Endocrinology and Metabolism

Volume 9(3); September 1994

Review Articles

G Protein Oneogenes in Aeromegaly.: Eun Jig Lee, Hyun Chul Lee; J Korean Endocr Soc. 1994;9(3):157-162. Published online November 6, 2019

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Abstract PDF: No abstract available.

Role of GTP - binding Protein in Signal Transduction.: Bong Yun Cha; J Korean Endocr Soc. 1994;9(3):163-179. Published online November 6, 2019

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Abstract PDF: No abstract available.

Editorial

Pregnancy and Thyroid Disease.: Youn Bok Chang; J Korean Endocr Soc. 1994;9(3):180-182. Published online November 6, 2019

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Abstract PDF: No abstract available.

Original Articles

Changes of Thyroid Function According to the Stages of Normal Pregnancy.: W B Kim, B H Yoon, J H Chung, S I Lee, M S Kim, T G Oh, B Y Cho, H K Lee, C S Koh; J Korean Endocr Soc. 1994;9(3):183-189. Published online November 6, 2019

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Abstract PDF: It is well known that normal pregnancy is accompanied by a rise in serum concentrations of thyroxine-binding globulin(TBG) and human chorionic gonadotropin (hCG). Alterations of biochemical parameters of thyroid function are recognized during gestation and sensitive tests to evaluate the alterations easily are required. Therefore, a cross-sectional study was undertaken in 140 healthy pregnant women to evaluate the efficacy of free T_4 measured by 2-step RIA compared to other thyroid function tests and to confirm the changes of thyroid function according to the stages of normal pregnancy.The sensitivities of free T_4 index, free T_4(by 2-step RIA), T_3 and TSH were realtively high(99.3%, 93.6%, 92.9%, 83.6%, respectively) compared to those of T_4 and T_3 bead upgake(49.3%, 21.4%) during all stages of pregnancy. There were positive correlations between free T_4 index and free T_4 or total T_4(r=0.68, r=0.72; p<0.001). The values of free T_4 index sharply decreased from 3.22+-0.10(meam +-SEM) during 6th-12th week to an plateau after 16th-20th week of gestation(p<0.01). The serum concentrations free T_4 and T_3 bead uptake also significantly decreased from 1.65+-0.05 ng/dl, 24.7+- 0.7% during 6th-12th week to an plateau after 16th-20th week of gestation, respectively(p<0.001), No differences were found in the changes of serum concentrations of T_3, T_4 and TSH according to the stages of pregnancy.In conclusion, it is adequate to measure some tests including free T_4 index and free T_4 to evaluate thyroid function during pregnancy. The thyroid physiology and changes of thyroid function according to the stages of pregnancy should be considered in the interpretation of thyroid function status during pregnancy.

Characterization of Cyclic AMP Response Element (CRE) in the Promoter of the Rat Thyrotropin Releasing Hormone (TRH) Gene.: Woon Won Jung, In Myung Yang, Kwang Sik Seo, Seok Won Jung; J Korean Endocr Soc. 1994;9(3):190-199. Published online November 6, 2019

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Abstract PDF: We investigated whether the two variant elements of CRE(TGcCGTCA[5'CRE], TGACcTCA[3'CRE]) in the 5'flanking region of the rat TRH gene, which are different from the CRE consensus sequence(5'-TGACGTCA-3') by one base pair, are responsive to cAMP, and whether the one base pair difference is responsible for the degree of cAMP responsiveness of the gene. When CA 77 cells were stimulated with forskolin and isobutylmethylxanthine for 4 hours, the level of TRH mRNA was increased by only two fold. The transient gene expression study using serial 5'deletion of the TRH gene in PC12 cells showed that the region between-113 and-77, which includes 5'CRE, was crucial for the cAMP resonsiveness. When the plasmid, which contains the 30 bp oligonucleotide including either 5'CRE or 3'CRE ligated to the enhancerless RSV promoter, was transfected into PC12 cells, it did not significantly affect not only the basal transcription but cAMP responsiveness. The 65 bp oligonucleotide including both 5'CRE and 3'CRE, however, increased both of the basal transcription and cAMP-stimulated transcription by 2-3 fold. When the sequence of 5'CRE was converted to that of the CRE consensus by replacing one base pair, the cAMP responsiveness was increased by two fold although the basal transcription was not increased. The one base pair mutant of 3'CRE increased both of the basal and cAMP-stimulated transcription by 3-4 fold. These results suggest that there are the two variant CREs in rat TRH gene, which are relatively weak CRE compared to the CREs of other neuropeptide genes and cooperative for the activation of both the basal and cAMP-stimulated transcription. The one base pair difference of the variant CREs from the CRE consensus sequence is responsible for the weak responsiveness to cAMP.

Endocrinological and Morphological Characteristics of Clinically Nonfunctioning Pituitary Adenoma.: Jae Wha Jo, Moon Suk Nam, Hyun Chul Lee, Tae Seung Kim, Kyu Chang Lee, Hyun Joo Jung; J Korean Endocr Soc. 1994;9(3):200-212. Published online November 6, 2019

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Abstract PDF: Forth-nine patients with clinically nonfunctioning pituitary adenomas were evaluated clinically, endocrinologically and morphologically in this study.The results obtained were as follows.1) The mean age was 47.1 years(range 23 to 76 years), and 22 were male(44.9%) and 27(55.1%) female.2) The major clinical manifestations of male patients were visual disturbance(72.7%), headache(54.5%), loss of libido(45.5%), but those of female visual disturbance(59.6%), headache(48.1%), amenorrhea(48.1%), loss of body hair(25.9%), and galactorrhea(22.2%).3) All were macroadenomas evaluated by CT scan, and in the male patients 16(72.7%) were grade III and 6(27.3%) grade IV by Hardy classification, and in the female patients 6(22.2%) were grade II, 12(44.4%) grade III, and 9(33.3%) grade IV.4) The elevation of serum prolactin were observed 7(31.8%) out of male, and 24(88.9%) of female.5) Combined stimulation test revealed that GH insufficiency was 89.6%, ACTH 58.9%, LH 58.7%, FSH 51.1 %, and TSH 50.0% and hormone insufficiency more than 4 pituitary hormone was 54.2%.6) Prolactin response to TRH decreased in 12(70.6%) of 17 patients with normal basal prolactin, and 19(76.0%) of 25 with elevated prolactin.7) Immunohistochemistry revealed that null cell adenoma was 57.1%, gonadotrope adenoma 26.5%, plurihormonal adenoma 8.0%, silent corticotrope adenoma 4.0%, thyrotrope adenoma(2.0%), and lactotrope adenoma(2.0%).8) The ultrastructural characteristics examined by electron-microscopy were similar despite of immunohistochemical differences.In summary, the prevalance of clinically nonfunctioning pituitary adenoma was middle aged men and women, and their main symptoms were visual disturbance and headache. Hyperprolactinemia and pituitary hormone insufficiency more than 4 hormone were observed commonly. Most of them were null cell adenoma and gonadotrope adenoma examined by immunohistochemistry. Further study using modern techniques: cell culture, subunit-immunostaining. And Northern blot analysis of mRNA for pituitary hormone or subunit, will be needed to clarify null cell adenomas.

Effect of Insulin Like Growth Factor - 1 (IGF - 1) on Energy Restricted Rat - Failure of IGF - 1 injection to promote growth in energy restricted rats despite normalization of serum IGF - 1 concentration -.: Jeh Hoon Shin; J Korean Endocr Soc. 1994;9(3):213-218. Published online November 6, 2019

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Abstract PDF: recombinant human IGF-I in energy-restriction model. Experimental design; Sprague-Dawley rats(n=20) weighing 90-100g were used. Rats were fed a control diet two times a day(AM 8-11, PM 5-8) for four days after arrival and then assigned to one of three groups: control, energy-restricted, energy-restricted IGF-I treatment group. Energy restricted group was given with a decrese of 25% in the energy without changes in the protein by feeding 88% by weight to energy-restricted diet. During the 10days of energy restriction, the growth rate was reduced by 35%(2.70+-0.18g/day in energy restricted group vs. 4.13+-0.75g/day in the control group). At sacrifice, the tail lengh and weight of organs were not significantly decreased except the spleen and thymus(-17%: P<0.05). Serum IGF-I was reduced by 19% at the end of 10days of energy restriction. The glycemia, measured each day by glucometer from blood collected at the tail, was not reduced by energy restriction(105.4+-7.7 in control group vs. 101.3+-4.1mg/dl). The abundance of serum IGF-BPs was unchanged by this restriction.Despite the 1.5 fold increase of IGF-I concentration in energy restricted IGF-I injection group at sacrifice(1994+-172ng/ml vs. 1221+-110 ng/ml energy restricted group), IGF-I treatment(300 ug/day in twice sc injection for 6day) did not significantly accelerate the growth rate(body weight)(2.87+-0.20 vs. 2.70+-0.18g/day in energy restricted group).The glycemia was slightly reduced by IGF-I treatment(91.7+-5.0 mg/dl vs. 101.3+-4.5 mg/dl in energy restricted group), but it was not significant. However, the spleen and thymus weight, decreased by energy restriction, was completely normalized by IGF-I treatment.In summary, lack of a significant anabolic response to injection of IGF-I during energy restriction in this study may be associated with the compensatory growth response(alterations in dietary protein utilization) which followed initial period of energy restriction.

Molecular Genetic Studies on the Human CYP21A2 Gene (1).: Byung Kiu Park, Hyang Ok Woo, Han Wook Woo; J Korean Endocr Soc. 1994;9(3):219-227. Published online November 6, 2019

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Abstract PDF: Congenital adrenal hyperplasia, especially due to steroid-12-hydroxylase(P450c21) deficiency, is one of the most common autosomal recessive inborn errors at adrenal steroidogenesis in Korean. Molecular genetic analysis has demonstrated that there are two steroid 21-hydroxylase genes, CYP21A1P and CYP21A2. The CYP21A2 gene encodes P450c21, whereas the CYP21A1P gene is a pseudogene. Since there is 98 percent homology between the CYP21A1P and CYP21A2 gene in nucleotide sequences, it has hampered the characterization of molecular defects in the CYP21A2 gene.In this study, efforts have been made to selectively PCR amplify the CYP21A2 gene and test feasibility of DNA microextraction from Guthrie card for prospective use of molecular screening. This study was also aimed at investigating deletion mutations in P450c21 deficient patients, as well as allele frequencies and average heterozygosity of exon 1 A/C polymorphism in Korean newborns. Genomic DNAs were obtained from Guthrie cards of 50 Korean newborns by microextraction method and these DNAs were analyzed by PCR-allele specific oligonucleotide(ASO) hybridization. First part of the CYP21A2 gene has been successfully amplified and digested by restriction enzyme using Taq I or Kpn I, subsequently run on 1.5% agarose gel to confirm its specificity. The anterior 1141 bp PCR product was utilized to examine the frequency and average heterozygosity of exon 1 A/C polymorphism in 100 alleles by ASO dot blot hybridization. Amplified genomic DNAs from four P450c21 deficient patients out of three families were screened by PCR to see if any one has complete deletion of the CYP21A2 gene.The results were as follows;1) The average 1230ng of genomic DNA was obtained form single semi-circled Guthrie card of 1/2 inch diameter by microextraction method, which has been successfully used for DNA analysis.2) The PCR amplified anterior 1141 bp product from the CYP21A2 gene was digested by Kpn I, generating 309 bp, 832 bp fragments, not by Taq I, indicating its specificity.3) The frequencies of exon 1 nucleotide 138 A/C polymorphism in Korean population were 0.81, 0.91 respectively, and average heterozygosity was 0.31.4) None of four P450c21 deficient patients turned out to carry complete deletion of the CYP21A2 gene based on selective PCR amplification of the CYP21A2 gene.In conclusion, dried blood spots from Guthrie card can be sued for DNA analysis because of easy sample collection, bandling, shipment, and DNA extraction feasibility. The selective PCR amplification of the CYP 21A2 gene will pave the way for molecular characterization in P450c21 deficient patients. The exon 1 A/C polymorphism can by efficiently used for molecular diagnosis of P450c21 deficiency in informative families, though it has a drawback of handling radioactive material.

A Clinical Observation of Endocrine Adrenal Tumors.: Hye Young Park, Tae Suk Kim, Soo Jin Lee, Dong Gu Choi, Moon Ho Kang; J Korean Endocr Soc. 1994;9(3):228-238. Published online November 6, 2019

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Abstract PDF: Endocrine adrenal tumors are uncommon but clinically significant because they can be managed successfully by surgical therapy. During pregnancy, adrenal tumors can be a cause of death for both mother and baby, unless they diagnoses antenatally and managed properly. To investigate clinical characteristics of endocrine adrenal tumors, we analyzed 26 cases of adrenal tumor diagnosed and managed in Chung Ang Gil Hospital including cases associated with pregnancy and also a rare case of paraganglioma in liver. 1) There were 7 cases of Cushing's syndrome among which two cases were due to Cushing's disease and five cases were due to adrenal adenoma. Six cases were managed successfully by appropriate surgery. Another one case was associated with pregnancy but the patient expired due to sudden development of pulmonary edema and hypotension during preoperative preparation.2) Among 9 cases of primary aldosteronism, 8 cases were aldosterone-producing adenoma(APA) and 1 case was idiopathic hyperaldosteronism(IHA). In differential diagnosis between APA and IHA, diagnostic accuracy of postural study and adrenal CT was 86%, 78% respectively. In each one case of APA and IHA, adrenal venous aldosterone sampling was used for the differential diagnosis. Six cases of APA were managed by appropriate surgery. One patient with APA who refuses surgery and one patient with IHA were placed on spironolactone with good response.3) Among 10 cases of pheochromocytoma, seven cases were from adrenal gland and three cases were paragangliomas including one case originating from liver and two cases from abdominal ganglia. One patient with pheochromocytoma was diagnosed in 1st trimester of pregnancy and she was successfully treated by surgery.We observed 26 cases of endocrine adrenal tumors which were successfully managed except one case. We think that it is important to pay attention to adrenal tumor for early diagnosis particulary when associated with pregnancy. Paraganglioma in liver, although very rare, should be included in the differential diagnosis of space occupying lesion in liver.

A Case of True Precocious Puberty Associated with Pituitary Microadenoma Treated with LHRH Agonist.: Ho Jung Kim, In Soon Kim, You Hern Ahn, Mok Hyun Kim, Jea Ung Lee, Jin Ho Kim, Ik Soo Park, Ho Joo Yoon, Choon Suhk Kee, Sung Soo Park, Jung Hee Lee; J Korean Endocr Soc. 1994;9(3):239-243. Published online November 6, 2019

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Abstract PDF: Although tubercrlosis is one of the recognized causes of adrenal insufficiency, little is known about adrenal function in patients with active pulmonary tuberculosis. Patients with active pulmonary tuberculosis are at risk from sudden and unexpected death which can occur during the first few weeks of treatment. There are many reports that patients who received rifampicin as a part of their treatment appeared to show impairment in adrenocortical function when compared to a group who received anti-tuberculosis chemotherapy which did not include rifampicin. Adrenocortical function was studied in 15 patients(7 males, 8 females) with active pulmonary tuberculosis, before and 2-weeks after the anti-tuberculosis chemotherapy including rifampicin. At 08: 00 hour a base-line sample of venous blood was taken. One hour after the administration of 0.25mg of Synacthen, a further blood specimen was taken. The base-line and 1-hour specimens were analysed for plasma cortisol and electrolytes.All were initially found to have a normal cortisol response to rapid ACTH stimulation test. Following a 2-week course of anti-tuberculosis chemotherapy including rifampicin there was 1 case(6.6%) of a suboptimal response.Rifampicin, a powerful anti-tuberculosis drug, is a known inducer of the hepatic microsomal enzyme system and has been shown to cause an enhanced clearance of endogenous cortisol. Findings reported in this paper suggest that the adrenocortical function is compromised in some case(6.6%) of tuberculosis patients. It will therefore be necessary to undertake detailed investigations on the effect of treatment with daily and fully intermittent regimens containing rifampicin on the function of this endocrine gland.

Case Reports

A Case of True Precocious Puberty Associated with Pituitary Microadenoma Treated with LHRH Agonist.: In Kyu Lee, Soon Woo Kim, Heung Sik Kim, Chin Moo Kang; J Korean Endocr Soc. 1994;9(3):244-250. Published online November 6, 2019

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Abstract PDF: Recently Brain CT and MRI have greatly contributed to the discovery of intracranial tumors including cysts which cause precocious puberty. Among many precocious pubetry patients that had previously been diagnosed as idopathic, a number of cases turn out the true precocious puberty caused by intracranial lesion.Authors experienced a case of true precocious puberty in a seven year old female whose vaginal bleeding appeared at age of five and she also had breast enlargement on admission. Pituitary microadenoma was found on her brain MRI and the microadenoma turned to be nonfunctional on hormonal tests.Following three does of decapety1-CR(LHRH Agonist), the vaginal bleeding was ceased and the deceleration of breast enlargement was noted. Her growth velocity was also affected but the further observation for final height would be warranted.

Primary Hyperparathyroidism in Children.: Han Sang Cho, Sang Ook Park, Byung Mun Lee, Yung Tak Lim, Su Yung Kim; J Korean Endocr Soc. 1994;9(3):251-257. Published online November 6, 2019

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Abstract PDF: Primary hyperparathyroidism is a rare endocrine disease in children. It involves bone and joint, urinary tract, gastrointestinal tract and cardiovascular system. The main cause of these involvement is high level of PTH in serum, resulting in hypercalcemia.An 11 years old male patient who had complained of limping gait since last 18 months, showed typical laboratory and radiological findings of primary hyperparathyroidism. At the ultrasonography, computed tomography and radionuclide scanning, a well defined mass(10 X 15mm) was found on the posterior aspect of the right thyroid lobe. The mass was confirmed histologically as adenoma of parathyroid gland. The patient was successfully treated with subtotal parathyroidectomy and temporal administration of calcium and vitamin D.We report this case of primary hyperparathyroidism with brief review of the literatures.

A Case of Autonomously Functioning Thyroid Nodule Treated with Percutaneous.: Min Ho Shin, Chun Hee Koo, Young Ju Park, Jeong Yim Lee, Tae Yong Park, Eun Sil Kim, Jong Soon Kim, Seung Soo Han; J Korean Endocr Soc. 1994;9(3):258-264. Published online November 6, 2019

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Abstract PDF: Autonomously functioning thyroid nodules(AFTNs) are so named because they presumably are independent of TSH for growth and function. In general, surgery and radioactive iodine are effective therapies but reluctant to use because of complications such as hypothyroidism or cosmetic problems.Percutaneous ethanol injection therapy(PEIT) under sonographic guidance has recently been introduced as alternative therapy. But its adverse effects such as severe local pain, subcutaneous hematoma or palsy of the recurrent nerve are not negligible, therefore sufficient skill is required.In this case, the levothyroxine therapy in reducing the size of colloid thyroid nodules was not apparent within three months. Therefore we selected another sclerosing therapeutic method such as percutaneous tetracycline injection(PTI) and followed up thyroid function test, thyroid scan, ultrasonographical size and volume of nodule. The results were as follows: 1) With 0.5-0.8 cc tetracycline injection for three times, the volume of nodule was reduced after PTI; About 2.3 X 1.7 X 0.7 cm sized nodule was reduced to about 1.3 X 1.0 X 0.5 cm sized nodule. 2) There were significant improvements of TFT(subclinical hyperthyroidism to euthyroidism) and thyroid scan(solitary hot nodule to completely ablated AFTN) during 9 months follow-up after PTI as compared with the base line study. In conclusion, we experienced good results in a 22-year-old woman suffered from AFTN treated with PTI and think that PTI could be the effective, safe, simple, well tolerable procedure in the treatment of AFTN.

A Case of Insulinoma Diagnosed as Epilepsy for 7 Years.: Jong Su Kim, Hyung Gyung Choi, Eun Suk Choi, Soo Ryong Jung, Chung Huh, Jin Kwan Lee; J Korean Endocr Soc. 1994;9(3):265-271. Published online November 6, 2019

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Abstract PDF: Insulinoma is rare functioning islet cell tumor of pancreas and its main feature is frequent attacks of hypoglycemia. Because of frequent seizure, the disease is occasionally mistook as epilepy. We experienced a case of insulinoma with dilantin toxicity in a 45 year old patient who had been treated with dilantin for 7 years. Selective splenic arteriogram showed 0.8cm mass in the tail of pancreas which was proven insulin secreting tumor on histiopathological examination. After operation no more seizure attack was detected and her blood sugar level was well maintained within normal range. This case might provide an insight that the possibility of insulinoma should be considered in patient with episodic neurobehavioral dysfunction such as epilepsy.

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