Endocrinology and Metabolism

Volume 10(4); December 1995

Review Article

Prognosis and Treatment of Differentiated Thyroid Cancer.: Bo Youn Cho; J Korean Endocr Soc. 1995;10(4):313-328. Published online November 7, 2019

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Abstract PDF: No abstract available.

Editorial

Measurement of Thyrotropin Receptor Antibody.: Young Kee Shong; J Korean Endocr Soc. 1995;10(4):329-332. Published online November 7, 2019

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Abstract PDF: No abstract available.

Original Articles

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.

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.

Clinical and Endocrinologic Differences between Prolactinoma and Pseudoprolactinoma Proven by Immunohistochemical Study.: Jae Wha Jo, Eun Jig Lee, Moon Suk Nam, Su Youn Nam, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Tae Seung Kim, Sun Ho Kim, Kyung Rae Kim, Bong Soo Cha, Ji Hyun Lee, Sung Kil Lim; J Korean Endocr Soc. 1995;10(4):362-369. Published online November 7, 2019

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Abstract PDF: Hyperprolactinemia is the most common hypothalamo-pituitary disorder encountered in clinical endocrinology. Excluding the drug-induced hyperprolactinemia, the most common cause of this disorder is a pituitary tumor. Prolactinoma is mainly made up of prolactin-secreting cells but pseudoprolactinoma is tumor that does not secrete prolactin itself. The pseudoprolactinoma interrupts the flow of prolactin inhibiting factor, dopamine, from the hypothalamus through the pituitary stalk to the normal pituitary. The differentiation prolactinoma from pseudoprolactinoma is vitally important since true prolactinomas are most commonly responded well in terms of tumor shrinkage to medical treatment using dopamine agonist therapy, whereas pseudoprolactinomas do not. Thus surgical treatment is clearly indicated as first-line treatment if we know that a lesion is a pseudoprolactinoma. We compared prolactinoma with pseudoprolactinoma in clinical and endocrinologic characteristics of 48 cases after immunohistochemical diagnosis. We could not find any differential point of both tumors in clinical and radiological characteristics although some differences were exist. But we had found the relationship between the mean level of pretreatment serum prolactin and the presence of positive immunohistochemical stain for prolactin. The pretreatment serum prolactin level was significantly higher in patients with tumors showing many prolactin immunohistochemical staining cells than in those with none(p<0.05). When the pretreatment serum prolactin exceeded 100ng/ml, the tumors contain 94% of prolactin positive cells in stain. So, if the pretreatment serum prolactin exceeds 100ng/ml, we primarily suspect prolactinoma and medical treatment should be considered. If the pretreatment level below 100ng/ml, we suspect pseudoprolactinoma and surgical treatment should be considered.

Correlation between Urinary Growth Hormone Level and Peak Serum Growth Hormone Level in Growth Hormone Provocation Test Using Insulin and L - dopa.: Woo Yeong Chung, Byung Kiu Park, Chul Ho Kim; J Korean Endocr Soc. 1995;10(4):370-376. Published online November 7, 2019

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Abstract PDF: To investigate the correlation between urinary growth hormone(GH) level and peak serum GH level, urinary GH value measured by overnight collection of urine for 10 hours and serum GH value in response to GH provocation test using insulin and L-dopa were measured in 9 cases of GH complete deficiency(GCD), 19 cases of GH partial deficiency(GPD) and 40 cases of GH normal short stature(GHN). Urinary GH values were measured by the EIA method using PICOIA HGH plate(Joo Woo Pharmaceutical Co., Japan). Urinary GH was expressed in terms of nanograms per gm creatinine(ng/gCr). Serum GH was measured by immunoradiometric assay using "Daiichi kit"(Je Il Pharmaceutical Co., Japan). Wilcoxon ranked sum test and student's t-test were used to assess the significance of differences between the groups of the patients. The correlation between urinary GH level and peak serum GH level was assessed by the parametric Pearson correlation test. The correlation between peak serum GH level in GH provocation test using insulin and urinary GH level measured by overnight 10 hours collection method showed statistically significant results in all the patients(Y=0.464072X +9.208044, r=0.48987, p=0.0001) and in the GH deficiency groups(GCD+GPD) (Y=0.924659X +9.2385509, r=0.80437, p=0.0001). In case of L-dopa stimulation test, urinary GH values were also positively correlated with peak serum GH level when all the patients were participated(Y=0.572988X +8.312993, r=0.58212, p=0.0001). In contrast, no correlation was found when patients were confined to GH deficiency group(GCD+GPD)(Y=0.127712X +8.3129939, r=0.08044, p=0.6841).

Clinical Effects of E. coli Derived Recombinant Human Growth Hormone (DA - 3001) in Patients with Growth Hormone Deficiency.: Sei Won Yang, Jeh Hoon Shin, Duk Hi Kim, Byung Churl Lee, Hyung Ro Moon; J Korean Endocr Soc. 1995;10(4):377-385. Published online November 7, 2019

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Abstract PDF: Recently, methionyl-hGH was produced in the E. coil K-12, W3110 by recombinant DNA technology in Korea. In this paper, the clinical efficacy and immunogenicity of this GH were studied in 43 patients with growth hormone deficency.The subjects of this study were aged 4.3-18.5 years and each patient received GH 0.5-0.71U/kg week subcutaneously, 6-7 times a week for 1 year. During treatment, height, body weight and bone age were checked. Blood count, urinalysis, blood chemistry and thyroid hormonal concentrations were checked before and every 3 months. The measurement of IGF-1 was performed and assay of antibody against hGH was performed before and every 6 months.The height velocities significantly increased from 3.7+-3.0 cm/year to 11.0+-4.2 cm/year and 9.9+-3.2 cm/year at 6 and 12 months after GH therapy, respectively. The Height SDS were significantly improved after GH therapy with increasing ratio of bone age to chronological age from 0.60+-0.19 at pretreatment to 0.68+-0.16 at 6 month, 0.69+-0.16 at 12 month of therapy. The plasma IGF-1 levels significantly increased during treatment. Three out of 35 patients(8.3%) showed antibody against hGH after 1 year of treatment. Thoughout study, we could not observe any remarkable side effect with GH treatment.These results indicate that this E. coli derived methionyl recombinant growth hormone is effective in improving the index of linear growth in the children with growth hormone deficiency without significant side effect.

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.

Insulin Like Growth Factor-I and Insulin Like Growth Factor Binding Protein-3 in Human Thyroid Cystic Fluids.: In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Byoung Joon Kim, Seung Joon Oh; J Korean Endocr Soc. 1995;10(4):395-404. Published online November 7, 2019

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Abstract PDF: In the thyroid tissue, thyrotrophin(TSH) and IGF-I played major role of the goitrogen. But the evidences and precise mechanism of these two factors were not known so much. Actually local secretion of thyroid IGF-I was originated from its fibroblasts mainly. We guessed major roles of IGFs in the thyroid tissue were local paracrine effect of thyroid cells proliferation and differentiation which concert with TSH. Recently, some reporters described the source of thyroid IGF-I were partly from thyroid follicular cells and its action were synergistic with TSH. We measured TSH, IGF-I and IGFBP-3 from sera and thyroid cystic fluids in 36 patients with simple thyroid cyst and examined into correlation between TSH, IGF-I and IGFBP-3.1) According to cyst/serum TSH ratio, we classified two groups(Group I; c/s TSH <1, n=19. Group II; c/s TSH >1, n=17). This classification criteria means that cystic TSH level were increased than that of serum or not.2) The serum TSH, IGF-I and IGFBP-3 levels are not difference between group I and II.3) Cystic TSH were dependent on the serum TSH in Group I, but negative correlation in Group II. In Group II, cystic TSH was significant increased.4) Serum IGF-I were positive correlation in each Group5) In Group II, cystic IGF-I was not exceed than those of serum IGF-I, but some cystic IGFBP-3 were more increased than those of serum.6) In Group II, cystic IGFBP-3 increased than serum TSH, and cystic IGFBP-3 was positive correlation with cystic TSH and cystic IGF-I.As these data suggested that cystic TSH and cystic IGF-I levels may influence cystic IGFBP-3 level. The main effect for maintenance of cyst was mediated by cystic TSH and cystic IGFBP-3. But the cystic IGFBP-3 has major role for thyroid cyst than cyst TSH.

Correlation between Serum Levels of ICAM-1 and Serum Levels of Thyroid Hormones, TSH - Receptor Antibodies or Levels of IL-6 of Peripheral Blood Monocyte in Graves' Disease.: Keun Yong Park, Deok Jun Kim; J Korean Endocr Soc. 1995;10(4):405-410. Published online November 7, 2019

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Abstract PDF: Lymphocytic infiltration of the thyroid gland is a hallmark of the human thyroid autoimmune disease. Enhanced expression of immunoglobulin and adhesion molecules are consistently found in patients with autoimmune thyroid diseases. And cytokines are implicated in enhancing the expression of adhesion molecules.It has been suggested that adhesion-molecule expression within thyroid glands mediates lymphocyte homing events to the target of the autoimmune process. The expression of ICAM-1 was shown to be up-regulated on thyroidal perifollicular endothelial cells and thyrocytes in autoimmune thyroid diseases both in vitro and in vivo.Therfore, we investigated the correlation between thyroid hormone, TSH receptor antibodies, Interleukin-6 and soluble ICAM-1 in patients with Graves' disease before and 2 months after treatment with prophylthiouracil(PTU).Serum concentrations of soluble intercellular adhesion molecule-1(sICAM-1), T_3, T_4, TSH-receptor antibodies(TSH-R-Ab) and Interleukin-6(IL-6) of peripheral blood monocytes were measured in patients with Graves' disease.Serum levels of sICAM-1 were elevated in patients with Graves' disease before treatment with PTU, but serum levels of sICAM-1 did not correlate with the serum concentration of thyroid hormone and TSH-R-Ab before and after treatment. In addition, no correlation between serum levels of sICAM-1 and IL-6 of peripheral blood monocyte.We conclude that although the elevated serum levels of sICAM-1 may contribute to the autoimmune process in Graves' disease, we need more future studies for the role of sICAM-1 and correlation between adhesion molecule and thyroid hormone or cytokines in patients with Graves' disease.

Estrogen Replacement Therapy Continuously Combined with Progesterone; Effect on Bone Mineral Density and Lipid Metabolism.: Keun Yong Park; J Korean Endocr Soc. 1995;10(4):411-417. Published online November 7, 2019

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Abstract PDF: A study in 51 healthy postmenopausal women was performed to assess the effect of estrogen replacement therapy continuously combined with progesterone for 6 months on bone mineral density and lipid metabolism.Seventeen hysterectomized women were treated with conjugated estrogen(0.625mg/D), 33 nonhysterectomized women with conjugated estrogen(0.625mg/D) and medroxyprogesterone(2.5mg/D), and 1500mg/day calcium supplementation was given to all patients.After 6 month-treatment, serum total cholesterol and LDL-cholesterol levels were reduced significantly (p<0.01) between the two groups. But lumber BMD and other lipid profiles were not changed significantly between the two groups. Our data suggest that continuously applied progesterone in combined hormone replacement therapy dose not annihilate the beneficial effects on bone mineral density and lipid metabolism induced by estrogen.

Case Reports

A Case of Anterior Cervical Lipoma Mimicking Diffuse Goiter.: Eun Jig Lee, Moon Suk Nam, Su Youn Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Jun Sik Na, Yee Hyun Nam, Jeon Hong Kang, Jung Ki Seo; J Korean Endocr Soc. 1995;10(4):418-423. Published online November 7, 2019

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Abstract PDF: Lipoma is a benign fatty tumor that can arise in any location of the body where fat is present. It is found most commonly in the upper half of the body, particularly the head and neck, shoulders, and back. A mass in the antero-inferior part of the neck may be initially thought to be thyroid masses and then other cervical masses should be considered. Ultrasongraphic examination of benign lipoma demonstrates solid and echogenic mass and may differentiate nonthyroid from thyroid masses. Although the location of tumors, its consistency, and its motion with deglutition, seperation from the thyroid on sonographic examination, all pointed to nonthyroidal origin, did not rule out a possible mass that isolated from the lobes of the thyroid. Fine needle aspiration and biopsy can provide clear answer.We herein report a case of anterior cervical mass in a 48-yr-old male patient presenting a non-tender, slightly hard and nodular mass slowly growing for several years and moved with swallowing, and diagnosed his case as benign lipoma using thyroid scan and ultrasonography. When we encounter patients with anterior neck mass, we should consider benign lipoma mimicking diffuse goiter.

A Case of Thyrotoxic Hypokalemic Periodic Paralysis Presenting as Cardiac Arrest.: Chang Ho Song, Choon Hee Chung, Young Joon Weon, Mi Deok Lee, Seong Jin Park, Young Goo Shin, Won Sik Lee; J Korean Endocr Soc. 1995;10(4):424-427. Published online November 7, 2019

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Abstract PDF: Periodic paralysis associated with thyrotoxicosis is characterized by intermittent flaccid paralysis of the skeletal muscle. The paralysis usually involve the skeletal muscle of the limbs, especially lower extrimities. In general, sensory function is intact. Involvement of respiratory, ocular or bulbar muscles is very rare, but bulbar and respiratoy invelvement may prove fatal. It is very rare a case that has severe clinical manifestation such as cardiac arrest. We report a case of thyrotoxic hypokalemic periodic paralysis presenting as cardiac arrest.

Tuberculosis of the Thyroid Gland.: Chang Ho Song, Choon Hee Chung, Young Joon Weon, Mi Deok Lee, Seong Jin Park, Won Sik Lee, Mee Yon Cho, Young Kyung Kim, Seung Min Kim, Seong Joon Kang; J Korean Endocr Soc. 1995;10(4):428-433. Published online November 7, 2019

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Abstract PDF: Tuberculosis the thyroid gland occurs only rarely and a few records are available in Korea, despite of high prevalence of tuberculosis. The authors experienced a case of young woman with tuberculosis of the thyroid gland and meninges. Tuberculosis of the thyroid gland was confirmed by demonstration of acid-fast bacilli and granuloma with caseation necrosis on surgical specimen. Description of case profile and a brief review of literature are made.

Original Article

A Case of Insulinoma without Peripheral Hyperinsulinemia.: S W Park, J G Chae, C C Choi, S K Lee, K U Lee, D J Han, I C Lee, K B Sung, S H Kim, Y K Shong, J Y Park, G S Kim; J Korean Endocr Soc. 1995;10(4):434-438. Published online November 7, 2019

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Abstract PDF: Insulinoma is a disorder characterized by hypoglycemia due to endogenous hyperinsulinemia. The elevated plasma insulin level and hypoglycemia should be established for the diagnosis of an insulinoma. Other laboratory methods such as immunoreactive insulin to glucose(IRI/G) ratio, C-peptide, proinsulin, and some provocation tests are also employed to detect an insulinoma because hyperinsulinemia is often not found. Especially, IRI/G ratio has been considered as very sensitive and specific test to confirm the insulinoma without peripheral hyperinsulinemia. We report a case of insulinoma without hyperinsulinemia and elevation of IRI/G ratio, which was diagnosed by endoscopic ultrasonography and THPVS(Transhepatic portal venous sampling). It is suggested that more confirmatory tests will be necessary for the diagnosis of insulinoma especially when it is highly suspected although IRI/G ratio is not increased.

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