Endocrinology and Metabolism

Original Articles

Miscellaneous
Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea: Hoon Sung Choi, Jin Taek Kim, Hong Kyu Lee, Wook Ha Park, Youngmi Kim Pak, Sung Woo Lee; Endocrinol Metab. 2021;36(6):1298-1306. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1226

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Background
Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels.
Methods
We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays.
Results
During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function.
Conclusion
Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

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An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data
Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
International Journal of Environmental Research and Public Health.2022; 19(10): 5800. CrossRef

Clinical Study
High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly: Youngmi Kim Pak, Hoon Sung Choi, Wook Ha Park, Suyeol Im, P. Monica Lind, Lars Lind, Hong Kyu Lee; Endocrinol Metab. 2021;36(2):436-446. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2020.883

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Abstract PDF Supplementary Material PubReader ePub

Background
High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time.
Methods
Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up.
Results
AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose.
Conclusion
These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Citations

Citations to this article as recorded by

An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data
Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
International Journal of Environmental Research and Public Health.2022; 19(10): 5800. CrossRef
A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice
Sora Kang, Aden Geonhee Lee, Suyeol Im, Seung Jun Oh, Hye Ji Yoon, Jeong Ho Park, Youngmi Kim Pak
International Journal of Molecular Sciences.2022; 23(23): 14871. CrossRef

The Localization of Microadenoma with Sella Imaging Study and Inferior Petrosal Sinus Sampling in Cushing's Disease.: Jae Seok Jeon, Sang Jeon Choi, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hee Won Jung, Dae Hee Han, Moon Hee Han, Kee Hyun Chang; J Korean Endocr Soc. 1996;11(4):492-499. Published online November 7, 2019

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Abstract PDF: Background
Inferior petrosal sinus sampling(IPSS) is known to be useful for the differential diagnosis of ACTH-dependent Cushings syndrome and for the preoperative lateralization of pituitary microadenoma. We tried to analyze the relative value of IPSS in localization of microadenoma as compared with sella imaging study including computerized tomogram(CT) or magnet resonance imaging(MRI) in Cushings disease. Methods: We reviewed the clinical records of 21 patients with Cushings disease who underwent IPSS and the radiologic study such as sella CT or sella MRI preoperatively followed by transsphenoidal microsurgery. By pathologic examination including immunohistochemistry and postoperative clinical and biochemical evaluation we confirmed the diagnosis of Cushings disease due to pituitary microadenoma in all 21 cases. Results: Sella CT or sella MRI detected microadenoma in 57.1% of cases( =12/21), while recently available dynamic MRI did so in 7 out of S cases. With IPSS the diagnosis of Cushings disease was possible in 90.5% of cases(= 19/21), but accurate lateralization of microadenoma was achieved in only 63.2% of cases( =12/19). IPSS precisely localized the pituitary microadenoma in 6 out of 9 cases whose lesion were not detected by the radiologic study. Of 7 cases in which IPSS failed to localize microadenoma, the radiologic study detected the lesion in 6 cases. Of 5 cases in which IPSS and the radiologic study showed a discrepancy in location of microadenoma, the radiologic study correctly localizaed the lesion in 4 cases and IPSS did so in one case. Conclusion: IPSS is not more reliable than sella imaging study for preoperative localization of microadenoma in Cushings disease. However it might have a complementary role, especially when sella imaging study failed to visualize the lesion.

The Incidence of Thyroid Autoantibody in Subacute Thyroiditis and the Clinical Characteristics of Greeping Thyroiditis.: Jae Seok Jeon, Won Bae Kim, Hae Young Park, Young Joo Park, Hyun Kyung Chung, Sang Jeon Choi, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh; J Korean Endocr Soc. 1996;11(4):438-446. Published online November 7, 2019

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Abstract PDF: Background
Subacute thyroiditis is a spontaneously resolving inflammatory disorder of thyroid gland, usually associated with painful goiter and short-lived thyrotoxicosis. Although its etiology is yet to be established, much evidence suggests viral infections and genetic factors play important roles. Usually, both lobes of thyroid gland are involved simultaneously, but in some patients one lobe is involved first and the other later(creeping thyroiditis), Thyroid autoantibodies which might appear probably due to inflammatory release of thyroid antigens, are found in a variable number of patients with subacute thyroiditis. However there have been few detailed reports on their incidence in Korean patients with subacute thyroiditis. So, we were to see the elinical characteristics of patients with subacute thyroiditis with special regards to the incidence of thyroid autoantibodies and to the incidence and characteristics of creeping thyroiditis, Methods: We reviewed the clinical records of 85 patients with subacute thyroiditis(7 men and 78 wornen, meam age of 43+9 years) who had visited the thyroid clinic in Seoul National University Hospital between 1986 and 1994. Results: At initial visit, the incidenees of thyroid autoantibodies were as follows: anti- microsomal antibody 7.8%, anti-thyroglobulin antibody 22.1%, and thyratropin binding inhibitor inununglobulin 6.3%. During the follow-up period, thyroid autoantibodies appeared most frequently between the first and the second month after initial visit. Compared to those with non-creeping thyroiditis, the patients with creeping thyroiditis(21.4%) had nonspecific systemic sy~rnptoms more frequently(89% vs. 42%, p<0.05). They required steroid therapy more ftequently(89% vs. 52%, p <0.05), and needed longer duration of treatment(9.3+6.2weeks vs, 4.7+3.7weeks, p<0.05). The incidence of abnormalities in liver function and the incidence of thyroid autoantibodies were higher in non-creeping thyroiditis group. Conclusion: In accordance with previous reports, thyroid autoantibodies were detected in only a small portion of Korean patients with subacute thyroiditis. Rather different clinical manifestations and different incidences of thyroid autoantibodies between ereeping group and non-creeping group suggest differences in the pathogenetic mechanisms between those two groups. However, there is need for further study to validate such observation and to elucidate the mechanisms.

A Study on the Urinary Iodine Excretion in Normal subjects and Patients with Thyroid disease.: Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Seok In Lee, Woon Bae Kim, Hye Young Park, Chang Soon Koh; J Korean Endocr Soc. 1995;10(4):386-394. Published online November 7, 2019

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Abstract PDF: An adequate supply of dietary iodine is essential for the synthesis of the thyroid hormons. The measurement of dietary iodine intake is important for the clinical assessment of thyroid disease, especially in areas where iodine intake is excessive or deficient.To evaluate dietary iodine intake in Korean and its effects on thyroid function, we measured urinary iodine excretion with morning urine by electrode method in 184 normal subjects, 96 postpartum women and 181 patients with thyroid disease from October 1994 to February 1995. The results were as follows;1) In normal control, the mean value of urinary iodine excretion was 3.8+-2.7mg/L (range 0.1-15.0mg/L). However, there was no sex and age differences in the urinary iodine excretion.2) In postpartum women, the urinary iodine excretion was 9.0+-10.8mg/L who were not taken high iodine diet(Miyok-Guk), the mean value was statistically higher than normal control(p<0.01) and significant increased the urinary iodine excretion after eating of high iodine diet(p<0.01).3) In volunteer, there were increase of urinary iodine excretion more than 10 folds after high iodine diet and medication.4) The urinary iodine excretion in patients with thyroid diseases was not different from normal control, and there were no significant differences of urinary iodine excretion among the patient groups. The urinary iodine excretion in the acute stage of patients with subactue thyroiditis or painless thyroiditis was significantly increased compared to the recovery stage. However, it was not significantly different from that of normal control.In conclusion, urinary iodine excretion in Korean population is very high comparing to the reported data in Western population but similar with Japanese. The urinary iodine excretion is significant increase( more than 10-folds of basal level) after high iodine diet or high iodine containing medication in postpartum women or healthy persons. As a clue of destruction induced thyrotoxicosis, the urinary iodine excretion measurement is not valid in area where iodine intake is excessive like Korea.

Assay of Thyrotropin Receptor Antibodies with Recombinant Human Thyrotropin Receptor Expressed on Chinese Hamster Ovary Cells.: Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Jae Hoon Chung, Ka Hee Yi, Kyung Soo Ko, Won Bae Kim; J Korean Endocr Soc. 1995;10(4):347-361. Published online November 7, 2019

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Abstract PDF: Thyroid stimulating antibody which results in the development of hyperthyroidism and goiter in Graves' patients used to be measured by using rat thyroid cells, FRTL-5. However, this assay has disadvantages: decreased sensitivity due to differences in species, and fastidious culture conditions for FRTL-5 cells. Thus, we recently created stably transfected Chinese hamster ovary(CHO) cells containing the human TSH receptor(hTSHR-CHO) and developed optimal conditions for the measurement of thyroid stimulating antibody using hTSHR-CHO cells. In this study, to evaluate the clinical relevance of thyroid stimulating antibody measurement using hTSHR-CHO cells, we measured thyroid stimulating antibody activities of IgGs from Graves' disease and other thyroid disease using hTSHR-CHO cells, and compared to those of thyroid stimulating antibody assays using FRTL-5 cells. 1) The cut off value of positive thyroid stimulating antibody activity measured in hTSHR-CHO cells was 145%(above the mean +2SD) which was lower than 165% in FRTL-5 cells. The intra-assay and inter-assay variances were 3.9% to 9.0% and 12.7% to 1.6%, respectively. 2) Thyroid stimulating antibody activity was detected in 90% of patients with untreated Graves' disease when patients initially presented. Further, in patients seen initially but already under therapy, 75% had positive values if they were hyperthyroid but only 43% had IgGs with activity if they were euthyroid. Patients in clinical remission after therapy showed positive values in 23% of cases. Only 2 of 25 patients with Hashimoto's thyroiditis showed weak thyroid stimulating antibody activity, none of 18 patients with nodular nontoxie goiter, 1 of 15 patients with primary myxedema, and 2 of 33 control patients with no thyroid disease. Thus, the detection frequency and specificity of the assay with hTSHR-CHO cells was excellent for this type bioassay.3) The detection frequency of thyroid stimulating antibody activity by hTSHR-CHO cells assay system(90%) was higher than that by FRTL-5 cells assay system(66%) in untreated Graves' patients. Those two activities were positively correlated with each other(r=0.52, p<0.001). However, some IgGs showed discrepancy of the thyroid stimulating antibody activity measured in hTSHR-CHO cells and in FRTL-5 cells; 56 of 87 patients were positive in both cells system, 8 of 87 were negative in both cells system, 1 of 87 was only positive in FRTL-5 cells and 22 of 87 were only positive in hTSHR-CHO cell system. Thus, 73%(22/30) of IgGs showing negative values of thyroid stimulating antibody activities in FRTL-5 cells were detected its activities in hTSHR-CHO cells system.In summary, thyroid stimulating antibody assay with hTSHR-CHO cells exhibited so excellent sensitivity and specificity that this technique should be used for clinical practice as well as basic research.

Thyroid Stimulating Antibody Assay with Chinese Hamster Ovary Cells Expressing Human Thyroid Stimulating Hormone (TSH) Receptor; Optimization of Assay Condition.: Bo Youn Cho, Hong Kyu Lee, Young Kee Shong, Chang Soon Koh, Ka Hee Yi, Yeon Sahng Oh, Won Bae Kim; J Korean Endocr Soc. 1995;10(4):333-346. Published online November 7, 2019

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Abstract PDF: We investigated the optimal condition of thyroid stimulating antibody(TSAb) assay using Chinese hamster ovary cells transfected with cDNA of human TSH receptor(TSHr-CHO) stably expressing functional TSH receptors. The extracellular cAMP responses of TSHr-CHO cells to the stimulation of bTSH or Graves' IgG were observed in three different incubation media. Stimulation indices of extracellular cAMP were higher when sucrose containing NaCl-free isotonic Hank's balanced salt solution(HBSS)(media A)was used as incubation media than those of NaCl-free hypotonic HBSS(media B) or those of NaCl containing isotonic HBSS(media C). The incubation of TSHr-CHO cells in media B caused marked increase in the basal cAMP level without concomittant fold-increase in the stimulated cAMP level at various doses of bTSH and Graves' IgG. Decreasing the stimulation indices of extracellular cAMP, use of media B failed to detect TSAb activities in two TSAb-positive Graves' IgG tested. In case of media C, extracellular cAMP responses are poor at 0.001 and 0.1U/L of bTSH and at all doses of Graves' IgG tested(0.5, 1, 5g/L). The incubation of TSHr-CHO cells in media B caused significant increase in the number of trypan blue-stained, nonviable cells(5.7+-1.5, 7.6+-1.9 and 8.5+-1.6% at 1, 2 and 3h of incubation, respectively; p<0.01) comparing to those incubated in media A or media C(about 2-3% in both media). Those decrease in the viability of TSHr-CHO cells when incubated in hypotonic incubation media may explain the decrease in the stimulation index of extracellular cAMP with the use of media B in contrast to the case of FRTL-5 cells. TSAb assay of 87 consecutive fresh Graves' patients with TSHr-CHO cells using media A detected TSAb activities in 90%(78 patients) of them, and moreover TSAb activities showed significant positive correlation with the pre-treatment serum T_3 and free T_4 levels of those patients. We conclude that TSAb assay with TSHr-CHO cells is a sensitive and physiologically relevant assay system to measure TSAb activities merely through measurements of extracellular cAMP provided that the cells are incubated in NaCl-free isotonic incubation media.

Relationship between Blood Pressure and Insulin Level or Red Cell Membrane Na+ Transport in Acromegaly.: Seong Yeon Kim, Hyun Kyu Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh; J Korean Endocr Soc. 1995;10(1):35-44. Published online November 6, 2019

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Abstract PDF: To test the hypothesis that hyperinsulinemia and/or abnormalities of red cell membrane Na^+ transport are concerned in the pathogenesis of hypertension, we investigated the relationship between blood pressure, insulin level and red cell membrane Na^+ transport in patients with acromegaly which is frequently associated with hypertension, hyperinsulinemia and abnormalities of red cell membrane Na^+ transport.The results were as follows;1) BMI and both systolic and diastolic blood pressure were significantly higher in patients with acromegaly than in control subjects.2) Fasting glucose and insulin levels were higher, and both serum glucose and insulin responses after a 75g glucose load were significantly increased in patients with acromegaly as compared with control subjects.3) Vmax of Na^+-Li^+ countertransport were significantly higher in patients with acromegaly than in control subjects while red cell Na^+ concentration and Vmax of Na^+, K^+ ATPase were similar in the two groups.4) In multiple stepwise regression analysis, age was directly correlated with both systolic and diastolic blood pressure in acromegaly. On the other hand both insulin level and red cell membrane Na^+ transport showed little correlation with either systolic or diastolic pressure. 5) Prevalence of hypertension in acromegaly was 39%(9 out of 23) and only age except for blood pressure was significantly higher in hypertensive acromegalic patients than in normotensive acromegalic patients while GH level, insulin levels and red cell membrane Na^+ transport were similar in the two groupsThese results suggest that hyperinsulinemia or abnormalities of red cell membrane Na^+ transport are not causally related to hypertension in patients with acromegaly.

Case Report

A Case of Thyroid Anaplastic Cancer with Intestinal Metastasis.: Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Jae Seok Jeon, Min Seon Kim, Won Bae Kim; J Korean Endocr Soc. 1994;9(4):375-379. Published online November 6, 2019

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Abstract PDF: Thyroid anaplastic cancer is one of the most malignant neoplasms encountered in human. These tumors usually present as rapidly enlarging neck mass in old patients who may or may not have had a previously recognized goiter. The distant metastases of anaplastic cancer eventually occur in about 50% patients, mostly in the lung and bone and are an important prognostic factor, substantially reducing survival time.A 66-year old man visited out hospital because of rapidly growing anterior neck mass and hoarseness. He was diagnosed as thyroid anaplastic cancer with lymph node and lung metastasis and received combined chemotherapy and radiation therapy. On the 8th hospital day, severe abdominal pain developed and exploratory laparotomy was conducted. During operation, two intestinal mass were discovered, one of which was perforated. The microscopic examinations showed that undifferentiated malignant cells were infiltrated in the wall of small bowel. We report this case because we first experienced thyroid anaplastic cancer with intestinal metastasis.

Original Articles

Insulin Resistance, Body Fat Distribution, and Sex Hormones in Healthy Men and Premenopausal Women.: Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chan Soo Shin, Chang Soon Koh, Tae Geun Oh, Woon Bae Kim; J Korean Endocr Soc. 1994;9(4):366-374. Published online November 6, 2019

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Abstract PDF: It is well known that obesity central obesity is associated with insulin resistance and some studies reported that sex hormones were associated with insulin resistance. Recently, low levels of sex-hormone binding globulin(SHBG), an indirect index of androgenicity, have been observed to predict the development of non-insulin dependent diabetes mellitus(NIDDM) in women and SHBG has been proposed as a marker for insulin resistance. In contrast to findings in women, decreased SHBG did not predict the occurrence of NIDDM in men, so it is suggested that sex hormones may have a different role for insulin resistance between men and women. To investigate the difference of the associations among the body fat distribution, sex hormone and insulin sensitivity index in men and women, we measured body-mass index(BMI) and waist to hip circumference ratio(WHR) and concentrations serum SHBG, total testosterone, free testosterone, and dehydroepiandrosterone sulfate(DHEA-S) concentrations in 29 healthy adults(men:19, women:10) who showed normal glucose tolerance. Insulin sensitivity index(M/I) was measured by euglycemic hyperinsulinemic clamp. There were no differences in age, BMI, fasting plasma glucose, insulin and free fatty acid levels between men and women. WHR of men is higher than that of women(0.82+-0.01 vs. 0.73+-0.01, p=0.002). Insulin sensitivity index(M/I) is similar in men and women(7.80+-0.71 mg/kg/min/uU/ml X 100 vs. 9.74+-0.89 mg/kg/min/uU/ml X 100, p=0.196).In Pearson's correlation, M/I was significantly correlated with BMI(r=-0.69, p<0.01) and WHR(r=-0.68, p<0.01) in men and DHEA-S(r=-0.68, p<0.05) and SHBG(r=0.61, p=0.056) concentrations in women.In multiple regression analysis, M/I had the most significant association with BMI(R^2=0.484, beta=-0.696, p<0.001) in men and DHEA-S(R^2=0.471, beta=-0.686, p<0.05) concentration in women.Conclusively, we found that sex hormones were significantly associated with insulin resistance and the effects of sex hormones on insulin resistance may be different in men and women.

Effect of Antiliyolytic Agents on Glueose Metabolism in Thyrotoxic Patients.: Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chan Soo Shin, Chang Soon Koh, Hun Ki Min, Tae Geun Oh, Chul Hee Kim, Moon Kyu Lee, Jong Ho Ahn, Kee Up Lee; J Korean Endocr Soc. 1994;9(4):325-331. Published online November 6, 2019

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Abstract PDF: Decreased glucose tolerance is often found in patients with thyrotoxicosis but the pathogenetic mechanisms are poorly understood. Since the concentrations of free fatty acid are usually elevated due to increased lipolysis in thyrotoxicosis, the preferential oxidation of the free fatty acids may explain the decreased glucose tolerance in hyperthyroidism. The aim of this study was to investigate whether lowering plasma free fatty acid(FFA) by acipimox, a long-acting antilipolytic agent, could affect glucose metabolism in thyrotoxicosis. We performed intravenous glucose tolerance test with acipimox or placebo in 6 untreated thyrotoxicmen and 6 age-and body mass index(BMI)-matched controls. The following results were obtained.1) The basal plasma FFA concentration in thyrotoxic patients were significantly higher than those in controls(997.0+-303.4 uEq/L vs. 290.5+-169.1 uEq/L; p<0.01). 2) Plasma FFA concentrations decreased rapidly with acipimox ingestion in both controls and thyrotoxic patients.3) Plasma glucose concentrations were significantly lower with acipimox ingestion than with placebo in thyrotoxic patients from 17min after intravenous glucose load and to the end of the study.4) Plasma insulin concentrations in thyrotoxic patients with acipimox ingestion were higher at 5, 7 min after iv glucose load.5) In thyrotoxic patients, glucose disappearance rate(K_glucose) in acipimox treatment was significantly higher than that in placebo treatment(2.44+-0.84 vs. 1.58+-0.37;p<0.05). 6) K_glucose values were inversely correlated with basal FFA concentrations(r=-0.58, p<0.05). In summary, in thyrotoxic patients with elevated plasma FFA levels, acipimox lowered plasma FFA, which in turn improved glucose tolerance.

Changes in Thyrotropin Receptor Blocking Antibody after Antithyroid drug Administration to Patients with Atrophic Autoimmune Thyroiditis (Primary Myxedema).: Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Jae Hoon Chung, Chang Soon Koh, Chan Soo Shin, Won Bae Kim; J Korean Endocr Soc. 1994;10(3):229-241. Published online November 6, 2019

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Abstract PDF: It is well Known that antithyroid drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels including thyroid stimulating antibodies(TSAb) in most patients suggesting the immunosuppressive or immunomodulating effects of antithyroid drugs. In the context of view that thyrotropin receptor blocking antibody may play an important pathogenetic role at least in some patients with primary myxedema(chronic atrophic autoimmune thyroiditis), antithyroid drug treatment in these patients might be beneficial to disease course. To evaluate the effect of antithyroid drug on the thyrotropin receptor blocking antibody levels, we serially measured thyrotropin-binding inhibitor immunoglobulins(TBII) and thyroid stimulation blocking antibodies(TSBAb) using FRTL-5 cells, antimicrosomal- and antithyroglobulin antibody activities in 7 patients with primary myedema who have blocking TSH receptor antibodies during 6 months of methimazole(MMI, 40mg/day) administration. TBII and TSBAb activities did not change after MMI, but one of them showed stepwise decrease and disappearance of TBII and TSBAb activities. Antimicrosomal- and antithyroglobulin antibody activities decreased significantly after 3 months of MMI administration in those patients. These results suggest a minimal effect of antithyroid drug treatment on the level of thyrotropin receptor blocking antibodies. Persistence of thyrotropin receptor blocking antibodies despite of the decrease in antimicrosomal and antithyroglobulin antibodies might suggest that blocking TSH receptor antibodies of primary myxedema is produced mainly in extrathyroidal tissue in contrast to the thyroid stimulating antibodies of Graves' disease. One patient, whose blocking antibody have disappeared after MMI treatment, is under observation to see if she will remain in remission of hypothyroidism.

Case Report

A Case of Thyrotropin - Secreting Pituitary Adenoma.: Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Woon Bae Kim, Hye Young Park, Jin Sung Kim; J Korean Endocr Soc. 1994;10(2):153-160. Published online November 6, 2019

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Abstract PDF: thyrotropin-secreting(TSH) pituitary adenoma is extremely rare condition causing hyperthyroidism by uncontrolled secretion of thyrotropin. Among total pituitary adenomas, less than 1 percent are thyrotropin-secreting type, and only about 150 cases have been reported till now. However, increasing numbers of cases are being found due to the availability of ultra-sensitive TSH assay. We report here a patient with thyrotropin-secreting pituitay adenoma secreting TSH with production of lutenizing hormone(LH), follicle stimulating hormone(FSH), growth hormone(GH), prolactin(PRL) and free alpha-subunit.A 21-years old man visited thyroid clinic because of palpitation and dyspnea on exertion. He had diffuse goiter and features of mild thyrotoxicosis, and his thyroid function test showed increased T3, T4 and normal TSH. Serum free alpha-subunit concentration was 7420.5pg/ml(24.7mIU/ml) and the molar ratio of free alpha-subunit to TSH was 15.9. Basal pituitary hormone levels except TSH and the response to combined pituitary stimulation test were normal. A large sellar mass extending into frontal lobe was found on sellar MRI, so it was removed surgically leaving residual tumor mass due to the extensive nature of tumor. In immunohistochemical study the tumor tissue was stained with antibodies to TSH, LH, FSH, GH and PRL. His hyperthyroidism and goiter disappeared after partial removal of tumor. Somatostatin analogue(octreotide acetate) were given continuously via subcutaneous route(150 ug/day) using infusion pump to reduce the size of residual tumor. After 4 months of octreotide infusion, the size of tumor decreased slightly, and he is under treatment without any side effect.

Original Articles

Evaluation of the Usefulness of Free T4 Measured by 2 - Step Iimmunoextraction in the Patients with Thyroid and Non - Thyroid Diseases.: Bo Youn Cho, Hong Kyu Lee, Jae Hoon Chung, Seok In Lee, Won Bae Kim, Chang Soon Koh; J Korean Endocr Soc. 1994;10(2):98-104. Published online November 6, 2019

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Abstract PDF: Many methods and commercial kits have become available for directly measuring free thyroxine(free T_4). However, most of them are inadequate for routine laboratory use because of their complexity and inaccuracy. Recently, 2-step RIA methods by immunoextraction(2-step immunoextraction) for free T_4 have been developed to improve its accuracy and convenience. We evaluated the usefulness of free T_4 measured by 2-step immunoextraction compared to free T_4 index(FT_4I), free T_4 measured by 1-step RIA, and TSH in 204 patients with thyroid and non-thyroid disease. There were no differences in sensitivities and specificities of free T_4(1-step, 2-step), FT_4I and TSH in the patients with hyperthyroidism and euthyroid nodule. However, the sensitivity of TSH in hypothyroidism was remarkablely higher than the others(100.0% vs. 61.5-81.5%). The sensitivity of free T_4(2-step) was also higher than those of free T_4(1-step), FT_4I and TSH in the patients with non-thyroid disease(94.3% vs. 74.3-83.8%). The values of free T_4 measured by 1-step RIA were significantly lower than those by 2-step immunoextraction, especially in the patients with non-thyroid disease(1.10+-0.04 vs. 1.55+-0.03ng/dL, p<0.05).In conclusion, no significant differences were found in sensitivity and specificity of free T_4(1-step, 2-step), FT_4I, and TSH in the patients with thyroid diseases except in hypothyroidism. However, the sensitivity of free T_4 measured by 2-step immunoextraction was significantly higher than the other tests, especially in the patients with non-thyroid disease. Therefore, free T_4 assay using 2-step immunoextraction is useful to differentiate the non-thyroid disease from thyroid diseases.

A Clinical study on the diagnesis and Treatment of Cushing's Disease - The significance of bilateral inferior petrosal sinus sampling -.: Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Jae Seok Jeon, Hyeong Kyu Park, Chang Soon Koh, Hun Ki Min, Heu Won Jeong, Dae Hee Han, Moon Hee Han, Kee Hyun Jang; J Korean Endocr Soc. 1994;9(2):115-120. Published online November 6, 2019

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Abstract PDF: Bilateral inferior petrosal sinus sampling(IPSS) is known to be useful for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative localization of pituitary microadenomas.To evaluate the usefulness of IPSS, we performed the procedure in the 17 cases of ACTH-dependent Cushing's syndrome including 2 cases of macroadenomas, 6 of them with CRH stimulation test. A inferior petrosal sinus-to-peripheral ACTH ratio of 2:1 or greater(3:1 after CRH stimulation) indicates a pituitary source of ACTH hypersecretion, and a ratio of the ACTH level in one inferior petrosal sinus to the ACTH level in the other of 1:4 or greater lateralizes the microadenomas to that half of the pituitary gland.With these criteria, we diagnosed Cushing's disease in 15 of 17 cases of ACTH-dependent Cushing's syndrome, and localized the lesion in 8 of 13 cases of microadenoma.In conclusion, IPSS with CRH stimulation has high diagnostic accuracy in the differential diagnosis of ACTH-dependent Cushing's syndrome, but still has the limitations on the localization of microadenoma.

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