 mg of alendronate daily. Of the 138 patients treated, 50 were treated for one complete year, and at their final visit, measurements were taken to assess the completed outcome of the reatment, and the results from this small group were compared with those of the rest. The way this has been written causes ambiguity concerning exactly who was being studied. Check that my rewrite of this section conveys correctly the group that was studied, and how. METHODS: The serum levels of calcium(Ca) and phosphorous(P), total alkaline phosphatase(ALP), the urine calcium creatinine ratio(Uca/cr) and urine deoxypyridinoline(DPD) were measured before, during, and after the 1 year treatment period. The bone mineral densities(BMDs) at the spine and hip were also measured before and after the treatment period. New clinical fractures and side effects, were evaluated during the treatment period. RESULTS: The total serum ALP and urine DPD were decreased significantly, after the treatment period, by 38.3 and 40.5% respectively. The bone mineral density at the spine and hip were significantly increased after 1 year, by 6.7 and 2.0%, respectively. Of the 50 subjects who had completed a full year of treatment, only 4(8%) had developed new clinical fractures. Of the 138 patients who had been treated, 8(5.8%) discontinued the medication due to side effects. Of these, 7 had gastrointestinal symptoms, and 1 had skin eruption. CONCLUSION: Alendronate significantly decreased the total serum ALP and urine DPD and significantly increased spine and hip bone mineral density. Alendronate 10mg was effective in preventing bone loss in Korean cases of primary osteoporosis.

Randomized Controlled Trial

The Effect of Intensive Education on Glycemic Control in Type 2 Diabetic Patients.: Youn Wook Lee, Won Sun Hwang, Sun Jung Choe, Dong Hun Lee, Doh Hyun Kim, Eun Hee Lee, Eun Gyoung Hong, Hye Lim Noh, Yoon Sok Chung, Kwan Woo Lee, Hyeon Man Kim; J Korean Endocr Soc. 2003;18(1):63-72. Published online February 1, 2003

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Abstract PDF: BACKGROUND
To this date, efforts to develop effective methods for the education of diabetic patients have been limited. The important goal of self-management and weight control for diabetic treatment can not be attained without long and intensive period of education. This study was undertaken to assess the effectiveness of an intensive educational program, of behavior and diet control, which was carried out on subjects with type 2 diabetes, on an out-patient basis. We compared the effectiveness of an intensive education programme with that of a conventional education programme for the self-management of type 2 diabetic patients. METHODS: Subjects with type 2 diabetes were randomly selected, and allocated to one of two groups. One group received a conventional education programme of self-management(the CE group), and the second group received an intensive education programmes for three months, after which the effectiveness of the programmes were evaluated. RESULTS: 1) The levels of fasting blood sugar(FBS), postprandial 2 hour blood sugar(PP2h) and HbA1c were significantly lowered in both groups following the intervention(p<0.05). In the IE group, the FBS declined from 12.4nmol/L to 7.7nmol/L, PP2h declined from 20.3nmol/L to 10.9nmol/L, and the HbA1c showed a similar decline from 9.4 to 7.0% after intervention(p<0.05). In the CE group, the FBS declined from 10.9 to 9.4nmol/l, the PP2h decreased from 17.1 to 14.6 nmol/l, and the HbA1c also decreased from 8.5 to 7.3% after intervention(p<0.05). The decrease in the FBS and HbA1c following the educational intervention was more pronounced in the IE group than the CE group (p<0.05). 2) The effectiveness of the education programmes in promoting appropriate dietary behavior in the diabetic subjects was assessed by a scoring system in three parts: a regularity score, a balance score and an attitude score. From a comparative study of the three scores, the patients attitudes were observed to be much improved in both the groups following the intervention compared to before the programmes, but the balance and total scores were significantly higher in the IE group than the CE group(p<0.05). CONCLUSION: We can conclude that the intensive diabetic education programme is more effective than a conventional programme, not only in improving the patients' levels of glucose, HbAlc, and dietary score, but also the diabetic patients self-control abilities, promoting behavioral change, and prompting problem solving capabilities in respect to the everyday problems that they have to face throughout their lives.

Case Reports

A Case of Raymond-Cestan Syndrome Caused by Inferior Petrosal Sinus Sampling.: Dong Hyeok Cho; J Korean Endocr Soc. 2003;18(1):73-78. Published online February 1, 2003

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Abstract PDF: Inferior petrosal sinus sampling (IPSS) plays an important role in the assessment of patients with ACTH-dependent Cushing's syndrome. IPSS has been described as an innocuous, essentially risk-free procedure. Neurological complications associated with IPSS are rare. Previously reported neurological complications include brain stem infraction, pontine hemorrhage and subarachnoid hemorrhage. A 26-year-old woman was admitted to the hospital because of a moon face and a buffalo hump. A MRI showed a suspicious, but uncertain, area on the left side of the sella turcica. IPSS was performed as an appropriate means of providing more information about the side of the ACTH source. Immediately after the procedure, the woman experienced double vision, caused by a complete sixth nerve palsy of the left eye, together with a contralateral hemiparesis. From a clinical point of view, abducens nerve palsy and contralateral hemiparesis corresponded to Raymond-Cestan syndrome. I report a case of Raymond-Cestan syndrome, following petrosal sinus sampling in a female patient with ACTH-dependent Cushing's syndrome. To the best of our knowledge, this complication associated with petrosal sinus sampling has only been described in one previous case report. Although IPSS may provide essential information in the investigation of Cushing's syndrome, the possibility of very occasional but devastating complications should be remembered.

A Case of Acute Rhabdomyolysis as a first Manifestation of Primary Hypothyroidism.: Jung Min Lee, Hyun Shik Son, Hye Jung Lee, Sook Hee Hong, Jong Min Lee, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; J Korean Endocr Soc. 2003;18(1):79-84. Published online February 1, 2003

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Abstract PDF: Various symptoms, such as bradycardia, hypotension, fatigue, constipation, myalgia, muscle weakness, delayed tendon reflex, and so forth, presented in hypothyroidism. Of these symptoms, muscle weakness, myalgia, and delayed tendon reflex are common features of hypothyroid myopathy. Acute rhabdomyolysis, a very severe form of myopathy, but is a rare manifestation of primary hypothyrodism. A 29-year-old man developed acute rhabdomyolysis, associated with primary hypothyroidism as a first manifestation. After thyroxine replacement therapy, he exhibited some improvement in muscle weakness and in non-pitting edema. We report a case of primary hypothyroidism presenting with spontaneous rhabdomyolysis as a first manifestation.

A Case of Multiple Endocrine Neoplasia Type 2B associated with a M918T Mutation in RET Proto-Oncogene.: Tae Yong Kim, Jae Kyung Hwang, Min Kyong Moon, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Yo Kyu Yoon, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):85-93. Published online February 1, 2003

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Abstract PDF: A multiple endocrine neoplasia type 2B(MEN2B) is the most distinct and aggressive form of the MEN type 2 variants. We report a case of a 24-years-old woman with MEN2B. The patient had previously undergone a Duhamel's operation due to a megacolon at 6 years old, minor surgery to remove small tumors on the lip at 8 years old, and a bilateral osteotomy of the femur, due to coxa valga, at 15 years old. She underwent a total thyroidectomy and neck dissection, due to a growing thyroid nodule, despite thyroxine treatment, at 19 years old. The pathology revealed a medullary thyroid carcinoma. There was no history of MEN 2B in her family. She had prominent lips, multiple oral mucosal masses, and marfanoid habitus. During the subsequent follow-up, a positron emission tomogram was taken due to a persistently high level of serum calcitonin, despite repeated neck dissections, which revealed a mass in the right adrenal gland. Adrenomedullary function tests showed high levels of urinary catecholamine metabolites, and a genetic analysis of the peripheral leukocyte showed a codon 918 mutation (Met918Thr) at exon 16 of the RET proto-oncogene. The patient underwent a right adrenalectomy and the pathology revealed a pheoch-romocytoma.

A Case of Fuctioning Extraadrenal Paraganglioma Mimicking Acute Coronary Syndrome.: Tae Hee Lee, Yeon Ah Lee, Tae Wook Woo, Gwan Pyo Koh, Cheol Young Park, Jung Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2003;18(1):94-99. Published online February 1, 2003

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Abstract PDF: A functioning paraganglioma is a rare catecholamine-producing tumor that arises from the extra-adrenal chromaffin tissue. Recently we experienced a case in which a 42 year-old male patient with a functioning extra-adrenal paraganglioma mimicked an acute coronary syndrome. A functioning extra-adrenal paraganglioma was diagnosed by means of a biochemical study and a radiological imaging study. After stabilizing his blood pressure, using alpha adrenergic blocker, we successfully removed a 6?cm sized paraganglioma from between the aorta and the IVC in the retroperitoneal space.

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