비기능성 뇌하수체 선종의 경접형동 뇌하수체 종양 절제술 후 뇌하수체 호르몬 변화

이민석,한승진,김은경,황주안,정윤석,김세혁,조경기,임내정,김호성 대한내분비학회 2009 Endocrinology and metabolism Vol.24 No.3

Background: The present study investigated the rates and the potential predictors of either new pituitary loss or recovery of hormonal function after transsphenoidal removal of a non-functioning pituitary adenoma. Methods: Patients who underwent transsphenoidal removal of a non-functioning pituitary adenoma from January 2003 to December 2007 at Ajou University Medical Center were included in this retrospective analysis. Patients were excluded if they had a history of previous pituitary tumor surgery, or did not have preoperative pituitary hormonal data. Results: Of 42 patients included in the analysis, 36 patients had hypopituitarism, 21 patients had “stalk compression” hyperprolactinemia, and 2 patients had normal pituitary function. At long term follow-up (longer than 6 months), 13 patients showed postoperative pituitary hormonal recovery in at least 1 hormonal axis, while 6 patients had developed postoperative hormonal loss in at least 1 hormonal axis. On analysis, neither preoperative serum prolactin level nor tumor size was related to postoperative pituitary hormonal changes. Conclusion: More than 1/3 of patients who underwent transsphenoidal surgery showed postoperative pituitary hormonal recovery. Background: The present study investigated the rates and the potential predictors of either new pituitary loss or recovery of hormonal function after transsphenoidal removal of a non-functioning pituitary adenoma. Methods: Patients who underwent transsphenoidal removal of a non-functioning pituitary adenoma from January 2003 to December 2007 at Ajou University Medical Center were included in this retrospective analysis. Patients were excluded if they had a history of previous pituitary tumor surgery, or did not have preoperative pituitary hormonal data. Results: Of 42 patients included in the analysis, 36 patients had hypopituitarism, 21 patients had “stalk compression” hyperprolactinemia, and 2 patients had normal pituitary function. At long term follow-up (longer than 6 months), 13 patients showed postoperative pituitary hormonal recovery in at least 1 hormonal axis, while 6 patients had developed postoperative hormonal loss in at least 1 hormonal axis. On analysis, neither preoperative serum prolactin level nor tumor size was related to postoperative pituitary hormonal changes. Conclusion: More than 1/3 of patients who underwent transsphenoidal surgery showed postoperative pituitary hormonal recovery.

Correlation of Clinical and Immunohistochemical Diagnosis in Patients with Pituitary Adenomas

Park, Sung-Ku,Jung, Shin,Jung, Tae-Young,Kim, In-Young,Kim, Soo-Han,Kang, Sam-Suk The Korean Neurosurgical Society 2007 Journal of Korean neurosurgical society Vol.41 No.6

Objective: Pituitary adenomas are common neurological lesions believed to account for 10% to 15% of all primary brain tumors. There can be diagnostic confusion due to discordance of the preoperative endocrine and the postoperative immunohistochemical diagnosis. In this study, the rate of discordance between preoperative and postoperative findings and their clinical implications were investigated. Methods: From March 2005 to March 2006, 26 patients who underwent surgery for a pituitary adenoma were enrolled in this study. The preoperative pituitary hormone level and postoperative immunohistochemical results were compared and analyzed. Results: The median age of the patients was 38 years [range 15-66 years]. The male to female ratio was 8 to 18. The endocrine evaluation showed 16 hormonally-active and 10 hormonally-inactive adenomas. The immunohistochemical findings showed : 13 prolactin-positive, 1 GH-positive, 1 FSH-positive, 8 pleurihormone-positive and 3 stain-negative adenomas. The percentage of discordance observed between the preoperative endocrine and postoperative immunohistochemical diagnosis was 54%. Nine of 10 endocrine non-functioning adenomas showed : 3 PRL positive, 1 GH positive, 2 PRL+GH positive, 1 TSH+FSH positive, 1 FSH+ACTH+PRL positive and 1 FSH+LH+PRL positive adenomas by immunohistochemistry. Three endocrine PRL+GH secreting adenomas showed 2 PRL positive and 1 FSH+GH positive by immunohistochemistry. One endocrine PRL secreting and 1 GH secreting adenoma showed 1 PRL+ TSH positive and 1 GH+PRL positive by immunohistochemistry, respectively. The diagnosis of the other 12 pituitary adenomas showed concordance. Conclusion : The results of this study showed 54% discordance rate between the preoperative endocrine and postoperative immunohistochemical diagnosis for pituitary adenomas.

Isolation of Mesenchymal Stem-like Cells from a Pituitary Adenoma Specimen

Jin-Kyoung Shim,Seok-Gu Kang,Ji-Hyun Lee,Jong Hee Chang,Yong-Kil Hong 대한의생명과학회 2013 Biomedical Science Letters Vol.19 No.4

Some of the pituitary adenomas are invasive and spread into neighboring tissues. In previous studies, the invasion of pituitary adenomas is thought to be associated with epithelial-mesenchymal transition (EMT). In addition to that, we thought that mesenchymal stem cells (MSCs) exist in relevant microenvironment in pituitary adenoma. However, it has been little known about the existence of MSCs from pituitary adenoma. So we investigated whether mesenchymal stem-like cells (MSLCs) can be isolated from the pituitary adenoma specimen. We isolated and cultured candidate MSLCs from the fresh pituitary adenoma specimen with the same protocols used in culturing bone marrow derived MSCs (BM-MSCs). The cultured candidate MSLCs were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Candidate MSLCs were exposed to mesenchymal differentiation conditions to determine the mesenchymal differentiation potential of these cells. To evaluate the tumorigenesis of candidate MSLCs from pituitary adenoma, we implanted these cells into the brain of athymic nude mice. We isolated cells resembling BM-MSCs named pituitary adenoma stroma mesenchymal stem-like cells (PAS-MSLCs). PAS-MSLCs were spindle shaped and had adherent characteristics. FACS analysis identified that the PAS-MSLCs had a bit similar surface markers to BM-MSCs. Isolated cells expressed surface antigen, positive for CD105, CD75, and negative for CD45, NG2, and CD90. We found that these cells were capable of differentiation into adipocytes, osteocytes and chondrocytes. Tumor was not developed in the nude mice brains that were implanted with the PAS-MSLCs. In this study, we showed that MSLCs can be isolated from a pituitary adenoma specimen which is not tumorigenic.

라스케씨 열낭종과 동시에 발생한 뇌하수체 선종

김정훈 ( Jeong Hoon Kim ),권순찬 ( Soon Chan Kwon ),안재성 ( Jae Sung Ahn ),전상룡 ( Sang Ryong Jeon ),나영신 ( Young Shin Ra ),김창진 ( Chang Jin Kim ),이정교 ( Jung Kyo Lee ) 대한뇌종양학회 2003 대한뇌종양학회지 Vol.2 No.2

Objective:The goal of this study was to characterize the clinical, radiological, surgical, and pathological findings in patients with both pituitary adenoma and Rathke`s cleft cyst. Methods:We conducted a retrospective study of patients with concomitant pituitary adenoma and Rathke`s cleft cyst operated on from 1991 through 2001 at our institution. Three patients were identified with this diagnosis. The medical records, neuroradiologic studies, and histologies were reviewed. Results:There were 771 patients with pituitary adenoma and 46 with Rathke`s cleft cyst in the same period. The frequency of the combination was 0.39 % of pituitary adenoma and 6.5% of Rathke`s cleft cyst. One case was associated with hyperprolactinemia. Preoperative diagnosis on the basis of CT/MRI was pituitary adenoma in all three cases. Transsphenoidal approaches were done for these three patients, and postoperative courses were uneventful. Hormonal and visual symptoms were improved. Histologically, the tumor was composed of typical pituitary adenoma and component compatible with Rathke`s cleft cyst. Conclusion:When a non-enhancing cyst-like structure is demonstrated in a patient with pituitary adenoma, the possibility of a coexisting Rathke`s cleft cyst should be considered. Patients with this kind of pituitary tumor can be managed in the same fashion as patients with other types of pituitary adenoma.

Recent Progress in the Medical Therapy of Pituitary Tumors

Fabienne Langlois,Shirley McCartney,Maria Fleseriu 대한내분비학회 2017 Endocrinology and metabolism Vol.32 No.2

Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

뇌하수체 선종의 면역조직화학 검색

이용희,김태승 대한병리학회 1994 Journal of Pathology and Translational Medicine Vol.28 No.6

면역세포화학 염색법과 전자 현미경검사를 통한 뇌하수체 선종의 특징

이은직(Eun Jig Lee),이현철(Hyun Chul Lee),양우익(Woo Ik Yang),김경래(Kyung Rai Kim),김현만(Hyun Man Kim),안광진(Kwang Jin Ahn),정윤석(Yoon Sok Chung),임승길(Sung Kil Lim),김태승(Tae Seung Kim),박찬일(Chan Il Park),최인준(In Joon choi 대한내과학회 1992 대한내과학회지 Vol.43 No.2

Background: The development of immunocytochemistry and the application of electron microscopy improved the knowledge of the pathology and classification of the pitutiary adenomas. We investigated the characteristics of the pituitary adenomas examined by the immunocytochemistry and electron microscopy. Methods: 44 patients with the pituitary adenomas were investigated, using immunocytochemical techniques in paraffin-embedded tissue, and electron microscopy in fresh tissue. Results: The mean age was 38±13 years, and the ratio of male to female was 1: 2.4 and 18 were prolactinomas, 8 acromegalies, 3 acromegalies with hyperprolactinemia, 3 Cushing`s diaseases, 3 FSH secreting adenomas, 1 TSH secreting adenomas, and 6 nonfunctioning adenomas among 44 patients. The agreement between serum prolactin and prolactin immunocytochemistry was 77.3% if the serum prolaetin level to predict lactotrope adenoma was above 50ng/ml; however, the agreement was 93,2% if the serum prolatin level above 100ng/ml. The serum levels of prolactin and growth hormone in sparsely granulated lactotrope and somatotrope adenomas were 1149.6, 109.5ng/ml, respectively, which were higher than those (129.6, 35.9ng/ml) of densely granulated ones. Immunocytochemical and electron microscopic analysis revealed that thirteen were lactotrope adenomas (12 sparsely granulated, and 1 densely granulated), 9 somatotrope adenomas (6 sparsely granulated and 3 densely granulated), 6 gonadotrope, 4 corticotrope (3 symtomatic and 1 silent), 1 mixed somatotrope and lactotrope, 1 mammosomatotrope, 1 thyrotrope, and 9 null cell (6 nononcocytic, and 3 oncocytic) adenomas. Conclusion: The immunocytochemistry, permitting the visualization of intracellular hormones in the tissue of the pituitary adenoma, made exact histologic diagnosis. So, we have known whether the cause of hyperprolactinemia was lactotrope adenoma or functional hyperprolactinemia due to PIF inhibiton. And it was also possible to diagnose silent corticotrope adenoma and gonadotrope adenoma which had no apparent clinical manifestation. Electron microscopic examination of the pituitary adenoma diagnosed by immunocytchemistry showed ultrastructrural characteristics of the adenoma cells containing each hormones, Accordingly, we could subclassify the pituitary adenoma. However, the identification of the adenomas with somewhat similar ultrastrutural features such as null cell, gonadotrope, and thyrotrope adenoma, may be facilitated by immunocytochemistry. Accordingly, both immunocytochemistry and electron microscopy are necessary for the identification and characterization of the pituitary adenomas.

Endocrine Outcome of Endoscopic Endonasal Transsphenoidal Surgery in Functioning Pituitary Adenomas

Choe, Jai-Ho,Lee, Kun-Soo,Jeun, Sin-Soo,Cho, Jin-Hee,Hong, Yong-Kil The Korean Neurosurgical Society 2008 Journal of Korean neurosurgical society Vol.44 No.3

Objective : Microscopic and endoscopic transsphenoidal approach (TSA) are major surgical techniques in the treatment of pituitary adenoma. Endoscopic endonasal transsphenoidal approach (EETSA) has been increasingly used for pituitary adenomas, however, its surgical outcome particularly in functioning pituitary adenoma has been debated. Here, we investigated the endocrine outcome of the patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenoma treated by EETSA. Methods : We treated 80 patients with pituitary adenoma by EETSA since 2004, of which 12 patients were affected by functioning pituitary adenomas (9 GH, 3 ACTH, 0 PRL; 9 macro, 3 micro). Surgical outcome of those patients treated by EETSA was compared with that of the 11 functioning pituitary adenoma patients (8 GH, 3 ACTH; 8 macro, 3 micro) who underwent sublabial microscopic TSA between 1997 and 2003. Results : Imaging remission based on postoperative MRI was achieved in 8 (73%) and hormonal remission in 5 (45%) of 11 patients treated by sublabial microscopic TSA. Imaging remission was observed in 10 (83%, p=0.640) and hormonal remission in 10 (83%, p=0.081) of 12 patients by EETSA. CSF leakage was noticed in 2 (17%) of EETSA group and in 2 (18%) of sublabial microscopic TSA group. Panhypopituitarism was observed in 1 (9%) of EETSA group and in 3 (27%) of sublabial microscopic TSA group. Conclusion : EETSA appears to be an effective and safe method for the treatment of functioning pituitary adenomas.

Analysis of Circulating Endostatin and Vascular Endothelial Growth Factor in Patients with Pituitary Adenoma Treated by Stereotactic Radiosurgery: A Preliminary Study

( Kyung-min Lee ),( Seong-hyun Park ),( Ki-su Park ),( Jeong-hyun Hwang ),( Sung-kyoo Hwang ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2015 Brain Tumor Research and Treatment Vol.3 No.2

Background The purpose of this study was to investigate plasma levels of endostatin and vascular endothelial growth factor (VEGF) in normal subjects and in patients with pituitary adenoma and to evaluate change in these levels following stereotactic radiosurgery (SRS) for pituitary adenoma. Methods Peripheral venous blood was collected from five patients with pituitary adenoma before SRS using Gamma Knife and at the 1 week and 1 month follow-up visits. Plasma endostatin and VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. Results Mean baseline plasma endostatin level (105.3 ng/mL, range, 97.0-120.2 ng/mL) in patients with pituitary adenoma was higher than that of the healthy controls (86.6 ng/mL, range, 71.3- 98.2 ng/mL) (p=0.001). Mean plasma VEGF level was 89.5 pg/mL (range, 24.1-171.8 pg/mL) in patients with pituitary adenoma at baseline and 29.3 pg/mL (range, 9.2-64.3 pg/mL) in the control group (p=0.050). Plasma endostatin level changed to 106.6 ng/mL 1 week after SRS and decreased to 95.9 ng/mL after 1 month. Plasma VEGF level following SRS decreased to 74.1 pg/mL after 1 week and 79.0 pg/mL after 1 month. There was a trend toward decreased plasma endostatin and VEGF concentrations 1 month after SRS compared to baseline levels (p=0.195, p=0.812, respectively). Conclusion Plasma endostatin and VEGF levels in patients with pituitary adenoma were signifi- cantly elevated over controls at baseline, which decreased from baseline to 1 month after SRS for pituitary adenomas.

소아 및 청소년기의 뇌하수체선종

김은영,최중언,정상섭,이규창,김덕희 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.8

Between 1989 and 1993. 13 patients with pituitary adenoma underwent operation/radiosurgery at Yonsei University Hospital before their 18th birthday. This comprises an incidence of 5.3%(13/247)of all pituitary adenoma patients who were treated at our institution during the study period. There were 7 boys and 6 girls ranging in age from 10.6 to 17.9 years(average, 14.9 years). The mean follow-up period was 22.4 months(7-55 months). Immunohistochemical study revealed 4 prolactin(PRL)-secreting 3 growth hormone(GH)-secreting(PRL was also positive in one), 1 adrenocortical hormon(ACTH)-secreting, 1 thyroid stimulating hormone(TSH)-secreting, and 4 non-functioning adenomas. Nine of 13 patients(77%) presented with symptomatic endocrinopathy due to hormonal hypersecretion and/or delay in linear growth or onset of puberty. Microadenomas comprised one of nine functioning adenomas, and one of 4 nonfunctioning adenomas, or 15% overall. In 10 patients(77% ). at least one pituitary hormonal axis was abnormal. Transsphenoidal and transcranial resections were employed in 8 and 4 patients, respectively. One patient with nonfunctioning microadenoma underwent gamma knife radiosurgery. Endoclinologically successful treatment was possible in 4 of 9 functioning adenomas(44%). Grosstotal resections confirmed by follow-up study were achieved in 2 of 3 nonfunctioning adenomas. One nonfunctioning microadenoma treated by radiosurgery showed no progession on follow-up study 20 months after radiosurgery. Seven patients(54%) were treated successfully with either operation or radiosurgery. Adjuvant therapy was applied to 5 patients. Overall tumor control was achieved in 91%. Long-term partial or full hormone replacement was necessary in 69%. It is concluded that early diagnosis, vigorous approach to complete cure, and more strict endocrinological management for sexual maturation and growth are mandatory in the management of pediatric pituitary adenomas.