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.

Low serum bilirubin level predicts the develop-ment of chronic kidney disease in patients with type 2 diabetes mellitus

( Kang Hee Ahn ),( Sang Soo Kim ),( Won Jin Kim ),( Jong Ho Kim ),( Yun Jeong Nam ),( Su Bin Park ),( Yun Kyung Jeon ),( Bo Hyun Kim ),( In Joo Kim ),( Yong Ki Kim ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.5

Background/Aims: We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T₂DM). Methods: This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of₃₄₉ patients with T₂DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. Results: The group with the lowest range of total serum bilirubin level (Q₁) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q₁ vs. Q₄; hazard ratio [HR], 6.75; 95% confidence in-terval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bili-rubin level than that in the highest quartile of the serum bilirubin level (Q₂ vs. Q₄; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). Conclusions: Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T₂DM and preserved renal function.

순산소 순환유동층에서 로내 탈황 및 탈질법 적용에 따른 오염물질 거동특성

최경구(Gyung-Goo Choi),나건수(Geon-Soo Na),신지훈(Ji-Hoon Shin),길상인(Sang-In Keel),이정규(Jung-Kyu Lee),허필우(Pil-Woo Heo),윤진한(Jin-Han Yun) 한국청정기술학회 2018 청정기술 Vol.24 No.3

순산소 연소기술은 화력발전에 적용 가능한 유망한 온실가스 감축 기술로 평가되고 있다. 본 연구는 환경적 관점에서 순환유동층을 활용한 순산소 연소조건에 로 내 탈황 및 탈질법을 적용하여 NO 및 SO₂의 거동을 살펴보는 한편, SO₃, NH₃, 그리고 N2O의 발생 경향도 관측하였다. 이를 위해, 연소로 내 석회석 및 요소수를 투입하였다. 로 내 탈황법은 연소가스 내 SO₂ 농도를 ~403에서 ~41 ppm까지 저감하였다. 또한 SO₃ 형성의 주원료인 SO₂가 저감되면서 연소가스 내 SO₃ 농도도 ~3.9에서~1.4 ppm까지 감소되었다. 그러나 석회석 내 CaCO₃가 NO의 발생을 촉진하는 현상도 관측되었다. 연소가스 내 NO 농도는로 내 탈질법을 적용하여 ~26 - 34 ppm까지 저감되었다. 요소수 투입량 증가에 따라 연소가스 내 NH₃ 농도가 증가하여 최대~1.8 ppm으로 나타났으며, N₂O의 농도도 ~61에서 ~156 ppm까지 증가하였다. N₂O 발생량 증가 현상은 요소수의 열분해 과정에서 생성된 HNCO가 N₂O로 전환되어 나타난다. 본 연구의 결과를 통해 로 내 연소가스 세정법을 적용할 경우 NOx 및 SOx의 저감뿐만 아니라, 다른 오염물질의 발생에 대한 주의가 필요할 것으로 보인다. Oxy-fuel combustion is considered as a promising greenhouse gas reduction technology in power plant. In this study, the behaviors of NO and SO₂ were investigated under the condition that in-furnace deNOx and deSOx methods are applied in oxy-fuel circulating fluidized bed combustion condition. In addition, the generation trends of SO₃, NH₃ and N2O were observed. For the purpose, limestone and urea solution were directly injected into the circulating fluidized bed combustor. The in-furnace deSOx method using limestone could reduce the SO₂ concentration in exhaust gas from ~403 to ~41 ppm. At the same experimental condition, the SO₃ concentration in exhaust gas was also reduced from ~3.9 to ~1.4 ppm. This trend is mainly due to the reduction of SO₂. The SO₂ is the main source of the formation of SO₃. The negative effect of CaCO₃ in limestone, however, was also appeared that it promotes the NO generation. The NO concentration in exhaust gas reduced to ~26 - 34 ppm by appling selective non-catalytic reduction method using urea solution. The NH₃ concentration in exhaust gas was appeared up to ~1.8 ppm during injection of urea solution. At the same time, the N₂O generation also increased with increase of urea solution injection. It seems that the HNCO generated from pyrolysis of urea converted into N₂O in combustion atmosphere. From the results in this study, the generation of other pollutants should be checked as the in-furnace deNOx and deSOx methods are applied.

Barium Hexaferrite Thin Films Prepared by the Sol - Gel Method

Sung Yong An,Sang Won Lee,In-Bo Shim,Sung-Roe Yun,Chul Sung Kim 한국자기학회 2001 Journal of Magnetics Vol.6 No.1

Nano-crystalline hexaferrite BaFe₁₂O_(19) (BaM) thin films have been prepared by the sol-gel method. A solution of Ba-nitrate and Fe-nitrates was dissolved in solvent with the stoichiometric ratio Ba/Fe=1/10. Films were spin-coated onto SiO₂/Si substrates, dried and then heated in air at various temperatures. In films prepared at a drying temperature Td=250 ℃ and a crystallizing temperature 650 ℃, single-phase BaM was obtained. High coercivities were obtained in these nano-crystalline thin films, 4~5.5 kOe for hexaferrite. Polycrystalline BaM/SiO₂/Si(100) thin films were characterized by Rutherford backscattering (RBS), thermogravimetry (TGA), differential thermal analysis (DTA), x-ray diffraction (XRD), and vibrating sample magnetometry (VSM), as well as Fourier transform infrared spectroscopy (FTIR). The perpendicular coercivity H_(c⊥) and in-plane coercivity H_(CII) after annealing at 650 ℃ for 2 hours were 4766 Oe and 4480 Oe, respectively, at room temperature, under a maximum applied field of 10 kOe.

Ultrasensitive and selective C₂H₅OH sensors using Rh-loaded In₂O₃ hollow spheres

Kim, Sun-Jung,Hwang, In-Sung,Na, Chan Woong,Kim, Il-Doo,Kang, Yun Chan,Lee, Jong-Heun Royal Society of Chemistry 2011 Journal of materials chemistry Vol.21 No.46

<P>Rh-loaded In<SUB>2</SUB>O<SUB>3</SUB> hollow spheres with diameters of ∼2 μm were prepared by a one-pot hydrothermal reaction of aqueous solution containing indium nitrate, rhodium chloride, and glucose and subsequent heat treatment at 500 °C for 2 h. The response to 100 ppm C<SUB>2</SUB>H<SUB>5</SUB>OH (<I>R</I><SUB>a</SUB><I>/R</I><SUB>g</SUB>, <I>R</I><SUB>a</SUB>: resistance in air, <I>R</I><SUB>g</SUB>: resistance in gas) of 1.67 at% Rh-loaded In<SUB>2</SUB>O<SUB>3</SUB> hollow spheres was 4748, which was ∼180 times higher than that of pure In<SUB>2</SUB>O<SUB>3</SUB> hollow spheres. Rh loading decreased the temperature for maximum gas response from 475 °C to 371 °C, which also enhanced the selectivity to C<SUB>2</SUB>H<SUB>5</SUB>OH 15.1–24.7 times and recovery speed. The ultrahigh sensitivity and selectivity to C<SUB>2</SUB>H<SUB>5</SUB>OH, the lower sensing temperature, and the reduced recovery time were attributed to electronic interactions between Rh and In<SUB>2</SUB>O<SUB>3</SUB> and the promotion of catalytic dissociation of C<SUB>2</SUB>H<SUB>5</SUB>OH into reactive gases.</P> <P>Graphic Abstract</P><P>The Rh-loaded In<SUB>2</SUB>O<SUB>3</SUB> hollow spheres with ultrahigh response and selectivity to C<SUB>2</SUB>H<SUB>5</SUB>OH were prepared by glucose-mediated, one-pot hydrothermal reaction and subsequent removal of core carbon by heat treatment. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1jm14252f'> </P>

Analysis on RF parameters of nanoscale tunneling field-effect transistor based on InAs/InGaAs/InP heterojunctions.

Woo, Sung Yun,Yoon, Young Jun,Cho, Seongjae,Lee, Jung-Hee,Kang, In Man American Scientific Publishers 2013 Journal of Nanoscience and Nanotechnology Vol.13 No.12

<P>Tunneling field-effect transistors (TFETs) based on the quantum mechanical band-to-band tunneling (BTBT) have advantages such as low off-current and subthreshold swing (S) below 60 mV/dec at room temperature. For these reasons, TFETs are considered as promising devices for low standby power (LSTP) applications. On the other hand, silicon (Si)-based TFETs have a drawback in low on-state current (lon) drivability. In this work, we suggest a gate-all-around (GAA) TFET based on compound semiconductors to improve device performances. The proposed device materials consist of InAs (source), InGaAs (channel), and InP (drain). According to the composition (x) of Ga in In1-xGa(x)As layer of the channel region, simulated devices have been investigated in terms of both direct-current (DC) and RF parameters including tunneling rate, transconductance (g(m)), gate capacitance (Cg), intrinsic delay time (tau), cut-off frequency (fT) and maximum oscillation frequency (f(max)). In this study, the obtained maximum values of tau, fT, and f(max) for GAA InAs/In0.9Ga0.1As/InP heterojunction TFET were 21.2 fs, 7 THz, and 18 THz, respectively.</P>

잘못된 Stent 삽입 치료 후 슬와 동맥 포착 증후군에서 발생한 슬와 동맥의 완전 폐쇄 1예

이인선 ( In Sun Lee ),최동훈 ( Dong Hoon Choi ),김은혜 ( Eun Hye Kim ),신상훈 ( Sang Hun Shin ),이도연 ( Do Yun Lee ),김승환 ( Seong Hwan Kim ),이택연 ( Taek Yeon Lee ) 대한내과학회 2012 대한내과학회지 Vol.83 No.6

Entrapment of the popliteal artery is a rare cause of ischemia of the lower extremities in young males. The development of local occlusive or aneurysmal changes of the popliteal artery is caused by abnormal anatomical relationships between vascular and musculotendinous structures in the popliteal fossa. A 55-year-old male patient visited Yonsei University College of Medicine with the chief complaint of claudication in his right calf. He had undergone stent insertion in the right popliteal artery for peripheral artery occlusive disease 2 years earlier. Lower extremity CT angiography showed stent fracture and in-stent thrombosis. He underwent femoral-to-popliteal artery bypass surgery. Postoperative lower extremity CT angiography showed that the vein graft was compressed between the medial head of the gastrocnemius and the semimembranosus muscle. However, the blood flow was normal and his pain was relieved. (Korean J Med 2012;83:786-790)

고온초전도체 in-situ ramp-edge 형태의 조셉슨 접합 제작 및 특성

허윤성,김진태,황윤석,이순걸,박광서,김인선,박용기,박종철,Hur, Yun-Sung,Kim, Jin-Tae,Hwang, Yun-Seok,Lee, Sun-Gul,Park, Gwang-Seo,Kim, In-Seon,Park, Yong-Ki,Park, Jong-Chul 한국재료학회 1998 한국재료학회지 Vol.8 No.3

본 연구에서는 금속 칼날 마스크와 펄스형 레이저 증착장치를 이용하여 $YBa_2Cu_3O_{7-\delta}$/$SrTiO_{3}$/$YBa_2Cu_3O_{7-\delta}$ 다층박막 형태의 In-situ SIS ramp dege 형태의 접합을 제작하였으며, 이의 특성을 조사하였다. 접합은 RSJ 형태의 전류-전압 특성ㅇ르 나타내고 있으며, 온도 변화에 따른 접합의 normal resistance는 약 $18 \omega$으로 온도에 무관하게 일정한 값을 나타내었다. 접합형태를 이용하여 감도(transfer function, dV/$d\Phi$)가 약 $22\mu$V/$\Phi_{0}$인 dc-SQUID센서를 제작하였으며, in-situ SIS ramp edge 형태의 접합이 센서로의 응용가능성을 충분히 가지고 있음을 보여 주었다. In this study, we have fabricated in-situ multilayer $YBa_2Cu_3O_{7-\delta}$/$SrTiO_{3}$/$YBa_2Cu_3O_{7-\delta}$ ramp edge type junctions by using a metal mask and pulsed laser deposition method and studied the junction properties. The junctions showed RSJ-like I-V characteristics. The normal state junction resistance R, of $18 \omega$ was nearly constant with temperature. The dc-SQUID sensors fabricated with the junctions show a sensitivity that transfer function dV/$d\Phi$)~$22\mu$V/$\Phi_{0}$, indicating that the in-situ ramp edge type junction is potentially useful for sensor application.

낙엽의 수분 변화량 현장 모니터링 시스템 개발

윤희섭 ( Heesup Yun ),이인성 ( In Sung Lee ),이훈택 ( Hun Taek Lee ),김현석 ( Hyun Seok Kim ),김학진 ( Hak Jin Kim ) 한국농업기계학회 2015 한국농업기계학회 학술발표논문집 Vol.20 No.2

선천성 폐 낭성 유선종 기형의 자궁 내 치료 바구니 모양의 도관을 이용한 흉 - 양막강 문합술 2 예

정주연(Joo Yun Chung),원혜성(Hye Sung Won),김소라(So Ra Kim),서미덕(Mi Deok Seo),황보천(Cheon Hwang Bo),김홍권(Hong Kwon Kim),이필량(Pil Ryang Lee),이인식(In Sik Lee),김암(Ahm Kim) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.10

We report a fetal therapy of two cases of type I congenital cystic adenomatoid malformation(CCAM) of the lung. The two fetuses were treated by thoracoamniotic shunting, using a basket-shaped catheter at 25 weeks' and 31 weeks' gestation, respectively. Cystic lesions of the both fetal lung were successfully decompressed after the shunt operation. Healthy babies were delivered at 41 weeks' and 38 weeks' gestation with normal Apgar score. Surgical resections of the affected lobe of the lung in the both babies were performed without complication at 1st and 7th day of birth, respectively. Shunt operation in-utero is considered as a safe and effective therapy for type I CCAM of the fetal lung.