Endocrinology and Metabolism

Volume 12(1); March 1997

Original Articles

DHEA ( dehydroepiandrosterone ).: Yoon Sok Chung; J Korean Endocr Soc. 1997;12(1):1-7. Published online January 1, 2001

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Abstract PDF: No abstract available.

Subclinical Hypothyroidism.: Kwang Woo Lee; J Korean Endocr Soc. 1997;12(1):8-10. Published online January 1, 2001

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Abstract PDF: No abstract available.

Serum Lipoprotein (a) and Lipid Concentrations in Patients with Subelinical Hypothyroidism.: Kyoung Ah Kim, Jae Hoon Chung, Yeun Sun Kim, Kyu Jeung Ahn, Eun Mi Koh, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Jong Hun Lee, Kwang Won Kim; J Korean Endocr Soc. 1997;12(1):11-17. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Overt hypothyroidism is well-known cause of secondary hyperlipidemia and atherosclerosis. However, there have been dissenting reports of abnormalities in serum lipid concentrations in patients with subclinical hypothyroidism (SH). Recently, it has been reported that serum Lp (a) concentration, an independent risk factor of atherosclerosis, was increased in patients with SH. Therefore, we analyzed serum Lp (a) and other lipid concentrations to investigate whether they are increased in patients with SH and the correlation between serum Lp (a) and TSH concentrations. METHODS: We undertook this study in 53 patients with SH (TSH > 6 uiU/ml) and 197 age-and sex-matched healthy control subjects, They had no abnormalities in liver function, BUN, creatinine, fasting blood glucose, urinalysis, and past medical histories. Serum T3, T4, and TSH concentrations were measured by RIA using commercial kits. Serum concentrations of Lp (a), total cholesterol, triglyceride (TG), and HDL cholesterol (HDL-C) were measured by rate nephelometry and enzyme assay, respectively. RESULTS: There were no significant differences of serum Lp (a), total cholesterol, LDL cholesterol, TG, and HDL-C concentrations in 53 patients with SH and 197 control subjects (25.6+-3.8mg/dL vs. 25.4+-1.5mg/dL ; 204.0+-4.2mg/dL vs. 204.0+-2.4mg/dL ; 127.0+-3.9mg/dL vs. 125.0+-2.3 mg/dL ; 133.0+-8.5mg/dL vs. 130.0+-6.0mg/dL ; 50.0+-1.5mg/dL vs. 53.0+-0.9mg/dL). There was no correlation between Lp (a) and TSH concentrations in SH (r=0.12, p>0.05). CONCLUSION: Serum Lp (a) concentration as well as total cholesterol, LDL cholesterol, and TG was not increased in patients with SH. There was no correlation between serum Lp (a) and TSH levels in subclinical hypothyroidism.

Measurements of Thyroid Stimulation Blocking Antibody Activities by Chinese Hamster Ovary ( CHO ) cells Expressing Human TSH Receptors in Patients with Primary Hypothyroidism.: Won Bae Kim, Bo Youn Cho, Do Joon Park; J Korean Endocr Soc. 1997;12(1):18-32. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The Chinese hamster ovary cells transfected with human TSH receptor cDNA (hTSHR-CHO), expressing functional human TSH receptors, are known to be more sensitive in detection of thyroid stimulating antibodies than FRTL-5 cells. There has been no report on the usefulness of these cells to measure thyroid stimulation blocking antibody (TSBAb) activity which is frequently found in patients with primary myxedema, METHODS: We established the optimal assay condition of measurement of TSBAb using hTSHR-CHO cells, and simultaneously measured TSBAb activities with FRTL-5 cells and with hTSHR-CHO cells in 49 patients with primary myxedema, compared them with their thyrotropin binding inhibitor immunoglobulin (TBII) activities. RESULTS: 1) hTSHR-CHO cells specifically bound bTSH and were stimulated by bTSH in terms of cyclic AMP generation in a dose dependent manner. 2) Myxedema IgG suppressed TSH-stimulated cAMP production of hTSHR-CHO cells in a dose dependent manner reaching plateau at the concentration of I g/L. Normal pooled IgG has no suppressive action at the concentration of less than 1 g/L, but caused significant suppression at the concentration of greater than 1g/L. 3) TSBAb activities measured by hTSHR-CHO cells in 49 patients with primary myxedema were as follows: Four of 25 TBII-negative cases (16%) and 22 of 24 TBII-positive cases (92%) had TSBAb activities. Most of TSBAb positive patients (95%), especially in TBII positive cases, showed very high activities of more than 90%. 4) TSBAb activities measured by hTSHR-CHO cells and those by FRTL-5 cells were both positive in 24 patients (49%), both negative in 18 patients (37%), and were discrepant in 7 patients (14%). The TSBAb activities measured with hTSHR-CHO cells and those measured with FRTL-5 cells were significantly correlated (r=0.71, p< 0.01). 5) Forty five percent of patients with primary myxedema had all of 3 kinds of activities (TBII, hTSHR-CHO cell TSBAb, FRTL-5 cell TSBAb), 37% of them had none of 3 activities and 18% of them had 1 or 2 kinds of activities only. CONCLUSION: The usefulness of hTSHR-CHO cells in measurements of TSBAb activities were confirmed. The TSBAb activities of most patients with primary myxedema measured by hTSHR-CHO cells were concordant with those measured by FRTL-5 cells. However, a small subset of patients (18%) had discrepant results in assays of TSH receptor antibodies according to the differences in TSH receptors (rat, human and porcine) used in assay. Such discrepancy may be explained by heterogeneity in epitopes for blocking TSH receptor antibodies.

Clinical Significance and Immunological Characteristics of Blocking TSH Receptor Antibodies in Patients with Hashimoto's Thyroiditis.: Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park; J Korean Endocr Soc. 1997;12(1):33-44. Published online January 1, 2001

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Abstract PDF: BACKGROUND
TSH receptor blocking antibody (TRBAb) is a pathogenic factor in the vast majority of patients with primary myxedema. It has been reported that TRBAbs are found in some patients with chronic goitrous autoimmune thyroiditis (Hashimoto's thyroiditis), but the significance or the role of TRBAb in Hashimotos thyroiditis is not clear, We recently reported that hTSHR-CHO cells which express the functional human TSH receptors are more sensitive and are better in detecting functional TSH receptor antibodies in Graves patients than FRTL-5 cells. We are to investigate the biological role of TRBAb in Hashimotos thyroiditis by measuring thyroid stimulation blocking antibody (TSBAb) activities of Hashimoto's IgG's using hTSHR-CHO cells. Moreover, we are to see if there is any difference in epitope recognition between Hashimotos TRBAb and myxedema's TRBAb by measuring TSBAb activities with mutant receptor expressing cell lines, Mcl+2 and Mc 2 in those patients. METHOD: We measured TSBAb activities of IgGs from patients with primary myxedema (PM, n= 10) and those with hypothyroid (n 20) or euthyroid (n 17) Hashimoto's thyroiditis (HT) using wild type hTSHR-CHO cells (WT) and two chimeric receptor expressing cell lines, Mcl+2 and Mc2. RESULTS: TSBAb activities measured by WT were higher in hypothyroid HT than in euthyroid HT (30.0+-23.2% vs. 6.1+-28.7, p<0.05), and TSBAb-positive rate tend to be higher in the former (20%, 5/20) than in the latter (0%, 0/17, p=0.07). TRBAbs from PM (n=4) had high TBII activities and had persistent blocking activities despite of the replacement of amino acid residue 8~165 of extracellular domain of TSHR with those of rat LH/CGR (Mcl +2). However, TRBAbs from HT (n=4) had no TBII activity at all and lost blocking activities when measured with Mcl+2. CONCLUSION: TRBAbs are found in 20% of hypothyroid patients with Hashimotos thyroiditis in assay using hTSHR-CHO cells, and they seem to play a role in the development of hypothyroidism in some patients with Hashimotos thyroiditis. TRBAbs of Hashimotos thyroiditis are different in epitope recognition from TRBAbs of primary myxedema.

Randomized Controlled Trial

Suppressive Therapy with Levothyroxine in Benignn Solitary Thyroid Nodule.: Sun Ho Kim, Jin Ho Choo, Ki Chang Oh, Hyoung Churl Cho, Jang Hyeon Cho, Joong Kyu Lim, Jin Duk Huh; J Korean Endocr Soc. 1997;12(1):45-52. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Clinically apparent thyroid nodule is a very common disease in adults. Patients are often treated with thyroxine in order to reduce the size of the nodule, but the efficacy of thyroxine-suppressive therapy with thyroxine remains uncertain. We investigated the efficacy of thyroxine-suppressive therapy and the hormonal characteristics during thyroxine therapy to find out whether such measurement could be used to determine the effectiveness of this therapy in patients with benign solitary thyroid nodule proved by aspiration biopsy. METHODS: In this study, 54 patients were randomly assigned to receive L-thyroxine (Group I, n=24) or placebo (GroupII, n=30) for 1 year. High resolution ultrasonography (10MHz) was used to measure the size of the nodules at six month intervals. Thyroid hormones and thyroglobulin assay and FNA (fine needle aspiration) was done at the same time. The dose of thyroxine was 200ug/day. Patients were followed at 6 month intervals. RESULTS: The results were as follows: 1) 13 (54.1%) out of 24 Group I patients after adequate TSH suppression had a statistically significant reduction of nodule size and before-to-after nodule volume ratios were significantly different between the Group I and Group II patients. 2) In the responders among Group I patients, the before-to-after therapy ratio of the nodule volume was not related to the pretreatment nodule size, thyroid hormones and thyroglobulin levels. CONCLUSION: Thus we concluded that an adequate suppressive dose of L-thyroxine significantly altered the volume of the benign solitary thyroid nodules 12 months later.

Original Article

The Effects of Growth Hormone Tretment on Body Composition and Glucose Metabolism in Adult Hypophysectomized Rats.: Kwan Woo Lee, Hyun Chul Lee, Kap Bum Huh, Yoon Sok Chung, Deok Bae Park, Yup Kang, Hyeon Man Kim, Seoung Oh Yang; J Korean Endocr Soc. 1997;12(1):53-60. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well known that growth hormone (GH) stimulates animal growth, but studies on metabolic effects of growth hormone have recently been increasing. The purpose of this study was to clarify the effects of growth hormone treatment on body composition and glucose metabolism in hypophysectomized growth hormone-deficient rats. METHODS: The 20-week-old rnale Sprague-Dawley rats were hypophysectomized and replaced with cortisol and thyroxine for 8 weeks, then administered with recombinant human growth hormone for 2 weeks. Group 1 consisted of intact controls (n 15), while group 2 consisted of hypophysectomized controls (n 12), and group three consisted of those with GH treatment (n 13). The body weights, body composition, blood glucose levels, plasma insulin-like growth factor-I (IGF-I) levels, euglycemic hyperinsulinemic clamp test, and glycogen synthase activities in gastrocnemius muscle were measured before and after growth hormone treatment. RESULTS: Plasma IGF-I levels in GH-treated group increased to intact control group levels after 2 weeks of GH treatment. There were significant changes in body composition after the treatment (fat mass significantly decreased and lean body mass significantly increased). There were no changes in glucose metabolism in peripheral tissue after 2 weeks of GH treatment. CONCLUSION: Human GH treatment (4 IU/kg/day) in adult hypophysectomized GH-deficient rats changed the body composition, but did not alter the glucose metabolism in peripheral tissue.

Case Reports

A Case of Down's Syndrome with Graves' Disease.: Kap Bum Huh, Kyoung Ah Kim, Jae Hoon Chung, Yeun Sun Kim, Kyu Jeung Ahn, Eun Mi Koh, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Hyun Kyun Ki; J Korean Endocr Soc. 1997;12(1):61-67. Published online January 1, 2001

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Abstract PDF: Down's syndrome (trisomy 21) has been frequently associated with thyroid disease, mainly subclinical hypothyroidism (12.5-32.5%). The occurrence of Downs syndrome in conjunction with hyperthyroidism is rare (0.6-2.5%). The mechanism that Down's syndrome was frequently associated with autoimmune thyroid disease is not clear, but T cell maturation defects and overexpression of chromosome 21 products in Down's syndrome have been suggested. A 19-year-old female was transferred because of generalized weakness. She was born to a 42-year-old mother, She had been suffered from heat intolerance, weight loss, palpitation, dyspnea on exertion and neck swelling and had intermittently taken some medication since her age 9. She had mental retardation (IQ 41) and underdeveloprnent. Exophthalmos, upward-outward slant of palpabral fissures, epicanthal folds, lowset ears, and large, protruding, fissured tongue were identified. Short fifth middle phalanges, clinodactyly and small-sized interventricular septal defect were also detected. Thyroid gland was diffusely enlarged four times the normal size, firm in consistency and had a bruit. Serum T concentration was 7.8ug/dL, T2 306ng/dL, and TSH 0.01ulU/mL. She was positive for thyroid autoantibodies (antimicosomal antibody 1,867 IU/mL, antithyroglobulin antibody 106 IU/mL, and TBII 79.6%). Twenty-four hours radioactive iodine uptake was 64%. Chromosomal analysis with T cell culture stimulated by phytohemagglutinin revealed 47XX, 21 trisomy. Pituitary hormones except TSH were fully stimulated by combined pituitary stimulation. She was finally diagnosed as Down's syndrome with Graves' disease and controlled with use of methimazole.

A Case of Methimazole Induced Agranulocytosis Treated with Granulocyte Colony Stimulating Factor ( G-CSF ).: Kwan Woo Lee, Yoon Sok Chung, Hyeon Man Kim, So Yeon Choi, Min Kyung Song, Hyun Soo Kim, Hee Sun Jeon; J Korean Endocr Soc. 1997;12(1):68-74. Published online January 1, 2001

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Abstract PDF: A 31-year-old woman admitted because of fever, chilling and sore throat for 4 days. The symptom was developed after receiving methimazole 20mg per day and carteolol 10mg per day due to Graves disease during last 4 weeks. Physical examination revealed hyperemic enlarged tonsils with whitish plaque. The peripheral blood total neutrophil count was 1,400/mm3 (absolute neutrophil count, ANC 36) and a peripheral blood smear revealed rare neutrophil with lymphocytosis. On the first day of hospitalization, the patient was severely ill with ANC 0, it was decided to administer G-CSF 2ug/kg daily. On the fifth day of hospitalization, ANC in peripheral blood count was persistently zero and bone marrow aspiration and biopsy were performed, which revealed hypocellularity and myeloid hypoplasia. G-CSF given daily for 7days, it was discontinued when the ANC reached 1,539/mm3. The availability of G-CSF may help to shorten the course of agranulocytosis and to reduce its mortality rate.

A Case of Hyperparathyroidism induced from Cystic Parathyroid Adenoma.: Ki Chul Sung, Kwon Choi, Won Tae Seo, Soon Ho Kwon, Sang Jong Lee, Joo Seob Keum, Myung Sook Kim; J Korean Endocr Soc. 1997;12(1):75-80. Published online January 1, 2001

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Abstract PDF: Cystic parathyroid adenoma is one of the rare causes of hyperparathyroidism, and is usually located in neck and mediastinum. This type of adenoma tends to cause increased serum level of parathyroid hormone and alkaline phosphatase, similar serum calcium level when compared to those of solid adenoma. Thanks to current radioimmunoassay and easy accessibility to serum autoanalyzer, serum calcium level and parathyroid hormone level are more easily measured, which in turn lead to more easier diagnosis of hyperparathyroidism. Also improvement in imaging and nuclear diagnostic method of parathyroid lesion are suggested to enable easy diagnosis of cystic parathyroid adenoma. A 35-year-old male presented with easy fatigability for 12 months. The serum calcium, phosphate, alkaline phosphotase were 11.5mg/dL, 1.4mg/dL, 194IU/L respectively and his parathyroid hormone level in serum was 126.42pg/mL. Neck CT showed enlargement of right lobe of thyroid gland with well defined inhomogenously enhanced density inside the right thyroid gland. The patient was diagnosed of hyperparathyroidim due to parathyroid adenoma and was surgically removed. The surgical biopsy showed cystic parathyroid adenoma. After operation his general condition was improved and serum calcium, phosphate, parathyroid hormone level were normalizd. We report a case of hyperparathyroidism caused by cystic parathyroid adenoma with brief review of literature.

A Case of Functioning Parathyroid Cancer with Hypokalemia.: Yoon Hee Choi; J Korean Endocr Soc. 1997;12(1):81-89. Published online January 1, 2001

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Abstract PDF: The parathyroid carcinoma is rare disorder and its reported incidence is 1-2% of primary hyperparathyroidism. Parathyroid cancer shows more profound clinical symptoms and signs than adenoma or hyperplasia: more severe renal and bony complications, higher calcium levels (>15 mg/dL) and palpable neck mass. It usually diagnosed after operation when it shows malignant pathologic findings, local invasion, distant metastasis, or even recurrence. The treatment is surgical resection. Hypokalemia is relatively common feature of primary hyperparathyroidism but it should be marked because of its arrhythmogenic effect when accompanies with hypercalcemia. We experienced a hyperfunctioning parathyroid carcinoma in 53 year old rnan confirmed postoperatively which showed hypokalemia normalized after operation.

A Case of Cushing's syndrome due to Primary Pimary Pigmented Nodular Adrenal Dysplasia ( PPNAD ): A Case of Carney's Complex.: Soon Jib Yoo, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Youn Sik Kim, Jong Min Lee, Jong Man Won; J Korean Endocr Soc. 1997;12(1):90-98. Published online January 1, 2001

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Abstract PDF: Primary Pigmented Nodular Adrenal Dysplasia (PPNAD) is a rare cause of Cushing's syndrome in infants and young adults. The familial occurrence, it may be variably associated with a complex of other pathologic characteristics that manifests extraadrenal disorders (includes cardiac myxomas, lentigines, mammary myxoid lesions, testicular tumors, pituitary adenomas, and neuroectodermal tumors) was considered indicative of Carneys complex. This was based on the failure of cortisol suppression by high-dose dexamethasone, either normal or suppressed basal adrenocorticotropic hormone (ACTH) levels, and normal radiographic studies of the sellar turcica, and adrenals glands is almost normal or slightlg eulaged.. Bilateral adrenalectomy has thus the only effective means of cure. The disease may be a component of a rare, but potentially dangerous complex of abnormalities that follow an autosomal-dominant mode of inheritance. Recently we experienced a case of Carney's complex composed by Cushings syndrome due to PPNAD with familial purple colored lentigines on their lips and report it with reviews of the literatures.

A Case of Pheochromocytoma associated with Ectopic ACTH Syndrome.: Young Sun Hong, Hee Jin Kim, Yeon Ah Sung, Nan Ho Kyung, Ho Jung Kim, Sung Sook Kim; J Korean Endocr Soc. 1997;12(1):99-104. Published online January 1, 2001

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Abstract PDF: The syndrome of ectopic production of ACTH by non-pituitary neoplasm occur with various types of tu#rnors. Pheochromocytoma is a rare, but one of the important causes of this syndrome. Recently we experienced a 36-year-old male patient with ACTH-producing pheochromocytoma. After left adrenalectomy, serum ACTH level retumed to the normal range. The patient became normotensive without antihypertensive agents and hyperglycemia resolved and insulin therapy was discontinued. Secretion of ACTH was confirmed by immunohistochemical stain.

Original Article

Adrenal Myelolipoma Confirmed by Fine Aspiration Biopsy.: Young Sik Jung, Jun Ho Whang, Jeon Ho Yang, Hyeon Soo Shin, Ih Geun Kim, Ki Sung Ahn, Sung Gug Chang, Sang Chae Lee, Jung Dong Bae, Ho Sang Shon, Mi Ok Park, Jae Bok Park, Yeong Hwan Lee; J Korean Endocr Soc. 1997;12(1):105-110. Published online January 1, 2001

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Abstract PDF: Adrenal myelolipomas are rare, benign tumors cornposed of mature fat and bone marrow elements. Most are small, asymptomatic tumors found incidentally at postmortem examination, Fine needle aspiration biopsy can be used to confirm the diagnosis and avoid an unnecessary operation. We report a case of adrenal myelolipoma confirmed by fine needle aspiration biopsy. A 77-year-old woman with complaining of upper abdominal pain for 2 days was found to have an adrenal mass. She took dexamethasone frequently for 3 years due to multiple arthralgia. Ultrasono-graphy showed a 6cm-sized, suprarenal mass and a stone in the gall bladder with thickened wall. Computed tomography and magnetic resonance imaging scan also presented a suprarenal mass. Endocrinologic results were within normal limits. Adrenal myelolipoma was confirmed by computed tomography-guided fine needle aspiration biopsy without surgery.

Case Report

A Case of Multiple Endocrine Neoplasia Type 1.: Soon Jib Yoo, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Jong Man Won, Young Seok Cho, Yong Jik Sung, Kyung Sub Song, Jin Young Yoo, Chul Woo Lee; J Korean Endocr Soc. 1997;12(1):111-119. Published online January 1, 2001

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Abstract PDF: Multiple endocrine neoplasia type 1 (MEN 1) is the association of neoplastic transformation of parathyroid, pituitary, and pancreatic islet cells. This syndrome is inherited as an autosomal dominant trait. A 38-year-old woman presented with general weakness and mental changes. She had experienced same symptoms 7 years ago, after then her weight gradually increased. Insulinoma was suspected by markedly decreased blood glucose level (20mg/dL) and the increased insulin/glucose ratio (0.43) that sampled in emergency room at the time of mental change. Unusually large pancreatic tail mass and Lt, adrenal gland mass were detected by abdominal CT. Percutaneous transhepatic portal vein catheterization with insulin sampling showed sudden step up of insulin/glucose ratio at the middle portion of pancreas. Measuring of basal pituitary hormones as a screening procedure of MEN showed increased basal prolactin level. Combined pituitary stimulation test showed blunted response of prolactin to TRH and sellar magnetic resonance imaging showed intrasellar mass. Thyroid nodule was palpated on her anterior neck. Thyroid scintigram showed cold nodule, and there was no lymphadenopathy around the nodule by the thyroid sonogram. Fine needle aspiration cytology showed benign hyperplastic follicular cells only. Serum ionized calcium and parathyroid hormone level were normal. Under the impression of MEN type I, the distal pancreatectomy, splenectomy, Lt. thyroid lobectomy and Lt. adrenalectomy was performed at the same time. Histologic examination of the surgically removed tissues revealed pancreas islet cell tumor, adrenal cortical adenoma and thyroid adenoma. Transient hyperglycemia was developed after surgical intervention, but thereafter she never felt any symptoms of hypoglycemia till now and her blood glucose showed completely normal level with oral glucose tolerance tests. We present this case with a review of literature.

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