비소세포폐암에서 Microsatellite Instability

전효성,김정란,손지웅,박선하,박태인,김창호,김인산,정태훈,박재용 경북대학교 병원 2001 경북대학교병원의학연구소논문집 Vol.5 No.1

연구베경:MMR 유전자의 불활성화에 의해 야기되는 뮤전적 불안정성은 발암기전의 한 부류로 인정되고 있다.저자들은 비소세포폐암의 발암과정에서의 MSI의 역할을 규명하기 위해 비소세포폐암에서 MSI의 빈도 및 MSI 유무에 따른 임상상의 차이를 조사하였다. 대상 및 방법:근치적 절제술을 받은 비소세포폐암 20예를 대상으로 하였다.동결된 폐암조직과 환자의 림프구에서 DNA를 추출한 후 3P와 9p의 15개의 marker들을 대상으로 PCR을 시행하고 7% polyacrylamide gel에서 전기영동한 후 silver 염색을 시행하였다. 암조직과 림프구 DNA의 PCR product의 band를 비교하여 MSI와 LOH를 판정하였다. 결과:1)대상환자들은 남자 19예,여자 1예였으며 모두 흡연자였고 평균 흠연력은 47 갑년이었다. 폐암의 조직형은 편평상피암 15예, 선암 4예,대세포암 1예였고, 술 후 병리학적 병기는 Ⅰ기 6예,Ⅱ기 5예, ⅢA기 7예,ⅢB기 2예였다. 2)20예 가운데 8예(40%)에서 MSI가 관찰되었으며 3예는 한 개의 marker에서,5예는 2개 이상의 marker에서 MSI가 관찰되었다. 3)LOH는 10예(50%)에서 있었으며,LOH유무에 따른 병가 및 흡연력의 차이가 없었다. 4)분석한 marker의 10% 이상에서 MSI가 관찰된 MSI-L종양은 5예였으며, 대부분의 marker에서 MSI양성인 MSI-H종양은 없었다.MSS종양과 MSI-L종양은 흡연력, 병기, 폐암 조직형 및 LOH 빈도의 유의한 차이가 없었다. 결론:비소세포폐암에서 MSI는 비교적 흔히 관찰되지만 MMR 유전자의 불활성화에 의한 MMP pathway 는 비소세포폐암의 주요 발생기전은 아닐 것으로 생각된다.향 후 비소세포폐암의 발암과정에 있어서 MMP pathway의 역할을 규명하기 위해서는 보다 많은 예를 대상으로 한 연구가 필요할 것으로 생각되며, MSI 발생기전에 관한 추가적인 연구가 필요할 것으로 생각된다. Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype (MMP) tumors.MSI has been observed in a percentage of non-small cell lung cancer(NSCLC).However, its role in tumorigenesis of NSCLC remains unknown.The frequency and partten of MSI in NSCLC were evaluted and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p.The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results:1) of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats that in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LOH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors( showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and (delete) stage of disease.There was also no significant difference in the incidence of LOH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer.MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.(tuberculosis and Respiratory Diseases 2000,48:24-32)

일제강점기 초등교육의 본질 : 교육과정 요소를 중심으로 Goals and Objectives, Contents, Teaching Methods, and Evaluations

김경자,김민경,김인전,이경진,김유진 한국초등교육학회 2004 초등교육연구 Vol.17 No.1

이 연구에서는 초등교육의 본질을 탐색하기 위하여 일제강점기 초등교육에 대한 탐구를 하였다. 구체적으로 이 연구에서는 일제 강점기 교육제도, 교육목표, 교과 및 교육내용, 교육방법, 평가, 교원양성 등에 나타난 특수성을 탐구하고, 4차에 걸친 조선교육령 시기에 나타나는 규칙적인 현상을 밝혀보았다. 그리고 연구 결과는 이 연구에서 잠정적으로 전제한 공교육의 이상과 초등교육의 일반성과 관련지어 해석되었고, 이는 다시 현재 진행되고 있는 7차 초등교육과정과 관련하여 어떤 것이 지속되고, 어떤 것이 변화되었는지에 대한 논의로 전개되었다. 가능한 광범위하게 수집한 1차적 사료와 2차적 사료를 교육에 대한 관점별로 범주화하고 연구에서 다루고자 하는 요소별로 정리를 하였다. 필요한 경우, 직접 일제강점기 초등교육을 경험한 사람들을 면접하였다. 연구결과, 일제강점기 초등교육의 목표는 기형적인 "국민"을 길러내는 것이었으며, 이러한 목표를 달성하기 위한 교육내용, 교육방법, 교육평가는 기능적 측면에서 "잘", 효율적으로 기능할 수 있도륵 일관성을 유지하고 있는 것으로 나타났다. 이는 교육적일 수 없는 모순을 내재한 것이 된다. 따라서 일제강점기 초등교육에서 초등교육의 본질을 찾기가 어렵다는 결론을 내릴 수 있다. This research aims to seek the real nature of elementary education by investigating the system in Korea under the rule of Japanese imperialism (1909-1945). Special characteristics are identified in their goals and objectives, contents, teaching methods, and evaluations in elementary education system during the period. Futhermore, some regular phenomena are traced out during the four-time amendments of education rules in the law. Firstly, the results of this study are described in the viewpoint of the ideals in public education, which are tentatively proposed by our authors. Secondly, they are compared and contrasted to the 7th Amended National Curriculum of Korea in terms of the perspectives of curriculum. Some parts in the research are supported by the interviewees who had experienced in the elementary education during the imperialistic period. The result suggests that the system in the colonized period was conducted to cultivate the students who were inappropriate in compared with our ideals in the education. For the goals, the elements of the system in the above were consistently maintained and functionally well-carried out. Therefore, the system was not evaluated as educative intrinsically. Henceforth, the real nature of elementry education would not be drawn in the system during the rule in conclusion.

보건소를 이용하는 지역주민의 건강 행위와 건강관련 체력간의 관계

전미양,최명애,이인숙,김태수,김의숙,박선홍 대한보건협회 2002 대한보건연구 Vol.28 No.3

The purpose of this study is to identify relationship health behavior and health related physical fitness in order to provide the basic data for health promotion program for community people. The study was conducted 299 people, during the period from June 1, 2000 to October 30, 2000. The result are as follows. 1. Female comprised was 63.2%(189), while male comprised 36.8%(110). The age range of the subject were from 21 to 59 years old. The subject were aged 30s group 52.5%, 40s group 29.1%, 50s group 12.7%, 20s group 5.7%. Twenty subjects (6.7%) had experience smoking and one subject (0.3%) in female and nineteen subjects (6.4%) in male. Seventy-five subjects (25.1%) had experience drinking and twenty-nine subjects (9.7%) in female, and forty-six (15.4%) in male subjects. ninety-nine subjects had exercise and sixty subjects (20.1%) in female subjects and thirty-mine subject (13%) in male. 2. Body fat and flexibility were higher in female than male subjects, but cardioresperatory endurance, muscular strength and muscular endurance were higher in male than female subjects. 3. There were significant differences in body fat and muscular endurance between age group in both gender subjects, and in cardioresperatory endurance and muscular strength between the age group in male subjects. 4. No significant differences health related fitness between non-smoking and smoking group in both gender subjects. 5. No significant differences health related fitness between non-alcohol and alcohol group in both gender subjects. 6. For female subjects, muscular strength, muscular endurance and flexibility of the exercise group were significantly higher than those of the non exercise group. for male subjects, cardiorespiratory endurance of the exercise group were significantly higher than those of the non exercise group.

Test of the ITER-like resonant magnetic perturbation configurations for edge-localized mode crash suppression on KSTAR

In, Yongkyoon,Loarte, A.,Lee, H.H.,Kim, K.,Jeon, Y.M.,Park, J.-K.,Ahn, J.-W.,Park, G.Y.,Kim, M.,Park, H. International Atomic Energy Agency 2019 Nuclear fusion Vol.59 No.12

<P>KSTAR has demonstrated divertor heat flux broadening during edge-localized mode (ELM) crash suppression using ITER-like three-row resonant magnetic perturbation (RMP) for the first time. To address a couple of critical issues in ITER RMP, robust ELM-crash-suppression methodology has been explored at low <I>q</I> <SUB>95</SUB> and established in KSTAR using low-<I>n</I> RMPs. Taking full advantage of the ITER-like three-row in-vessel control coils (IVCC) in KSTAR, a set of intentionally misaligned RMP configurations (IMC) was tested to investigate whether or not IMC could be compatible with ELM crash suppression, while minimizing electromagnetic loads on RMP coils. As a result, the ITER-like three-row IMCs were found not only to have been compatible with the ELM crash suppression, but also to have broadened the divertor heat fluxes in the vicinity of the outer strike point. In comparison, the two-row RMPs have rarely affected the near scrape-off layer (SOL) heat flux despite slightly broadened profile change in the far-SOL. Since the divertor heat flux broadening reflects the dispersal of the peaked near-SOL heat flux, the experimental outcome is quite favorable to the ITER choice of three rows, instead of two rows. Nonetheless, since the IMC-driven broadening observed in the attached plasmas in KSTAR might appear substantially different in the partially detached plasmas in ITER, additional investigation has been conducted to see if RMP-driven, ELM crash suppression could be compatible with detached plasmas. Although no detached plasmas have been identified with ELM crash suppression yet, significantly reduced divertor heat flux was confirmed in high density, ELM-crash-suppressed plasmas at <I>q</I> <SUB>95</SUB>  =  3.4 using <I>n</I>  =  2 RMPs. These new findings elevate the confidence level about the ITER RMP system, while the remaining uncertainties need to be further clarified using the three-row IVCCs in KSTAR.</P>

관상동맥 스텐트 시술 후의 재협착에 관한 연구

김윤철,이정우,김보영,강정아,임대승,이민수,김정희,성보영,최성준,성인환,전은석 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.1

Coronary stent implacement is known as an effective treatment in the intimal dissection after percutaneous transluminal coronary angioplasty and the prevention of restenosis. However, In-stent restenosis still remains a major concern in clinical stenting. The stents were placed in 103 patients from July 1996 to March 1999 and performed follow-up coronary angiograms in 59(57.3%) patients. To identify the clinical, angiographic and procedurerelated variables 'which predict late restenosis within the stented artery, 59 patients(58.3±9.9, M:F= 41:18) were studied. The clinical characteristics of the patients were stable angina in 23(39.0%), unstable angina in 14(23.7%), acute myocardial infarction in 21(35.6%) and old myocardial infarction in 1(1.7%). Coronary stenting was performed in 1 patient(1.7%) for primary lesion, 50 patients(84.7%) for suboptimal results after PTCA, 6 patients(10.2%) for bail-out procedure, and 2 patients(3.4%) for restenotic lesions. All patients were treated with aspirin and ticlopidinc. The follow-up angiograms were obtained at 7±4 months. The overall in-stent restenosis rate was 27.1%. The coronary angiographic findings were 32 single vessel(54.2%), 19 two vessel(32.2%) and 8 three vessel disease(13.6%). The angiographic morphological characteristics were type A in 33(55.9%), type B in 14(23.7%), type C in 12(20. 3%) cases. Variables of 16 patients with restenosis were compared with those of 43 patients without restenosis. Previously known predictors for in-stent restenosis were multiple stenting, stenting for restenotic lesions, residual stenosis after stenting, stenting for total occlusion lesions, reference diameter, balloon to vessel ratio, acute gain and minimal luminal diameter after procedure, design and characteristics of stents, ostial lesion of aorta, high pressure method for stenting, lesion length, diabetes mellitus, size of artheroma, saphenous vein grafts, ulcerlating lesions and calcified lesions. In this study, Reference diameter before stenting(2.43±0.54mm vs. 2.88±0.65mm, p=0.016) and balloon-to-artery ratio(1.28±0.26 vs. 1.11±0.18, p=0.006) were predictors for in-stent restenosis. 1) The overall in-stent restenosis rate was 27.1%. 2) In the analysis of predictors for in-stent restenosis, there was no significant differences in clinical, angiographic factors between group with restenosis and without restenosis. But, Only reference diameter before stenting and balloon-toartery ratio were predictors of late in-stent restenosis. In conclusion, stenting is effective revascularisation method for selected patients with ischemic heart disease, and to minimize in-stent restenosis rate, stent implanting is achieved in a large vessel on the basis of an artery-to-stnet ration of 1:1, if possible.

In-direct localized surface plasmon resonance (LSPR)-based nanosensors for highly sensitive and rapid detection of cortisol

Jeon, Jinwoo,Uthaman, Saji,Lee, Jiyoung,Hwang, Hyejin,Kim, Gibum,Yoo, Pil J.,Hammock, Bruce D.,Kim, Christine S.,Park, Yeon-Su,Park, In-Kyu Elsevier 2018 Sensors and actuators. B, Chemical Vol.266 No.-

<P><B>Abstract</B></P> <P>Over-secretion of cortisol from the adrenal cortex is closely related to acute and chronic stress; thus, rapid and sensitive detection of cortisol in serum is of critical importance for preventing the progression of stress-related diseases. The binding of a biological molecule to the surface of metallic nanoparticles changes the local refractive index and in turn induces a shift in the localized surface plasmon resonance (LSPR) wavelength. Utilizing this phenomenon, we designed a novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. The developed cuvette-type nanosensor consists primarily of an assembly of plastic unit sensors coated with gold nanoparticles on a single layer wherein cortisol-conjugated bovine serum albumin (BSA) is immobilized. In this system, a redshift in LSPR wavelength is induced by the binding of cortisol antibody onto cortisol-conjugated BSA immobilized on a gold nanoparticle surface in the nanosensor. In a competitive assay, the nanosensor could rapidly detect cortisol in both a PBS solution and serum (within 20 min) at concentrations ranging from 1 to 10,000 ng/mL (2.759–3 × 10<SUP>3</SUP> nmol/L), which is comparable to conventional enzyme-linked immunosorbent assay (ELISA) which typically requires longer than 4 h and complex sample preparation. Thus, we demonstrated that the LSPR-based nanosensor system developed in this study can provide a useful toolkit for a rapid, highly sensitive and reliable detection of cortisol hormone in a commercially available manner.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. </LI> <LI> Rapid, convenient, and sensitive method for detecting cortisol hormone in serum. </LI> <LI> Detect cortisol in both PBS solution and serum within 20 min at concentrations ranging from 1 to 10,000 ng/mL. </LI> </UL> </P>

Trend of Intensive Care Unit Admission in Neurology- Neurosurgery Adult Patients in South Korea : A Nationwide Population-Based Cohort Study

Saeyeon Kim,Tak Kyu Oh,In-Ae Song,Young-Tae Jeon 대한신경외과학회 2024 Journal of Korean neurosurgical society Vol.67 No.1

Objective : We aimed to examine trends in critically ill neurology-neurosurgery (NNS) patients who were admitted to the intensive care unit (ICU) in South Korea and identify risk factors for in-hospital mortality after ICU admission in NNS patients. Methods : This nationwide population-based retrospective cohort study enrolled adult NNS adult patients admitted to the ICU from 2010 to 2019 extracted from the National Health Insurance Service in South Korea. The critically ill NNS patients were defined as those whose main admission departments were neurology or neurosurgery at ICU admission. The number of ICU admission, age, and total cost for hospitalization from 2010 to 2019 in critically ill NNS patients were examined as trend information. Moreover, multivariable logistic regression modeling was used to identify risk factors for in-hospital mortality among critically ill NNS patients. Results : We included 845474 ICU admission cases for 679376 critically ill NNS patients in South Korea between January 1, 2010 to December 31, 2019. The total number of ICU admissions among NNS patients was 79522 in 2010, which increased to 91502 in 2019. The mean age rose from 62.8 years (standard deviation [SD], 15.6) in 2010 to 66.6 years (SD, 15.2) in 2019, and the average total cost for hospitalization per each patient consistently increased from 6206.1 USD (SD, 5218.5) in 2010 to 10745.4 USD (SD, 10917.4) in 2019. In-hospital mortality occurred in 75455 patients (8.9%). Risk factors strongly associated with increased in-hospital mortality were the usage of mechanical ventilator (adjusted odds ratio [aOR], 19.83; 95% confidence interval [CI], 19.42–20.26; p<0.001), extracorporeal membrane oxygenation (aOR, 3.49; 95% CI, 2.42–5.02; p<0.001), and continuous renal replacement therapy (aOR, 6.47; 95% CI, 6.02–6.96; p<0.001). In addition, direct admission to ICU from the emergency room (aOR, 1.38; 95% CI, 1.36–1.41; p<0.001) and brain cancer as the main diagnosis (aOR, 1.30; 95% CI, 1.22–1.39; p<0.001) are also potential risk factors for increased in-hospital mortality. Conclusion : In South Korea, the number of ICU admissions increased among critically ill NNS patients from 2010 to 2019. The average age and total costs for hospitalization also increased. Some potential risk factors are found to increase in-hospital mortality among critically ill NNS patients.

경추전방 유합술 후 인접분절의 변화

박희전,김인구,김완기 대한척추외과학회 2003 대한척추외과학회지 Vol.10 No.3

한국 일 도시지역 청소년의 우울 증상 유병률과 관련요인에 대한 연구

조성진,전홍진,김무진,김장규,김선욱,류인균,조맹제 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구 목적 : 한국의 일 도시지역에 거주하는 청소년의 우울 증상의 유병률과 관련요인을 밝힘으로써 청소년 정신건강 증진을 위한 기초 자료를 수집하기 위하여 실시되었다. 방 법 : 연구 대상은 부천시에 거주하는 중학교나 고등학교에 재학중인 청소년 71,102명 가운데에서 무작위 집락 표본 추출법에 의해 선정된 2,203명이었으며, 이들에 대해서 CES-D(the Center for Epidemiologic Studies Depression Scale)와 사회인구학적 정보에 대한 문항이 들어 있는 설문을 실시하였다. 설문은 직접 학교를 방문하여 수행하였다. 선정된 2,203명의 청소년 가운데에 CES-D문항을 완성한 학생은 1,972명으로 반응률은 89.5%였다. 결 과 : 1) CES-D의 절단점을 16점으로 하여 계산한 '가능한' 우울 증상의 유병률은 중학생의 경우에 남학생 34.6%, 여학생 44.7%였으며, 고등학생의 경우에는 남학생 43.8%, 여학생 49.6%였다. 2) CES-D의 절단점을 25점으로 하여 계산한 '명확한' 우울증 증상의 유별률은 중학생의 경우에 남학생 18.4%, 여학생 20.7%였으며, 고등학생의 경우에는 남학생 21.4%, 여학생 23.9%였다. 3)종교, 인문계와 실업계의 여부에 따라서 우울 증상의 유병률에는 유의한 차이가 없었다. 4) 성,학년, 생활수준에 대한 자신의 평가, 가족의 구조, 성적에 대한 만족도의 다섯 가지 변수에 대해 CES-D점수가 16점 이상인 우울 증상의 유무에 따라서 로지스틱 회귀 분석을 시행하였을 때 성적에 대해 불만적 하는 군에서 매우 만족하는 군에 비해서 8.850배의 상대 위험도를 보였다. 생활 수준을 중하정도라고 대답한 군은 상이라고 대답한 군에 비해서 2.007배의 상대 위험도를 보였다. 여학생은 남학생에 비해서 1.307배의 상대 위험도를 보였다. 5) 우울 증상에 있어서 남학생과 여학생의 비율은 전체 군에서 1:1.38이며 중학생의 경우에는 1:1.88, 고등학생의 경우에는 1:1.13으로 나타났다. 고등학생에 있어 남학생의 우울 증상이 증가하는 것은 학업과 입시에 대한 부담과 관련된 것으로 생각되었다. 결 론 : 한국 일 도시거주 중고등학생에서 CES-D로 측정한 우울 증상은 남학생의 34.3%, 여학생의 47.5%에서 나타날 정도로 흔하다. 특히 학업 성적에 대해 불만족 하는 군에서 높은 우울 증상의 상대 위험률을 보이며, 고등학생에서 남학생의 우울증의 유병률이 높아지는 것은 이 지역 학생들이 학업에 대한 높은 부담을 가지고 있다는 것을 알 수 있었다. 따라서 이들에 대한 특별한 관심이 요구된다. Objective : We tried to see the prevalence and correlates of symptoms of depression in an adolescent population in Korea, and collected the basal data for mental health promotion of adolescents. Method : We sampled 2,203 adolescents among 71,102 adolescents living in Puchon City in Korea by the randomized clustered sampling method. The Center for Epidemiologic Studies Depression scale(CES-D) was used to measure depressive symptoms. The measurements were conducted through visiting schools. Of the 2,203 adolescents(aged 13 to 18) who were sampled, 1,972 persons completed CES-D and sociodemographic questions. The response rate was 89.5%. Result : 1) The prevalence rate of 'probable' depressive symptoms with cutoff point 16 was 34.3% in the boys and 47.5% in the girls. 2) The prevalence rate of 'definite' depression symptoms with cutoff point 25 was 17.4% in the boys and 20.6% in the girls. 3) We could not find any meaningful difference in the average of CES-D from the districts where they live, the course of their education, and their religions. 4) We used the logistic regression analysis to find the risk factor for adolescent depression in these samples. Among the variables degree, it was most important risk factor in adolescent depression to dissatisfy with their school degrees. Compared it with fully satisfied group, the odds ratio was 8.850. The group of mid to low socioeconomic status had the odds ratio 2.007 compared with high socioeconomic status. The girls had the odds ratio 1.307 compared with the boys. 5) The male versus female ratio was 1: 1.38 in the total students and 1 : 1.88 in the middle school students, and 1 : 1.13 in the high school students. The male versus female ratio was relatively low in the high school students. It was the result of the high prevalence of depressive symptoms in the high school boys, and it was due to the large burden to their school degrees. Conclusion : The depressive symptoms checked by CES-D were very common among adolescents in Korean urban area. The prevalence of depressive symptoms was 34.3% in the boys and 47.5% in the girls. The result that male versus female ratio was relatively low in the high school adolescents, and the group that were dissatisfied with the school degrees had high risk of depressive symptoms, revealed that the students had large burden to their school degrees and so they needed special concerns.

LETTER TO THE EDITOR : Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with abnormal cortisol secretion mediated by catecholamines

( Harin Rhee ),( Yun Kyung Jeon ),( Sang Soo Kim ),( Yang Ho Kang ),( Seok Man Son ),( Yong Ki Kim ),( In Joo Kim ) 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.5

Adrenocorticotropic hormone (ACTH)- independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing syndrome. In AIMAH, cortisol secretion is independent of ACTH, and various hormones and/or cytokines have been thought to stimulate cortisol secretion via the aberrant expression of adrenal receptors or the increased activity of eutopic hormone receptors. Schorr and Ney [1] f irst proposed this concept, and subsequently the ectopic expression of gastric inhibitory peptide (GIP), V2 and V3-vasopressin, β -adrenergic, luteinizing hormone (LH)/human chorionic gonadotropin (hCG), serotonin, and angiotensin receptors, as well as increased activity of a eutopic V1-vasopressin receptor, have been identified in the adrenal gland [1,2]. Several genetic factors, such as Gs α-subunit mutations associated with McCune-Albright syndrome and MC2R (ACTH receptor gene) mutations, have also been postulated as causes of AIMAH. A 50-year-old male was referred and admitted to our hospital due to uncontrolled hypertension. He had suffered from hypertension for 6 years. His blood pressure was originally well controlled for the first 5 years using a calcium channel blocker, but poorly controlled for 1 year before he visited our hospital, despite his regular use of antihypertensive agents. He was initially referred to the Cardiology Department and underwent cardiologic evaluation after complaining of paroxysmal palpitation and dizziness. His 24-hour Holter monitoring and coronary angiographic results were normal, except for several antigen- presenting cells and a minimal coronary arterial obstruction at the middle left anterior descending artery. He had a past history of major depression and had been prescribed an antidepressive agent 18 months before he visited our hospital. On physical examination, he had a moon face, marked central obesity (height, 167 cm; weight, 77.65 kg; body mass index, 27.84 kg/m2), and multiple bruises on his extremities. He also had prominent purple abdominal striae, and all of his morphological features were consistent with Cushing syndrome. Laboratory examinations revealed 145.7 mEq/L serum sodium and 2.86 mEq/L serum potassium. Arterial blood gas analysis revealed metabolic alkalosis (pH 7.519, HCO3, 37.4 mM/L). His hemoglobin A1c level was 5.9%, and his serum fasting blood glucose was 118 mg/dL. The results of basal endocrinological examinations are summarized in Table 1. The circadian variation in serum cortisol production was disrupted, and basal ACTH levels were suppressed. A 24-hour urinary free cortisol test and overnight dexamethasone suppression test (DMST) were both suggestive of Cushing syndrome. Low- and high-dose DMST revealed Cushing syndrome of primary adrenal origin. An abdominal computed tomography scan and magnetic resonance imaging (MRI) revealed bilateral large macronodular adrenal tumors. His pituitary gland was normal on brain MRI scans. We thus diagnosed this patient with Cushing syndrome secondary to AIMAH. To identify aberrant receptors on the adrenal gland, we followed the investigative protocol described by Lacroix et al. [3]. Postural and various provocation tests, including ACTH (250 μg, intravascular), arginine vasopressin (AVP; 10 IU, intramuscular), 5-hydroxy triptamine (5-HT; 10 mg, intravascular), isoproterenol (20 ng/kg/min, intravascular for 30 minutes) and mixed meal tests, were performed. His serum cortisol level showed a positive response to ACTH, AVP, and isoproterenol provocation tests, but a negative response to the postural stimulation test. The results are summarized in Fig. 1A. If the patient had β-adrenergic or AVP receptors on his adrenal gland, then he would have responded to the postural stimulation test; but he did not. We repeated the postural stimulation test, and checked his endogenous antidiuretic hormone (ADH) level. He exhibited an increased ADH level on the postural test, but no cortisol secretion (Fig. 1B). A bilateral adrenalectomy was performed. The subsequent pathological examination of both adrenal glands showed hyperplasia with a multinodular growth pattern: the right and left adrenal glands were sized 14.0 × 5.0 × 3.0 cm and 9.0 × 5.0 × 3.0 cm, respectively, and multiple golden yellow nodules measuring up to 4 cm in diameter were present. Microscopic findings showed that the nodules consisted of variable- sized nests of lipid-laden clear cells similar to those of the normal fasiculata layer (Fig. 2). The final clinical and pathological diagnosis was Cushing syndrome secondary to β-adrenergic agonist-responding AIMAH. After the operation, he took physiological doses of prednisolone and f ludrocortisone. He then lost weight gradually and achieved optimal blood pressure with reduced doses of antihypertensive agents. Kirschner et al. [4] first described AIMAH in 1964. They demonstrated that hypercortisolism was ACTH-independent, and that the resected adrenal glands contained multiple nodules. Since then, a number of cases have been described, and the cause of AIMAH has been characterized more precisely. Previously, steroid production in AIMAH was believed to be autonomous. In the previous study that compared the adrenal glands of patients with AIMAH to those in patients with long-standing Cushing disease, and concluded that prolonged adrenal stimulation by ACTH resulted in adrenal bilateral nodular formation and varying ranges of adrenal autonomy [5]. There were also some cases in which autonomy of the adrenal gland was the result of chronic ACTH stimulation, which eventually resulted in ACTH suppression. However, the rarity of Nelson syndrome following bilateral adrenalectomy in patients with AIMAH strongly argued against the adrenal autonomy hypothesis. In 1971, Schorr and Ney [1] first introduced the concept of aberrant adrenal receptor expression in adrenocortical tissue. They performed in vitro studies, and found that cyclic adenosine monophosphate and corticosterone production in rat adrenocortical carcinoma cells were stimulated by non-ACTH hormones such as catecholamines, thyroid stimulating hormone, follicle stimulating hormone, LH, and prostaglandin E1. This hypothesis was later validated in humans by additional in vitro and in vivo studies. Several ectopic receptors such as GIP, β-adrenergic receptors, vasopressin (V2-V3-vasopressin receptor), serotonin (5-HT7 receptors), and angiotensin II receptors, and increased expression or altered activity of eutopic receptors in- cluding the V1-vasopressin receptors, LH/hCG receptors, serotonin (5-HT4 receptor), and leptin receptors was found [5]. In our patient, the serum cortisol level was increased by ACTH stimulation, exogenous AVP, and isoproterenol. Because exogenous AVP could naturally stimulate ACTH and increase serum cortisol levels, we checked serum ACTH levels during an AVP stimulation test. His serum cortisol level was increased by 82%, and serum ACTH level was increased by 11.5%. We were unable to confirm if AVP itself stimulated the adrenal cortex directly, or whether the induced ACTH caused cortisol secretion. A postural test was performed to screen for the aberrant expression of the AVP, β-adrenergic, or angiotensin II receptors. Interestingly, cortisol secretion was stimulated by exogenous AVP and a β-adrenergic agonist; however, a postural test failed to stimulate cortisol secretion. We repeated the postural test, and also checked the patient`s aldosterone level to verify if the test was accurate and determined serum ADH levels to confirm if endogenous ADH stimulated adrenal cortisol secretion. Because serum aldosterone levels increase in response to postural stimulation, the test itself was working; however, the cortisol response was negative. This suggests that the patient`s β-adrenergic receptor showed a blunted response to the test. Because we did not determine the serum catecholamine levels during postural stimulation, it was unclear whether the postural test induced sufficient endogenous catecholamine. Although a stronger stimulus (such as a treadmill test) would have induced endogenous catecholamine and increased serum cortisol levels, the patient refused because he had ischemic heart disease. In our case, exogenous AVP, but not endogenous ADH, stimulated adrenal cortisol secretion. This suggests that the cortisol response to exogenous pharmacological levels of vasopressin was mediated by AVP-induced catecholamine release [3]. We finally concluded that this patient had ectopic β-adrenergic receptors on the adrenal cortex, and recommended long-term propranolol therapy. However, because he strongly desired to undergo treatment with a rapid response, we consulted the Urological Department who recommended bilateral adrenalectomy. The identification of aberrant adrenal hormone receptors in AIMAH provides novel opportunities for specific pharmacological therapies as alternatives to adrenalectomy. In 1997, Lacroix et al. [3] reported the use of propranolol therapy for ectopic β-adrenergic receptors in adrenal Cushing syndrome in 1997. Some studies have revealed aberrant receptor expression in vitro using reverse transcription polymerase chain reaction. However, a limitation of our study is that we did not confirm aberrant receptor expression using in vitro analyses. In conclusion, we report a rare case of an AIMAH patient. In vivo examinations suggested that altered cortisol regulation due to a β-adrenergic agonist was involved in the pathogenesis of the AIMAH patient.