發(fā)布時間：2018-08-03 10:28

【摘要】：目的探討GH型垂體腺瘤患者MRI、血內分泌激素與激素免疫組化點及其相互關系,初步揭示GH型垂體瘤發(fā)病的病理免疫反應機制。方法回顧分析2008年1月~2013年6月我科采用鼻蝶入路顯微手術切除的84例GH型垂體腺瘤的臨床資料。(1)使用多田公式法(xyz/2)計算腫瘤體積(v);運用免疫化學發(fā)光法測定術前基礎血內分泌激素水平,術后5天及4周進行血生長激素(GH)動態(tài)測定,了解術前術后GH的變化規(guī)律,尋求判定腫瘤治愈緩解標準的時間窗;采用免疫組織化學的方法檢測腺瘤內各種激素免疫反應陽性細胞,分析腫瘤內分泌激素免疫反應表達規(guī)律及其與臨床內分泌激素水平、腫瘤生物學行為及腫瘤大小的關系。(2)比較分析繼發(fā)與不繼發(fā)糖尿病的GH型垂體瘤患者臨床資料的不同,采用二分類多因素Logistic回歸分析GH型垂體瘤患者繼發(fā)糖尿病的相關因素。結果(1)以肢端肥大癥為主要臨床表現的垂體腺瘤患者無明顯性別差異,男:女=1:1,好發(fā)于41-50歲的中年人,肢大發(fā)病至就診時間集中在6-10年。GH病理免疫反應平均光密度(AOD)值高于泌乳素(PRL)、促卵泡激素(FSH)、促腎上腺皮質激素(ACTH)、促黃體生成素(LH)(P分別=0.047、0.000、0.000、0.000),GH與促甲狀腺激素(TSH)比較差異無統(tǒng)計學意義(P=0.139);腫瘤內分泌激素免疫反應陽性表達數量依次為GH62例(74%)、PRL36例(43%)、TSH23例(27%);常見表達類型依次為GH 23例(27%)、GH+PRL 16例(19%)、PRL+TSH 8例(10%);GH、PRL病理免疫陽性率、血液激素水平升高率及臨床表現陽性率分別為74%、99%、100%及43%、15%、10%,差異有統(tǒng)計學意義(x2=27.024,P=0.000);TSH、ACTH、FSH、LH病理免疫陽性率分別為27%、18%、10%、8%,但臨床內分泌激素測定均在正常范圍內�；颊咝g前、術后5天及術后4周血GH相比差異有統(tǒng)計學意義(F=19.120,P=0.000);術后5天GH[(11.64±5.83)ng/ml]與術前血GH[(51.14±36.01)ng/ml]相比快速下降,差異有統(tǒng)計學意義(P=0.004);術后4周血GH[(5.46±4.25)ng/ml]仍然繼續(xù)下降,但下降速度變慢,與術后5天血GH下降相比仍有顯著性差異(P=0.011)。(2)MRI顯示腫瘤可突破鞍膈向鞍上生長、突破鞍底向蝶竇內生長,鞍下侵犯指數[(2.35±0.69)cm]明顯高于鞍上侵犯指數[(0.66±0.25)cm],差異有統(tǒng)計學意義(t=16.128,P=0.000)。術前基礎血清GH水平[(35.06±26.68)ng/ml]與瘤體大小[(7.98±5.24)cm3]、腫瘤GH免疫反應AOD值(0.395±0.383)相比無明顯相關性(分別為r=0.117,P=0.144;r=-0.076,P=0.555),瘤體大小與GH免疫反應AOD值相比亦無明顯相關性(r=-0.066,P=0.609)。(3)繼發(fā)和不繼發(fā)糖尿病的GH型垂體瘤術前血GH分別為(42.83±8.70)ng/ml、(38.91±36.46)ng/ml(t=5.253,P=0.031);促甲狀腺激素(TSH)免疫反應陽性率(70%)明顯多于不繼發(fā)者(14%)(x2=23.971,P=0.000)。Logistic回歸分析統(tǒng)計結果顯示發(fā)病時間、術前血GH水平及TSH免疫陽性Exp(B)和P值分別為0.212、1.160、93.392和0.010、0.004、0.002,Exp(B)最大者為TSH免疫陽性。結論(1)GH型垂體腺瘤MRI表現有明顯的向蝶竇內優(yōu)先侵犯生長的趨勢,為該病由影像學診斷向內分泌學功能診斷提供了參考。(2)可以參考術后4周的血GH水平作為評判手術治療效果的時間窗。(3)GH型垂體腺瘤GH、TSH免疫表達強度均高于其他內分泌激素,GH、TSH、PRL免疫陽性數量多于其它內分泌激素,GH、GH+PRL、PRL+TSH為常見病理免疫反應類型,腫瘤細胞分泌的TSH、PRL參與了肢大患者發(fā)病的病理生理過程。(4)GH免疫表達與血內分泌激素水平及臨床表現具有良好的相符性,但GH術前基礎血水平、病理免疫反應強度及瘤體大小之間無明顯相關性,反應了GH型垂體腺瘤病理免疫反應與血內分泌激素水平及影像學表現之間既相互聯系又錯綜復雜的關系。(5)腫瘤發(fā)病時間、術前血GH水平及TSH免疫陽性是GH型垂體瘤繼發(fā)糖尿病的相關因素,腫瘤TSH免疫陽性是主要因素,腫瘤分泌的TSH參與了GH型垂體瘤繼發(fā)糖尿病的病理生理過程,具體的調控機制尚待進一步深入研究。對于TSH免疫陽性的GH型垂體瘤患者既要關注其發(fā)展為糖尿病的可能,又要加強隨訪,關注其發(fā)展為惡性腫瘤的可能,以達到對該病的早期發(fā)現及診治。
[Abstract]:Objective to investigate the relationship between MRI, serum endocrine hormones and hormone immunization points in patients with GH pituitary adenoma, and to reveal the mechanism of pathological immune response to the pathogenesis of GH pituitary adenoma. Methods the clinical data of 84 cases of GH pituitary adenoma removed by transsphenoidal microsurgery in June of January 2008 in our department were reviewed and analyzed. (1) the use of multiple fields. The tumor volume (V) was calculated by the formula method (xyz/2); the level of basal blood endocrine hormone before operation was measured by immunoluminescence. The dynamic measurement of blood growth hormone (GH) was carried out at 5 and 4 weeks after operation to find out the changes in the changes of GH before and after the operation, to find the time window to determine the remission standard of the tumor, and to detect the internal adenoma by immunohistochemical method. The expression of endocrine hormone immunoreaction and its relationship with the level of endocrine hormone, tumor biological behavior and tumor size were analyzed. (2) the difference of clinical data between secondary and non secondary diabetes patients with GH pituitary adenoma was compared and analyzed by two classification multiple factor Logistic regression analysis. The related factors of secondary diabetes in patients with type GH pituitary tumor. Results (1) there was no significant gender difference in pituitary adenoma in acromegalomattic symptoms, male: female =1:1, good for 41-50 year old middle-aged people, and the time of large onset of limb was concentrated in 6-10 years.GH pathological immune response mean light density (AOD) was higher than prolactin (PRL), promoting ovulation. Hormone (FSH), adrenocorticotropin (ACTH), luteinizing hormone (LH) (P =0.047,0.000,0.000,0.000), GH and thyroid stimulating hormone (TSH) had no significant difference (P=0.139), and the number of positive expressions of endocrine hormone immunoreaction was GH62 (74%), PRL36 (43%), TSH23 (27%), and the common expression type was G. H 23 cases (27%), GH+PRL 16 cases (19%), PRL+TSH 8 cases (10%); GH, PRL pathological immunological positive rate, blood hormone level increase rate and clinical manifestation positive rate were 74%, 99%, 100% and 43%, 15%, 10%, the difference was statistically significant (x2=27.024, P=0.000); TSH, ACTH, FSH, LH pathological immunological positive rates were respectively 27%, 18%, but clinical endocrine hormone determination, but clinical endocrine hormone determination, but clinical endocrine hormone determination, but clinical endocrine hormone determination, but clinical endocrine hormone determination, but clinical hormone determination but, but clinical endocrine hormone determination The difference between the 5 days and 4 weeks after operation was statistically significant (F=19.120, P=0.000), and GH[(11.64 + 5.83) ng/ml] and GH[(51.14 + 36.01) ng/ml] before the operation decreased rapidly after operation, and the difference was statistically significant (P=0.004), and the blood GH[(5.46 + 4.25) ng/ml] still continued to decline, but decreased at 4 weeks after the operation. There was a significant difference between the 5 days after the operation and the 5 days after the operation (P=0.011). (2) MRI showed that the tumor could break through the sellar diaphragm to the saddle, break through the saddle bottom to the sphenoidal sinus, and the infrasellar invasion index [(2.35 + 0.69) cm] was significantly higher than the suprasellar invasion index [(0.66 + 0.25) cm], t=16.128, P=0.000). There was no significant correlation between the tumor size [(35.06 + 26.68)] ng/ml] and the tumor size [(7.98 + 5.24) cm3]] and the AOD value of the tumor GH (0.395 + 0.383) (r=0.117, P=0.144; r=-0.076, P=0.555). The size of the tumor had no significant correlation with the AOD value of the GH immune response (r=-0.066, P=0.609). (3) secondary and non diabetic pituitary adenomas The blood GH was (42.83 + 8.70) ng/ml, (38.91 + 36.46) ng/ml (t=5.253, P=0.031), and the positive rate of thyroid stimulating hormone (TSH) immunoreaction (70%) was more than that of those without secondary (14%) (x2=23.971, P=0.000). The statistical results of.Logistic regression analysis showed the onset time. The level of GH and TSH immunoreactive Exp and 0. were 0. and 0., respectively. 010,0.004,0.002, Exp (B) is the largest TSH immunoreactive. Conclusion (1) the MRI manifestations of GH pituitary adenoma have obvious tendency towards the first invasion of the sphenoidal sinus, which provides a reference for the diagnosis of the disease from the imaging diagnosis to the endocrinological function diagnosis. (2) the blood GH level of 4 weeks after the operation can be used as a time window for evaluating the effect of the surgical treatment. (3) GH type Pituitary adenoma GH, TSH immune expression intensity is higher than other endocrine hormones, GH, TSH, PRL immunoreactive number more than other endocrine hormones, GH, GH+PRL, PRL+TSH as the common pathological type of immune response, the tumor cells secreted TSH, PRL involved in the disease of patients with limb and physiology and physiology. (4) GH immune expression and blood endocrine hormone levels and levels The clinical manifestations were well consistent, but there was no significant correlation between the basic blood level of GH before operation, the intensity of pathological immune response and the size of the tumor. The relationship between the pathological immune response of GH type pituitary adenoma and the level of endocrine hormone and the imaging findings was interrelated and complex. (5) the time of the tumor and the blood GH water before the operation. The positive TSH immunoreaction is the related factor of secondary diabetes in GH type pituitary tumor. The immunoreactive TSH is the main factor. The TSH secreted by the tumor is involved in the pathophysiological process of the secondary diabetes of the GH pituitary tumor. The specific regulatory mechanism remains to be further studied. The development of the GH type pituitary tumor patients with TSH immunologically positive should be concerned with their development. For the possibility of diabetes mellitus, follow-up should be strengthened to pay attention to the possibility of its development into malignant tumors, so as to achieve the early detection and diagnosis of the disease.
【學位授予單位】：青島大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R736.4

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