Pituitary Apoplexy In Nonfunctioning Adenomas: The Characteristics In Clinical Diagnosis And Treatment And The Impact On Tumor Invasion

Pituitary adenoma what is a neuroendocrine tumor account for 10% in brain tumors.Macroadenoma is characterized as low visit rate,low resection rate,and bad prognosis.Accompanied by the rapid progress of endocrinology and neuroimaging skills,more and more studies reported that pituitary apoplexy happened commonly in pituitary adenomas,especially in macroadenomas.The early studies of pituitary apoplexy were almost concentrated on those acute/clinical cases.While there have been recently more attentions to pituitary subclinical apoplexy.It could result from the more subacute/subclinical cases of pituitary apoplexy than the classical cases by neuroimaging.It was noteworthy that most studies of pituitary apoplexy were limited to retrospective ways,because of the complicated pathophysiology of pituitary apoplexy,which is a lack of reliable prospective study.There are lots of unknown domains need to be explored in order to improve patients' outcomes.This paper aims to illuminate the effect of pituitary apoplexy on the diagnosis and treatments of pituitary adenoma from the studies of symptomatic characteristics,neuroimaging,endocrinology,tumor resection rate and the expressions of correlative genes/proteins.There are three sections of the paper.The first section will retrospectively analyze total 194 cases of pituitary macroadenomas.The second section will try to discuss the effect of pituitary apoplexy on pituitary-gonadal axis in male patients by retrospective and cross-sectional ways.According to the outcomes of tumor resection rate and extent of invasion in section one,The third section will test the expression of genes/proteins of Ki-67,VEGF,CD34 in different types of pituitary apoplexy in order to explore the correlations among pituitary apoplexy,tumor resection rate and extent of invasion.Part ? Apoplexy in nonfunctioning pituitary macroadenomas: a retrospective research-human-clinical studyObjective: Our aim is to explore the influence of pituitary apoplexy in clinical symptoms,neuroimaging,outcomes of surgery and prognosis.Methods: This is a retrospective study of 194 consecutive patients with nonfunctioning pituitary macroadenomas,who were treated surgically by the endoscopic endonasal transsphenoidal approach in the Department of Neurosurgery at Changzheng Hospital,Shanghai from Jun 1,2012,to Dec 31,2015.All cases were classified into the non-apoplexy,hemorrhagic apoplexy or ischemic apoplexy group.Results: The patients of the hemorrhagic apoplexy group are more timely than the ischemic apoplexy group ones for finding treatments(P<0.001).The macroadenomas of ischemic apoplexy group seems to be the widest extent of invasion in three groups(Hardy's grade: P=0.013;Knosp grade: P=0.008).Hemorrhagic apoplexy appeared generally as a single shape,while more ischemic apoplexy presented with multiple shapes(P=0.005).There was ischemic apoplexy occurred in the suprasellar region and hemorrhagic apoplexy occurred in the intrasellar region(P<0.001).We also found that the improvement of a headache in the ischemic apoplexy group was better than the hemorrhagic apoplexy group(P=0.05).Finally,the tumor resection rate of the ischemic apoplexy group is better than the other groups(P=0.031).Conclusion: Pituitary adenomas in the HA group could be operated in a timely manner in order to gain a good prognosis.Ischemic apoplexy in adenoma,accompanied by a late treatment,invaded the wide regions.It is,therefore,essential to pay close attention to distinguish apoplectic types when making treatment protocols and assessing prognosis.Part ? Apoplexy in nonfunctioning pituitary macroadenomas with hypogonadismObjective: The objective of this study was to analyze the fluctuations of pituitarygonadal axis in the male by the apoplectic events.Methods: The study of the retrospective section was carried out to analyze the correlations between the gonadal hormones in male and tumor size in the apoplectic event,and then followed up all cases within 1 year after surgery.The cross-sectional study was achieved to analyze serum FSH,LH,Free testosterone levels by Elisa assay,and then tried to verify the correlation between gonadal hormones in male and tumor size.Results: Our study revealed that there were linear correlations in males between pre-operative gonadal hormones and preoperative tumor volumes in the non-apoplexy group(FSH: P<0.001;LH: P<0.001)and in hemorrhagic apoplexy group(Before: FSH: P=0.006;LH: P=0.001);(After: FSH: P=0.009;LH: P=0.001).Similar linear correlations were gained by Elisa assay(NA group: FSH: P=0.036;LH: P=0.035;HA group: FSH: P=0.033;LH: P=0.036).Finally,the above phenomenon did not appear in ischemic apoplexy group.Conclusion: Following the tumor size proliferating,the gonadotropic functions in the male of HA and NA group fall off.But the atypical symptom of gonadal deficiency masked partly the fact of gonadotropic decline.Pituitary-gonadal function seems to be a sensitive predictor for the normal gland.Distinguishing the apoplectic types may be useful for assessing prognosis and establishing treatment protocols.Part ? The effects of pituitary apoplexy on extent of invasion and tumor resection rateObjective: In this section,we tested the expressions of gene KI67,VEGF,CD34 and their proteins in pituitary adenoma tissues of three different apoplectic types.Combining the clinical data,we statistically analyzed the effect of the apoplectic events on tumor's invasion,resection rate,and occurrence rate.Methods: The expression of KI67,VEGF,and CD34 in total 36 pituitary adenoma tissues was investigated using quantitative real-time PCR and immunohistochemistry(IHC)assay.According to the images of sellar MRI before and after surgery,the tumor sizes of all cases were calculated in order to assess tumor resection rate.Finally,the effects of pituitary apoplexy on extent of invasion,tumor resection rate and occurrence rate were statistically explored.Results: The results showed that the expression of KI67 in IA group was higher than in HA group(P<0.05)and the expression of CD34 in NA group was higher than in HA group(P=0.018),whereas no difference appeared in the expression of VEGF.Moreover,the results of IHC assay found that positive staining of KI67 appeared in the tissues of pituitary apoplexy rather than the tissues of non-apoplectic apoplexy and that positive staining of VEGF appeared in the cells of non-apoplectic group rather than the apoplectic ones.Conclusion: The ability of tumor invasion of ischemic apoplexy is better than hemorrhagic apoplexy,but it seems not to be associated with angiogenesis in pituitary adenoma.It is useful for softening tumor and improving the resection rate to cut the blood supply of pituitary adenoma.But better resection rate seems not to suppress tumor recurrence rate.It still needs lots of prospective clinical trials to study the effect of pituitary apoplexy on prognosis.