HIT 세포에서의 Dexmethasone 이 글루코키나제와 글루코기나제 mRNA 발현에 미치는 영향

안규정(Kyu Jeong Ahn),김덕윤(Deok Yoon Kim),우정택(Jeong Taek Woo),김성운(Sung Woon Kim),양인명(In Myung Yang),김진우(Jin Woo Kim),김영설(Young Seol Kim),김광원(Kwang Won Kim),최영길(Young Kil Choi) 대한내과학회 1994 대한내과학회지 Vol.46 No.4

N/A Objectives: The glucokinase-glucose sensor concept of physiological glucose recognition by pancreatic beta- cells has developed progressively since the presence of this enzyme in beta-cells was first reported in 1968. It is well known that HIT cells have glucokinase activity and then insulin secretory response according to glucose stimulation, but there are few data about the effect of hormone on insulin secretion and glucokinase in HIT cells. Therefore, we studied the effect of dexamethasone on glucokinase activity, mRNA expression and insulin secretion in HIT cells. Methods: HIT cells were cultured for 24 hours in medium containing 0, 50, or 500 nM dexamethasone, and then the activities of glucokinase was quantitiated using pyridine uncleotide-dependent fluorometric assays. Northern blot analysis of glucokinase mRNS was done. Results: 1) The Vmax and Km of glucokinase in HIT cells were 3.5 μ mol/min/mg protein, 0.77 mM in HIT cells exposed to 7 mM glucose, respectively and the Vmax and Km of hexokinase in HIT cells were 2.64 μmol/ min/mg protein, 0.06 mM, respectively. 2) 24 hours after incubation of HIT cell with dexamethasone 0, 50, 500 mM, the glucokinase activity and insulin secretion were observed: the glucokinase activities were 1.4±0.45(control), 0.87±0.43(50nmol dexarnethasone), 0.13±0.52 uU/mg protein(500 nmol dexamethasone), and insulin secretion were 44.57±4.1(control), 35.50±1.72(50 nmol dexamethasone), 31.62±1.07 ng/mg protein(500 nmol dexamethasone), respectively. 3) Northern analysis revealed that dexamethaxone increase glucokinase mRNA expression according to dexamethasone concentrations 24 hours after incubation of HIT cells with dexamethasone 50 or 500 nM. Conclusion: Our data showed that dexamethasone tended to increase glucokinase mRNS expression, but decrease glucokinase activity and insulin secretion in HIT cells. Thease data suggested that dexamethasone may have an variable effect on transcriptional or posttranslational levels of glucokinase.

한국인의 비만과 인슐린비의존성당뇨병에서 베타-2 아드레날린 수용체 유전자 다형성

김병준(Byoung Joon Kim),안규정(Kyu Jeong Ahn),김영설,최영길,이문규,김성훈(Sung Hoon Kim),김동준(Dong Jun Kim),함종렬(Jong Ryeal Hahm),정재훈(Jae Hoon Chung),민용기(Yong Ki Min),이명식(Myung Shik Lee),김광원(Kwang Won Kim) 대한내과학회 1999 대한내과학회지 Vol.56 No.4

N/A Objective: Catecholamine play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells. The beta-2 adrenergic receptor(BAR-2) is a major lipolytic receptor in human fat cells. A recent study has shown that common polymorphisms occuring at codon 16 and 27 of the BAR-2 gene are significantly associated with obesity and lypolytic BAR-2 function in adipose tissue. We investigated whether the previously described human BAR-2 gene polymorphisms are associated with obesiy and NIDDM in Koreans. Methods : All subjests were divided into two groups, non-obese and obese group, according to their body mass index. And their clinical characteristics were evaluated. The BAR-2 gene polymorphisms were analyzed by PCR-RFLP in 89 nondiabetics and 106 patients with NIDDM. Results : When the allele frequency of BAR-2 gene polymorphisms was compared with that of western people, there was a significant difference. In our study, there was no significant difference in the allele frequency of BAR-2 gene polymorphisms at codons 16 and 27 between nonobese and obese group both nondiabetics and NIDDM subjects. The frequency of Glu27 homozygotes was very rare(1.1%). Body mass index(BMI), waist-hip ratio(WHR), and serum glucose and insulin secretion of the nondiabetics with polymorphism of codon 16 or codon 27 did not differ from those of the subjects without the polymorphisms. In NIDDM group, the Gly16 homozygotes had a lower BMI than Arg16 homozygotes without any difference in WHR and the other laboratory parameters. Neither clinical or laboratory parameters of the diabetics with the polymorphism at codon 27 differ from those of subjectes without the polymorphism. Conclusion : These findings suggest that the genetic variability in the human BAR-2 gene is not a major determinant for the development of obesity and NIDDM in Koreans.

폐경 전 여성에서 혈청 비타민 D 농도와 인슐린 저항성에 관한 연구

이지혜(Ji-Hye Lee),홍준화(Jun-Hwa Hong),김현진(Hyun-Jin Kim),박강서(Kang-Seo Park),이재민(Jae Min Lee),김병준(Byung-Joon Kim),안규정(Kyu-Jeung Ahn),정비오(Bi O Jeong),김성환(Sung-Hwan Kim),이성규(Seong-Kyu Lee) 동아시아식생활학회 2009 동아시아식생활학회지 Vol.19 No.5

쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

임신 중 진단되어 분만 후 부신피질선종을 제거한 쿠싱증후군 1예

조정수,전재석,안규정,김병준,권성호,이은규,최원욱,박상원,이원미 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.5

임신과 동반하는 쿠싱증후군은 매우 드물며 임신자체가 쿠싱증후군과 유사한 임상양상을 보이고 생화학적으로도 그 감별은 쉽지 않다. 뇌하수체의존성 쿠싱증후군이 자연적으로 발생하는 쿠싱증후군의 가장 많은 원인을 차지하는 것과 달리, 임신과 동반되는 경우 전체의 약 반수에서 부신피질선종이 그 원인으로 알려져 있다. 그 치료로 임신 2기 중 수술적 치료가 권고되고 있으나 코티졸 생성을 감소시키는 약물치료를 포함한 보존적 치료를 분만 때까지 시행하고, 분만 후 수술적 치료를 시행하여 산모와 태아에 좋은 결과를 보인 예들 또한 보고되고 있다. 저자 등은 임신 25주 에 고혈압, 심부전으로 인한 폐부종, 당뇨병 등으로 내원하여, 내분비학적 검사와 방사선학적 검사에 의해 부신피질선종에 의한 쿠싱증후군으로 진단된 후 심부전 치료, 혈압 및 혈당조절, 스테로이드생성 억제제 등 보존적 치료를 유지하여 분만 후 부신피질선종을 제거한 산모 1예를 경험하였다. Pregnancy is rare in women with Cushing's syndrome, as the associated infertility is related to excess cortisol and/or androgen. However, approximately 100 such cases have been reported, with 50% due to an adrenal cortical adenoma. Establishing a diagnosis and cause can be difficult. Clinically, striae, hypertension and gestational diabetes are common features in pregnancy, with hypertension and diabetes being the most common signs of Cushing's syndrome in pregnant women. Furthermore, biochemically, a normal pregnancy is associated with a several fold increase in plasma cortisol, as the increased cortisol production rate also increases the cortisol binding protein. Untreated, the condition results in high maternal and fetal morbidity and mortality. An adrenal or pituitary adenoma should be excised, but a metyrapone, which is not teratogenic, has been effective in controlling many cases of excess cortisol. Here, a case of Cushing's syndrome, complicating a pregnancy due to an adrenal cortical adenoma, with thorough obstetric and medical management, including a metyrapone, which was adrenalectomized after delivery, is reported (J Kor Soc Endocrinol 18:489∼495, 2003).

당뇨병 백서의 간세포에서 Glucokinase 활성도 및 유전자 발현에 대한 인슐린의 영향

강성이,팽정령,서광식,안규정,우정택,김성운,양인명,김진우,김영설,김광원,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

목적 당대사의 조절 상태에 따른 생체 변화를 분자 수준에서 이해하고자 식이 조건을 달리한 정상 백서와 화학적으로 유도된 당뇨병 백서의 간조직에서 혈당수준과 인슐린치료 정도에 따라 나타나는 글루코키나제 활성도 및 유전자 발현을 분석하였다. 방법 스트렙토조토신 정맥투여 후 당뇨병의 유발을 확인하고, 인슐린을 1일 3회 3일간 복강내로 투여하여 상태를 안정시킨 후, 인슐린 투여군은 인슐린 투여 6시간이내에 그리고 인슐린 비투여군은 24시간 후 단두하여 채혈하고 복강을 열어 간조직을 채취하였다. 채취한 간조직에서 글루코키나제 활성도는 인산화된 포도당에서 NADH의 형성을 형광분광계로 측정하였으며, 글루코키나제 유전자 mRNA발현은 Northern 분석법을 이용하였다. 성적 정상 백서에서 공복상태와 식이를 섭취한 경우에 간조직의 글루코키나제 효소의 활성은 차이가 없었으나, 글루코키나제 유전자 mRNA 발현은 증가되었다. 당뇨병이 유발된 백서의 간조직에서 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA 발현은 정상 백서에 비하여 낮았다. 인슐린 투쳐 후 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA 발현이 증가되었고, 특히 혈당이 정상화된 경우에서 글루코키나제 유전자의 mRNA 발현이 증가도었다. 결론 인슐린에 의한 간조직에서 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA을 증가를 볼수 있었다. 당뇨병 백서에서 인슐린 투여 후에 혈당조절이 안된 경우 간조직의 글루코키나제 유전자의 mRNA 발현이 증가가 없는 것으로 보아 글루코키나제 mRNA의 발현에는 인슐린 이외의 다른 요소가 관여할 것으로 생각된다. The liver-specific hexokinase isoenzyme, referred to as glucokinase, is thought to play a key reglulatory role in hepatic glucose metabolism. The glucokinase gene is, therefore, of interest both because of its tissue-specific expression and because of the several regulatory processes that can be analyzed. The level of hepatic glucokinase activity appears to be determined essentially by regulation of the rate of enzyme synthesis, with insulin playing a leading role as an inducer. We investigated the role of insulin for the induction of glucokinase in the liver of diabetic rats. Experimental diabetes was induced by injection of streptozotocin 7 days before the experiment. Regular insulin was given by three days intraperitoneal injection at 8-h interval. The glucokinase mRNA in the liver was estimated by Nothern blot assay, as well as by fluorometric enzyme activity assay. Glucokinase activity was not reduced in the liver of normal fasting rats as compared to normal fed rats. And glucokinase activity was reduced in the liver of diabetic rats as compared to normal rats. In diabetic rats treated with insulin, glucokinase enzyme activity were increased. But glucokinase mRNA expression was only increased in normoglycemic diabetic rat with treated with insulin as compared to hyperglycemic rat. These data indicate that insulin stimulates hepatic glucokinase enzyme activity and mRNA expression. But other hormonal or metabolic factors may be contribute to regulation of glucokinase mRNA expression.

정상과 만성 염증성 활막배양세포에서 Cyclooxygenase mRNA 발현에 미치는 Corticotropin-Releasing Hormone(CRH)의 영향

정운원,윤기정,김유진,김병준,안규정,곽호윤,주영실,김응진 凡石學術奬學財團 2000 凡石學術論文集 Vol.4 No.-

혈당측정기 GlucoDr™ System의 평가

박철영,류미숙,우정택,김성운,김진우,김영설,안규정 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.2

연구배경: 당뇨병 환자에서 엄격한 혈당조절은 환자의 예후와 밀접한 관련이 있다. 혈당조절을 철저히 하기 위해서는 자가 혈당 측정기의 사용이 필수적이라 할 수 있다. 또한 저혈당이 빈번하게 발생하거나, 위험요소가 있는 환자들에게도 유용하게 사용될 수 있다. 이에 저자들은 전기화학감지법의 원리를 이용하여 국내에서 처음 생산된 자가혈당측정기인 GlucoDr™ blood Glucose Testing System(ALL Medicus, Co, Korea)를 현재 국내에서 시판되고 있는 다른 제품과 비교, 평가하여 임상적 유용성을 살펴보고자 하였다 방법: 혈당측정기준장비는 YSI 2300 STAT Plus(YSI Incorporated, USA)를 사용하였으며 GlucoDr™외에 Glucocard(KDK, Japan), Precision QID(Abbott Laboratories, Co, USA), Glucotrend(Roche, USA), Surestep(Lifescan, USA)의 다른 혈당측정기를 같이 평가하였다. 정밀도, 직선성, 비교방법과의 상관관계 평가, 검체량에 따른 영향, 헤마토크리트에 따른 영향, 검사자에 따른 영향, 항응고제에 따른 영향들을 평가하였다. 결과: 본 연구에서의 주된 평가대상인 GlucoDr™의 평가결과, 정밀도를 나타내는 검사 내, 검사 간 변이계수는 8%이내였으며, 45~500mg/dL 범위에서 R²=0.9906, 0.9984 정도의 직선성을 나타내었다. 본 연구에 있어 비교방법으로 이용한 YSI 2300 STAT Plus와의 상관관계 및 정확도는 y = 1.0058x + 0.453, R = 0.9853인 것으로 나타났다. 검체량이나 검사자 및 항응고제에 따른 측정값에는 유의할만한 차이가 없는 것으로 나타났으나, 헤마토크리트가 증가 또는 감소함에 따라 최소 10%에서 최대 26% 가량의 영향을 받는 것으로 관찰되었다. 결론: GlucoDrTM는 국내 사용되는 다른 혈당측정기와 비교하여 유용할 것으로 생각된다. Background: Self-monitoing blood glucose devices are sidely used in monitoring and point-of-care testing for the management of diabetic patients. We performed the present study to evaluate the performance of the GlucoDr™ blood glucose testing system using an electrochemical technique. Method: The GlucoDr™ was evaluated for linearity, precision, comparison of method, the effect of sample volume, hematocrit concentration, reapplication, operator and application methods. Results: The GlucoDr™ showed good linearity for glucose concentrations ranging from 52mg/dl to 475mg/dl(r²=0.971). The single day, and day-to-day, CV were within 8%. Excellent correlation was found between the GlucoDr™ and YSI 2300 STAT Plus(y=1.0058x + 0.453, r²=0.9710). The sample volume, reapplication, operator and application method produced no significant effect on the test result. An overestimation in the glucose values was found with low hematocrit concentrations. There was no significant effect by the anticoagulants, with the exception of citrate. Conclusion: The GlucoDr™ showed good linearity, precision and correlation with the reference method and provided rapid and reliable result for blood glucose levels. Therefore, the GlucoDr™ seems appropriate for clinical use in the management of diabetic patients.

저상선자극성 성선기능 저하증에서 복합뇌하수체 자극 시험에 의한 뇌하수체 전엽 호르몬의 동태

김진우,최영길,김영설,양인명,우정택,김성운,안규정,박은경 대한내분비학회 1994 Endocrinology and metabolism Vol.9 No.2

To classify the causes of hypogonadotropic hypogonadism in Korean patients, and to improve the endocrinologic evaluation for the disease, we retrospectively studied the clinical findings and result of combined pituitary stimulation test in 35 patients with hypogonadotropic hypogonadism. The following results were obtained. 1) The ratio of male to female was 1.3:1, and the 50% of male patients was under 20 years of age and the 20% of female patients in 30th decades. 2) The chief complaints of male patients on the admission were the failure of secondary sexual characteristics(95.0%) and loss of hair(5.0%), those of female patients were amenorrhea(46.7%), infertility(26.7%), failure of secondary characteristics(13.3%) and loss of hair(13.3%). 3) The causes of male hypogonadotropic hypogonadism were craniopharyngioma(35.0%), idiopathic(30.0%), Kallmann's syndrome(15.0%), pituitary adenoma(10.0%) and germinoma(5.0%), and those of female hypogonadotropic hypogonadism were prolactinoma(13.3%), Sheehan's syndrome(26.6%), pituitary adenoma(6.7%), tuberculous granuloma(6.7%), germinoma(6.7%), idiopathic hypogonadotropic hypogonadism(40.0%). 4) The responses of LH and FSH to GnRH test were absent or markedly blunted in diffuse pituitary diseases such as pituitary tuberculous granuloma, pituitary macroadenomas, Sheehan's syndrome. However those were also absent or blunted in Cushing's disease and hypothalamic disease such as Kallmann's syndrome, germinoma, craniopharyngioma, idiopathic hypogonadotropic hypogonadism. 5) The responses of LH, FSH increased after repeated injection of GnRH in a patient with germinoma. 6) In diffuse destructive pituitary diseases such as Sheehan's syndrome, nonfunctioning macroadenomas, tuberculous granuloma, large prolactinoma, the combined deficiency of pituitary hormones other than gonadotropins was observed. 7) In many cases with hypothalamic diseases, the combined defects of pituitary hormone response were also seen. These data suggest that GnRH test is not always useful to localize the lesion between pituitary and hypothalamus, and combined pituitary stimulation test revealed defects of pituitary hormones other than gonadotropin in various hypothalamic diseases. Therefore repeated GnRH test would be useful for the differential diagnosis, and CRH test and GRH test would be necessary to demonstrate whether pituitary abnormality is present. (J Kor Soc Endocrinol 9:93-107, 1994)

말단비대증을 동반한 뇌하수체 선종들의 면역조직화학적 및 임상적 특성의 비교

이명식,김성훈,김광원,민용기,고은미,정재훈,김경아,안규정,김병준,김진석,이문규,김종현,서연림,나동규 대한내분비학회 1998 Endocrinology and metabolism Vol.13 No.3

Background: It assumed that plurihormonal pituitary adenomas in acromegaly, which were immunohistochemically stained with other pituitary hormones in addition to GH and prolactin, would be originated from poorly differentiated cells. Therefore, we speculated that they might have higher growth rates and worse prognosis than monohormonal adenomas. To verify this speculation, we analyzed the frequency of plurihormonal adenomas and compared the clinical parameters and radiological invasiveness between plurihormonal adenoma and GH-prolactin adenoma in acromegaly. Methods: We studied 38 patients with acromegaly (22 males and 16 females, mean age 40.7 years) who were underwent surgical removal of pituitary adenomas by TSA from January 1995 to February 1998. We performed immunohistochemical staining in these tumors using avidinbiotin peroxidase complex method. An adenoma was considered as immunoreactive when above 50 percents of tumor cells were stained with anti-hormonal antibodies. Invasiveness of tumors were evaluated by preoperative MRI findings on the basis of Hardys classification. Results: The frequencies of plurihormonal and GH-prolactin adenomas were 42% and 58%, respectively. Plurihormonal adenoma included an adenoma which was not stained with prolactin, but with GH and other hormones. Prolactin immunoreactivity was found in 97%(37/38) of the tumors. Immunoreactivities to FSH, ACTH, LH, and TSH were found in 37.8%, 13.1%, 2.6% and 2.7%, respectively. There were no significant differences in age, basal serum GH and IGF-1 concentrations between plurihormonal and GH-prolactin adenomas. There were also no significant differences in response to TRH & LH stimulation tests and somatostatin & bromocriptine suppression tests between two groups. There were no differences in radiological invasiveness between two groups (plurihormonal adenoma, grade I 2, grade II 3, grade III 7, grade IV 4; GH-prolactin adenoma, grade I 3, grade II 6, grade III 9, grade IV 4). Conclusion: Plurihormonal adenomas were 44% and immunoreactivity to prolactin was 97% in pituitary adenomas in acromegaly. There were no significant differences in clinical parameters and radiological invasiveness between plurihormonal and GH-prolactin adenomas in acromegaly (J Kor Soc Endocrinol 13:324-330, 1998).