| Background and ObjectiveHypopituitarism refers to one or more of the anterior pituitary hormone and/or posterior lobe hormone gland hormone secretes inadequacy or can not meet the normal needs of the body; pituitary function decline refers to the narrow sense of anterior pituitary dysfunction. The prevalence of hypopituitarism is 4.55/10000, and increased with the increase of age. The pituitary gland is the most important human central endocrine gland, located at the center of hypothalamus pituitary target gland axis. Deficiency can cause a variety of effects on human pituitary hormone secretion, such as sexual dysfunction, stress ability, growth retardation, body composition changes, mental apathy; among them the most serious effects on the body is to increase the risk of human respiratory and cardiovascular disease, high mortality rates among the population provided, reduce long-term natural survival rate. The age, women and craniopharyngioma history is the main factor that hypopituitarism mortality rate increased.Pituitary dysfunction according to different causes were:primary pituitary insufficiency and secondary hypopituitarism, with secondary hypopituitarism is common. Primary pituitary pituitary dysfunction refers to by the pituitary itself caused by the disease, including idiopathic hypophysitis, congenital hereditary hypopituitarism etc.. While the secondary hypopituitarism pituitary gland disease caused by means other than, including sellar region tumor, brain trauma, infection and inflammation, operation injury and emission injury; wherein the sellar region tumor accounted for the first,61%. Non functional pituitary adenoma and craniopharyngioma is a cause of pituitary function in sellar region tumor caused by loss of the most common. Reports in the literature, cranial pharyngeal hypophysis function caused by the decline rate was higher than other non functional pituitary adenoma and other diseases.Sellar region tumor is mainly through the compression of the pituitary or pituitary stalk, thus undermining the normal blood supply of the pituitary gland, or affect the secretion of hypothalamic endocrine hormone caused by pituitary hypofunction. Generally, the more aggressive the tumor, the higher the incidence of pituitary hypofnction. Research has also shown that hypopituitarism incidence and intrasellar pressure is positive correlation, but the pressure of tumor size and intrasellar no correlation.Comparison of craniopharyngioma and nonfunctional pituitary adenoma, in addition to the size of the tumor may exist differences. Differences between the two types of tumors are shown in two aspects. One is the site of origin of craniopharyngeal duct tumor, craniopharyngioma can occur in any part of the oropharynx to floor of the third ventricle in Rathke’s capsule. Some scholars according to origin, the craniopharyngioma is divided into suprasellar origin craniopharyngioma (Q type); saddle external ventricular cobweb end subarachnoid type tumor (S type) and suprasellar craniopharyngioma funnel nodular type (T type).The oppression of tumor different origin sites on the hypothalamus, pituitary, pituitary portal system impact may be different. The pituitary adenomas were originated from the anterior pituitary in the saddle. Two is the craniopharyngioma memory in tissue inflammation obvious. Craniopharyngioma cyst fluid overflow can cause aseptic meningitis, prompting the cystic fluid may contain inflammatory cytokines, inflammation reaction mediated by the tumor and surrounding tissue. Craniopharyngioma adamantinomatous type, especially with the surrounding normal brain tissues often have inflammation adhesion, make surgery difficult to total resection of the tumor, cause postoperative tumor recurrence, was significantly related to the degree of inflammation and prognosis in patients with. Reports in the literature of interleukin 6 in cranial pharyngeal abnormal expression of craniopharyngioma, may be the cause of craniopharyngeal important inflammatory duct tumor inflammation medium, affects the prognosis of patients.Inflammation is a defensive reaction of organism and tissue damage factor to the outside world. The basic pathological changes of inflammation often summarized as local tissue deterioration, exudation and proliferation. During inflammation, damage factor can have direct or indirect impact on tissue and cell damage and inflammation, congestion and exudation, can be diluted, surrounded by killing and damage factor. In addition, inflammation by stimulating the parenchymal and mesenchymal cell regeneration of damaged tissue to repair and healing. Therefore, inflammation is a unified process of damage and anti damage. In general, inflammation is the local reaction of natural give priority to defense, is favorable to the body of the pathological process. But in some cases, inflammation is harmful. For example, inflammation of special parts or organs can cause serious consequences, such as vocal inflammatory obstruction throat cause asphyxia, severe myocarditis can affect heart function. The close relationship between tumor associated inflammation and tumorigenesis, development very closely. On the one. On the one hand can play the anti tumor effect; on the other hand, inflammatory cells and inflammatory factors can promote tumor formation, proliferation, invasion and metastasis. At the same time can lead to inflammation and/or autoimmune reaction tissue around the tumor.The kinds and quantity of inflammatory factors involved in inflammatory reaction of variety. Is generally believed that played a major role in the TNF-alpha, IL-1 beta, IL-6, IL-8, TGF-P. TNF-alpha is inflammatory mediators in the earliest, most important inflammatory reaction process, can activate neutrophils and lymphocytes, the vascular endothelial cell permeability increased regulation, synthesis of other tissue metabolic activity and prompt other cytokines and release. IL-1 is a secreted by monocytes and tissue macrophages in the blood of the proinflammatory cytokine, plays an important role in acute and chronic inflammation. IL-6 can induce the differentiation of B cells and antibody production, and induction of T cell activation and proliferation, differentiation, immune response in the body of the inflammatory response, is precipitating agent. IL-8 can stimulate the neutrophilic granulocyte, T lymphocyte and eosinophil chemotaxis, promotes neutrophil degranulation and release of elastase, endothelial cell injury, microcirculation of blood stasis, tissue necrosis, resulting in organ function injury. Now think the inflammatory response to TNF, IL-1, IL-6 induced in the very great degree is induced by IL-8 as the representative to the chemokine mediated. IFN-alpha can be enhanced via T, B lymphocyte, NK cell and macrophage function, promote the body to cell killing and clearance, thus plays the immune surveillance and immune regulation effects. IFN-gamma has the ability to regulate immunity, can promote the phagocytosis of macrophage immune complexes and antibody coated pathogens, by stimulating the body’s innate and adaptive immunity and strengthen immune surveillance function for its effect. IL-10 is an immunomodulatory cytokine production and cell proliferation, cytokine which can inhibit CD4+CD8+T cell, B cell isotype can regulate the conversion, also can change the function of antigen presenting cells. IL-12 was mainly secreted by antigen presenting cells, antigen stimulated macrophages, dendritic cells and B cells are a major source of IL-12. IL-12 biological activity is mainly to promote T cell proliferation and induce T cell killing activity, can develop mediated Th type immune responses in the immune process. MCP-1 is a CC chemokine include chemotaxis of mononuclear macrophages and T lymphocytes. Through the combination of MCP-1 and monocyte/macrophage surface specific CCR2 receptor to activate and chemotaxis of monocytes/macrophages. MIP-1 plays a chemotactic inflammatory cell and degranulation, promote phagocytosis and regulating inflammatory cytokines synthesis.In this study, by analyzing the clinical data, to study the craniopharyngioma and non functional pituitary adenoma pituitary dysfunction rate characteristics; comparison of Q pituitary function type craniopharyngioma and non functional pituitary line loss incidence; through liquid phase suspension chip experiment method of craniopharyngioma and non functional pituitary adenoma tumor tissue, blood samples and craniopharyngioma cell culture samples for detection of common tumor related inflammation factors, to explore the effect of inflammatory factors on pituitary function decline.Materials and methods1 Clinical data1.1. ObjectIn this study, a retrospective analysis of 2005 June to 2014 South Hospital Department of neurosurgery in June 264 cases of intracranial in-patient treatment of craniopharyngioma and 231 cases of imaging endocrine examination results of nonfunctional pituitary adenoma patients and sellar region data, including prolactin, testosterone, estradiol, luteinizing hormone, follicle stimulating hormone, cortisol, thyroid stimulating the function of adrenal cortex hormone, (thyrotropin, free T3 and free T4, T3 and T4), growth hormone and insulin like growth factor-1. Inclusion criteria:1 patients in the hospital before he treatment (both for tumor treatment, hormone replacement therapy, surgery and stereotactic radiotherapy etc.) patients; 2 imaging data complete, clear sellar; and for surgery and postoperative pathology can be clearly diagnosed cases.1.2. Research methodsIn accordance with the pituitary function axis diagnostic criteria are lacking, for endocrine assessment in 495 patients. Comparison of different tumor size, different surgical credit type craniopharyngioma pituitary dysfunction rate characteristics. Comparison of different tumor size non functional pituitary adenoma pituitary dysfunction rate characteristics. The non functional pituitary adenomas with suprasellar craniopharyngiomas tumor size and hypopituitarism incidence were compared.2. Experiment materials and methods2.1 SubjectsCollected 35 cases of tumor specimens and clinic data(10 cases of craniopharyngioma,25 cases of non functional pituitary adenoma); also collect the corresponding craniopharyngioma patients with peripheral blood samples and tumor samples for cell culture.2.2. Experimental treatmentUsing trypsin digestion method to enamel epithelium extracranial fresh craniopharyngiomas tissues of primary culture, passage and then the purified routine, the third generation of craniopharyngioma cell into cell suspension. Extraction of tumor tissue specimens and craniopharyngioma cell samples using cell lysates inflammatory factor. The enzyme mark instrument by determining the extract and blood protein concentration. The use of inflammatory factors of liquid chip detection under the same concentration, all IL-1 specimens and samples in alpha, IL-1 beta, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, IFN-alpha, MCP-1, factor MIP-1 levels. And the comparison of craniopharyngioma patients and non functional pituitary adenoma patients with endocrine situation.3. Statistical processingMeasurement data using analysis of variance, count data using chi square test 2. Taking P<0.05 as the difference had statistical significance. The statistical software SPSS 19.ResultThis study retrospectively analyzed the data of 495 cases of Nanfang hospital endocrine Department of Neurosurgery nonfunctional pituitary adenoma and craniopharyngioma patients. Non functional pituitary adenoma tissues and 10 cases of craniopharyngioma tumor tissue specimens and corresponding peripheral blood and cell culture samples were detected in 25 cases of inflammatory factor, endocrine and collect corresponding data.1. The hypopituitarism characteristics of craniopharyngioma1.1 This study a total of 264 patients with craniopharyngioma patients,235 cases (89%) appearance of pituitary hypofunction. Among the different age groups and between the surgical classification of pituitary dysfunction rate compared with significant difference (P<0.05). Different gender, pathological type, tumor size and there is no cystic change, there was no significant difference in the comparison between the calcification (P>0.05). In the presence of hypopituitarism patients,64 cases of the pituitary dysfunction,171 cases of patients with pituitary hypofunction.1.2 different age groups of hypopituitarism comparison of different age groups the incidence of pituitary hypofunction patients, in patients with hypopituitarism, children group had panhypopituitarism ratio was significantly higher than that of adult group (P=0.028). The function of the shaft, GH axis dysfunction in children group and adult frequency had significant difference between groups (P<0.05), while the other axis had no significant difference compared with (P>0.05).1.3 according to the maximum diameter of the tumor group, the incidence of pituitary function impairment were compared between the shaft and the number of axis hormone deficiency. In addition to the GH axis, the axis dysfunction was not statistically significant (P>0.05), in patients with hypopituitarism, panhypopituitarism number among the groups was statistically significant (P<0.05). Comparison of 1.4 different surgical classification of pituitary hypothyroidism incidence characteristics, appear hypopituitarism patients with gonadal axis, GH axis, thyroid axis and the cortisol axis had a significant difference (P<0.05). In patients with hypopituitarism, panhypopituitarism incidence of Q type>T type>S type, the differences had statistical differences (P<0.05).1.5 comparison of different age group of surgery type distribution, different age groups of Q type and S type had a significant difference (P<0.05), the group of children Q type craniopharyngioma was significantly higher than that in adult group; but there was no difference between the two type T (P>0.05).2 the characteristics of non functional pituitary adenoma of pituitary hypofunction2.1 this study included a total of 231 cases of nonfunctioning pituitary adenomas in patients with initial treatment in our department, including 190 cases (82.3%) appearance of pituitary dysfunction,41 patients with normal pituitary function. Between the two groups in age, tumor size had no significant difference (P>0.05); gender and tumor size packet which also showed no significant difference (P>0.05).2.2. Non-functional pituitary adenoma by different maximal tumor diameter divided into’2cm,2-4cm,4-6cm and 6cm four groups’. Among the groups the prevalence of hypopituitarism, hypothyroidism occurred number function axis and each axis dysfunction rate had no significant difference (P>0.05).3. Comparison of hypopituitarism between Non-functional pituitary adenoma and Q type craniopharyngiomaComparison of the general situation of functional pituitary adenoma and Q type craniopharyngioma, in which non functional pituitary adenoma of pituitary dysfunction occurred in 82.3%, Q type craniopharyngioma is 94.6%. Between the two groups in gender composition also no statistical difference (P>0.05). Between the two groups in tumor size packet structure and hypopituitarism frequency had significant difference (P<0.05).4. Expression of inflammatory factor in tumor4.1. Comparison of 25 cases of nonfunctioning pituitary adenoma specimens of tumor patients,10 cases of craniopharyngioma tumor specimens from patients with clinical cases. Between the two groups in tumor size, gender had no significant difference (P>0.05); no significant difference statistically significant age difference (P<0.05). Comparing the two groups of pituitary dysfunction rate, non functional pituitary adenoma was 64%, craniopharyngioma is 100%, with statistical difference (P<0.05), craniopharyngioma patients with hypopituitarism was significantly higher than that in non functional pituitary adenoma patients. No statistically significant differences between the two groups of hypopituitarism degree (P>0.05).4.2. Comparison of 10 kinds of inflammatory factors expression in craniopharyngiomas and no inflammatory factor of pituitary adenoma tumor tissue function. There was significant difference between two groups (P<0.05) is TNF-alpha, IL-1 alpha, IL-6, IL-8 and MCP-1, these factors in craniopharyngioma samples expression were higher than those of non functional pituitary adenoma. There were no significant differences between the expression of the other 5 factors between the two groups (P>0.05).Conclusion1. According to surgical classification, the incidence of hypopituitarism of craniopharyngioma was characterized by Q>T> S in the preoperative.2. Tumor size can not be used to speculate the occurrence of the hormone deficiency in the preoperative patients with craniopharyngioma and non functional pituitary adenomas. In these patients with craniopharyngioma, tumor size may be associated with the degree and level of preoperative pituitary dysfunction.3. The incidence of pituitary dysfunction in pediatric patients was higher than that in adult patients, and Q type craniopharyngioma was more common in children group.4. The incidence of pituitary dysfunction in Q type craniopharyngioma is higher than that of the pituitary adenomas.5. The inflammatory reaction may be one of the causes of pituitary dysfunction in patients with craniopharyngioma.6. TNF-, IL-1, IL-6, IL-8 and MCP-1 were significantly higher in the tumor tissues of craniopharyngioma than in the pituitary adenomas. |