GH型垂体腺瘤MRI、血内分泌激素与激素免疫组化特点及其相互关系的研究

发布时间：2018-08-03 10:28

【摘要】：目的探讨GH型垂体腺瘤患者MRI、血内分泌激素与激素免疫组化点及其相互关系,初步揭示GH型垂体瘤发病的病理免疫反应机制。方法回顾分析2008年1月~2013年6月我科采用鼻蝶入路显微手术切除的84例GH型垂体腺瘤的临床资料。(1)使用多田公式法(xyz/2)计算肿瘤体积(v);运用免疫化学发光法测定术前基础血内分泌激素水平,术后5天及4周进行血生长激素(GH)动态测定,了解术前术后GH的变化规律,寻求判定肿瘤治愈缓解标准的时间窗;采用免疫组织化学的方法检测腺瘤内各种激素免疫反应阳性细胞,分析肿瘤内分泌激素免疫反应表达规律及其与临床内分泌激素水平、肿瘤生物学行为及肿瘤大小的关系。(2)比较分析继发与不继发糖尿病的GH型垂体瘤患者临床资料的不同,采用二分类多因素Logistic回归分析GH型垂体瘤患者继发糖尿病的相关因素。结果(1)以肢端肥大症为主要临床表现的垂体腺瘤患者无明显性别差异,男:女=1:1,好发于41-50岁的中年人,肢大发病至就诊时间集中在6-10年。GH病理免疫反应平均光密度(AOD)值高于泌乳素(PRL)、促卵泡激素(FSH)、促肾上腺皮质激素(ACTH)、促黄体生成素(LH)(P分别=0.047、0.000、0.000、0.000),GH与促甲状腺激素(TSH)比较差异无统计学意义(P=0.139);肿瘤内分泌激素免疫反应阳性表达数量依次为GH62例(74%)、PRL36例(43%)、TSH23例(27%);常见表达类型依次为GH 23例(27%)、GH+PRL 16例(19%)、PRL+TSH 8例(10%);GH、PRL病理免疫阳性率、血液激素水平升高率及临床表现阳性率分别为74%、99%、100%及43%、15%、10%,差异有统计学意义(x2=27.024,P=0.000);TSH、ACTH、FSH、LH病理免疫阳性率分别为27%、18%、10%、8%,但临床内分泌激素测定均在正常范围内。患者术前、术后5天及术后4周血GH相比差异有统计学意义(F=19.120,P=0.000);术后5天GH[(11.64±5.83)ng/ml]与术前血GH[(51.14±36.01)ng/ml]相比快速下降,差异有统计学意义(P=0.004);术后4周血GH[(5.46±4.25)ng/ml]仍然继续下降,但下降速度变慢,与术后5天血GH下降相比仍有显著性差异(P=0.011)。(2)MRI显示肿瘤可突破鞍膈向鞍上生长、突破鞍底向蝶窦内生长,鞍下侵犯指数[(2.35±0.69)cm]明显高于鞍上侵犯指数[(0.66±0.25)cm],差异有统计学意义(t=16.128,P=0.000)。术前基础血清GH水平[(35.06±26.68)ng/ml]与瘤体大小[(7.98±5.24)cm3]、肿瘤GH免疫反应AOD值(0.395±0.383)相比无明显相关性(分别为r=0.117,P=0.144;r=-0.076,P=0.555),瘤体大小与GH免疫反应AOD值相比亦无明显相关性(r=-0.066,P=0.609)。(3)继发和不继发糖尿病的GH型垂体瘤术前血GH分别为(42.83±8.70)ng/ml、(38.91±36.46)ng/ml(t=5.253,P=0.031);促甲状腺激素(TSH)免疫反应阳性率(70%)明显多于不继发者(14%)(x2=23.971,P=0.000)。Logistic回归分析统计结果显示发病时间、术前血GH水平及TSH免疫阳性Exp(B)和P值分别为0.212、1.160、93.392和0.010、0.004、0.002,Exp(B)最大者为TSH免疫阳性。结论(1)GH型垂体腺瘤MRI表现有明显的向蝶窦内优先侵犯生长的趋势,为该病由影像学诊断向内分泌学功能诊断提供了参考。(2)可以参考术后4周的血GH水平作为评判手术治疗效果的时间窗。(3)GH型垂体腺瘤GH、TSH免疫表达强度均高于其他内分泌激素,GH、TSH、PRL免疫阳性数量多于其它内分泌激素,GH、GH+PRL、PRL+TSH为常见病理免疫反应类型,肿瘤细胞分泌的TSH、PRL参与了肢大患者发病的病理生理过程。(4)GH免疫表达与血内分泌激素水平及临床表现具有良好的相符性,但GH术前基础血水平、病理免疫反应强度及瘤体大小之间无明显相关性,反应了GH型垂体腺瘤病理免疫反应与血内分泌激素水平及影像学表现之间既相互联系又错综复杂的关系。(5)肿瘤发病时间、术前血GH水平及TSH免疫阳性是GH型垂体瘤继发糖尿病的相关因素,肿瘤TSH免疫阳性是主要因素,肿瘤分泌的TSH参与了GH型垂体瘤继发糖尿病的病理生理过程,具体的调控机制尚待进一步深入研究。对于TSH免疫阳性的GH型垂体瘤患者既要关注其发展为糖尿病的可能,又要加强随访,关注其发展为恶性肿瘤的可能,以达到对该病的早期发现及诊治。
[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.
【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R736.4

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