Serum Hormone Levels,Cognitive Function,and Magnetic Resonance Imaging In Patients With Pituitary Adenomas

Pituitary adenoma(PA)originates from the pituitary gland of the brain,and the incidence accounts for 10～25%of all central nervous system(CNS)tumors.The prevalence in the general population is around 17%,being the second frequently reported histology in CNS tumors.Most pituitary adenomas are benign,but about 35%of adenomas are invasive.The clinical manifestations of patients with pituitary adenomas may vary according to the different disease subtype.Patients with functional pituitary tumors may exhibit corresponding symptoms due to excessive hormone secretion,such as Cushing’s syndrome,acromegaly,amenorrhea,decreased reproductive capacity,and decreased bone mineral density.As results of the mass occupying effect of the pituitary adenoma,the patient suffering a non-functional pituitary tumor often has clinical symptoms such as headache,vision loss,visual field damage,and secondary pituitary dysfunction.In recent years,with the continuous advancement of treatment techniques for pituitary adenomas,doctors have the ability to control the endogenous hormone disorders in patients with Pas and reduce the compression of the surrounding tissues and improve the pituitary insufficiency.As a result,a considerable number of patients could reach endocrinological cure and radiological cure,and the mortality of PAs has decreased significantly.However,emerging studies across the world have reported that patients with pituitary adenomas still show poor quality of life,cognitive dysfunction,and emotional disorders,such as memory loss,decreased attention,reduced selfcontrol ability,anxiety,and depression;therefore,we can not simply think that these patients are "completely healthy." To shed more lights on this pending question,we carried out the prospective cross-sectional cohort study to explore the underlying neural mechanisms separately from the perspective of serum hormone levels,cognitive function,and modal-modal magnetic resonance imaging(MRI)techniques in patients with PAs.The main research work of this thesis includes the following three parts:First,we prospectively recruited 32 female patients with a clinical diagnosis of prolactinomas and 26 healthy controls matched with age,gender,education,and dominant handedness.The serum hormone levels of patients with pituitary tumors were collected and neuropsychological assessments were performed for all participants.The evaluation items included the Wisconsin Card Switch Test(WCST)and the modified Chinese version of the Wechsler Memory Scale-Revised(WMS-R,Chinese version).Subsequently,the partial correlation analysis revealed that female patients with prolactinoma had significant hormone disorders and dysfunctional cognitions.Among them,the high level of prolactin in patients had a significant negative-feedback inhibition on the secretion of other endocrine hormones.For example,the inhibition of estradiol,testosterone,follicle stimulating hormone,and luteinizing hormone secretion.Patients with cognitive dysfunction mainly involved executive function and verbal memory;and the higher prolactin concentration in serum,the more severe decline in cognitive functions.Second,all participants were from the same dataset with that in part one.The three-dimensional(3-D)high-resolution magnetic resonance image(MRI)data were collected from all participants.The voxel-based morphometry(VBM)method was employed to analyze the 3D structural MRI data to map the gray matter structure of the brain.The VBM analysis method has shown high reproducibility and can be used to characterize the whole brain structural property.Compared to HC,female patients with prolactinomas demonstrated a decrease in gray matter volume(GMV)in the left hippocampus,left orbitofrontal cortex,right middle frontal cortex(MFC),and right inferior frontal cortex(IFC).In addition,patients performed worse than controls on tests for verbal memory and executive function,and this was significantly related to the GMV of the left hippocampus and right MFC,respectively.Moreover,in the patients,we found a negative relationship between serum prolactin levels and the GMV of the left hippocampus and right IFC,whereas a positive relationship was found between the GMV of the left hippocampus and serum levels of estradiol and luteinizing hormone.In patients with prolactinomas,specific brain structure abnormalities have been identified and are associated with cognitive impairments and dysfunctional hormones.This study enhances our understanding of brain structure changes that may occur with prolactinomas and provides novel and fundamental evidence for previous behavioral findings relevant to hyperprolactinemia.In the final part of this study,we prospectively recruited 95 patients with clinical diagnosis of PAs including 33 cases of prolactinomas,53 cases of non-functional pituitary adenomas(NFPA),and 9 cases of somatotrophic adenomas(SomTA);31 healthy controls were matched for age,gender,education,and dominant handedness.Serum hormone levels were collected from all patients and 3D structural MRI data and resting-state functional MRI(RS-fMRI)data from all participants.The region-based region of interest(ROI)data analysis was employed to characterize resting state functional connectivity(RSFC)and functional connectivity(FC)within the default mode network(DMN).It was found that there was a significant abnormality in the RSFC across the whole brain and the FC within the DMN in patients with prolactinomas,NFPA,and somatotrophic adenomas(SomTA),respectively.First,the patients with prolactinoma presented significant FC increase between the cerebellum and temporal fusiform cortex and posterior cingulate cortex/precuneus.RSFC between the left thalamus and the parietal cortex and occipital cortex also decreased significantly and showed sex differences.In female patients,prolactin and thyrotropin showed positive relationship with increased functional connectivity,reflecting that the two hormones involved in the brain hyperactivity,which may be related to the anxiety in patients.Meanwhile,the FC between the posterior cingulate cortex and the precuneus within the DMN in patients with prolactinoma significant reduction may be another potential neural mechanism for emotional abnormalities in patients with PAs.Secondly,we also found that the RSFC across the whole brain in patients with NFPA showed different RSFC patterns under different statistical thresholds.Regarding the decline of FC within the DMN,findings can be interpreted to character the transient pattern of brain FC during a different period of disease progression,from compensatory FC to another status of decompensated FC.Finally,SomTA patients mainly showed a widespread increase in RSFC,which often occurred in the early stage of the tumor volume gradually increasing,reflecting the neuroplasticity and RSFC compensation.The FC within the DMN performed both enhanced connection and weakened FC,demonstrating that the FC indicators within the DMN can better describe the alternation process of brain dysfunction in this type of patient.