A Preliminary Study On The Mechanism Of Hemorrhagic Pituitary Adenoma Apoplexy

PART Ⅰ Analysis of risk factors related to hemorrhagic pituitary adenoma apoplexy Objective: To investigate and analyze the risk factors of hemorrhagic pituitary adenoma apoplexy and reveal the possible mechanism of hemorrhagic pituitary adenoma apoplexy caused by risk factors,and then to provide strategy and direction for clinical prevention,diagnosis and treatment of hemorrhagic pituitary adenoma apoplexy.Methods: The clinical date of 875 patients with non-functioning pituitary adenomas from January 2013 to January 2019 in the department of Neurosurgery,Affiliated Hospital of Qingdao University,was analyzed retrospectively.Among the patients,there are 88 cases had pituitary adenoma apoplexy,and 787 cases without pituitary adenoma apoplexy.According to the clinical manifestations,imaging examination,endocrine examination,intraoperative findings and postoperative pathology,the patients were divided into pituitary adenoma apoplexy group and non-apoplexy group.The clinical date was compared between pituitary adenoma apoplexy group and non-apoplexy group.Univariate and multivariate logistic regression analysis was performed to analysis the risk factors of pituitary adenoma apoplexy.Results: The proportion of taking antithrombotic drugs,recurrent or residual tumor,interventional operation and bromocriptine therapy in pituitary adenoma apoplexy group were higher than non-apoplexy group;the proportion of microadenoma in pituitary adenoma apoplexy group was lower than non-apoplexy group,and difference between the two groups has statistical significance(P < 0.05).The preoperative average dose of bromocriptine therapy in apoplexy group were higher than non-apoplexy group,and difference between the two groups has statistical significance(P<0.05).Multivariate logistic regression analysis indicated that macroadenoma,taking antithrombotic drugs,recurrent or residual tumor and bromocriptine therapy were independent risk factors of hemorrhagic pituitary adenoma apoplexy.Conclusion: 1.The incidence of hemorrhagic pituitary adenoma apoplexy has no correlation with age,sex,radiotherapy,hypertension,diabetes,smoking,drinking.2.Macroadenoma,taking antithrombotic drugs,recurrent or residual tumor and bromocriptine therapy were independent risk factors of hemorrhagic pituitary adenoma apoplexy.PART Ⅱ A study on the correlation between CD34,TNF-α,VEGF,MMP-9 and hemorrhagic apoplexy in non-functioning pituitary adenomasObjective: To explain the possible pathological mechanism of hemorrhagic pituitary adenoma apoplexy,then to explore the possible role of CD34,VEGF,TNF-α and MMP-9 in hemorrhagic pituitary adenoma apoplexy,and to explore the difference of the expression of these four proteins between hemorrhagic pituitary adenoma apoplexy and non-apoplexy pituitary adenomas.It is expected to provide a better theoretical basis for the prevention of hemorrhagic pituitary adenoma apoplexy and the screening of therapeutic targets in the future.Methods: The pathological tissue specimen of 40 patients with non-functioning pituitary adenoma treated by surgery from December 2016 to December 2019 in the department of Neurosurgery,Affiliated Hospital of Qingdao University,were collected.According to the preoperative clinical manifestations,imaging examination,intraoperative findings and postoperative pathological results,40 patients were divided into hemorrhagic pituitary adenoma apoplexy group(20cases)and non-apoplexy group(20cases).Immunohistochemical methods was used to detect the expression of CD34,VEGF,TNF-α and MMP-9 in the specimens.The positive expression standard of CD34 was determined by Weidner method,and the average value of microvessel density(MVD)in pituitary adenoma apoplexy group and non-apoplexy group was calculated respectively;the positive expression standard of TNF-α,VEGF and MMP-9 were determined by IRS semiquantitative method,and the positive expression rates of apoplexy group and nonapoplexy group were calculated respectively.Using statistical methods to compare the differences between the two groups.Spearman rank correlation was used to analyze the correlation among MVD,VEGF,TNF-α and MMP-9 in hemorrhagic pituitary adenoma apoplexy group.Results: 1.Comparison between apoplexy group and non-apoplexy group: the average value of MVD in apoplexy group and non-apoplexy group were respectively 29.30±4.34 and 22.10±3.68,and difference between the two groups has statistical significance(t=5.655,P﹤0.01);the positive expression rates of TNF-α in apoplexy group and non-apoplexy group were respectively 45% and 20%,and difference between the two groups has no statistical significance(x~2=1.026,P=0.311﹥0.05);the positive expression rates of VEGF in apoplexy group and non-apoplexy group were respectively 80% and 45%, and difference between the two groups has statistical significance(x~2=5.227,P=0.022﹤0.05);the positive expression rates of MMP-9 in apoplexy group and non-apoplexy group were respectively 65% and 30%,and difference between the two groups has statistical significance(x~2=4.912,P=0.027﹤0.05).2.Correlation among MVD,VEGF,TNF-α and MMP-9 in hemorrhagic pituitary adenoma apoplexy group: the expression of VEGF and MVD has significant positive correlation(r=0.566,P=0.009<0.01);the expression of MMP-9 and MVD has significant positive correlation(r=0.593,P=0.006<0.01);the expression of VEGF and MMP-9 has significant positive correlation(r=0.681,P=0.001<0.01).Conclusion: 1.High expression of VEGF,MMP-9 and high MVD are closely related to hemorrhagic apoplexy in non-functional pituitary adenomas.2.High expression of VEGF and MMP-9 promotes the neovascularization and increases the MVD in pituitary adenomas.And then it increases the risk of hemorrhagic pituitary adenoma apoplexy.Moreover,VEGF and MMP-9 play a synergistic effect in the process of hemorrhagic pituitary adenoma apoplexy.3.Inhibiting the expression of CD34,VEGF and MMP-9 may be a potential treatment for the prevention of hemorrhagic pituitary adenoma apoplexy in the future.