垂体生长激素腺瘤合并糖尿病回顾性临床分析
|
摘要
目的：分析与GH腺瘤患者糖尿病发病率有关的因素，经蝶手术对GH腺瘤及其合并糖尿病的治疗效果以及影响治疗效果的因素。
方法：回顾性分析GH腺瘤病例197例，根据是否合并糖尿病分为两个组，其中合并糖尿病组83例，无糖尿病组114例。将GH腺瘤合并糖尿病组与无糖尿病组患者的年龄、病程、GH值进行对比，分析其与GH腺瘤患者糖尿病发病率的关系；将所有的GH腺瘤根据肿瘤大小、侵袭性进行分组，比较各组的糖尿病发病率，分析肿瘤大小、侵袭性与GH腺瘤患者糖尿病发病率的关系；将GH腺瘤合并糖尿病组，根据肿瘤的大小、侵袭性、术前的GH值进行分组，术后复查GH及血糖值，与术前对比评价经蝶手术疗效，分析影响GH腺瘤及糖尿病治疗效果的因素。
结果：
(1)合并糖尿病组与无糖尿病组的GH腺瘤患者发病年龄、病程、GH值，存在统计学差异；微腺瘤、大腺瘤、巨大腺瘤的糖尿病发病率无统计学差异；侵袭性腺瘤与非侵袭性腺瘤糖尿病的发病率无统计学差异。
(2) GH腺瘤合并糖尿病患者术后GH腺瘤治愈及缓解率为67.5％；微腺瘤、大腺瘤、巨大腺瘤治愈及缓解率分别为81.3％、70.8％、47.4％；侵袭性腺瘤组和非侵袭性腺瘤组治愈及缓解率分别为42.9％、75.8％；术前GH≤50μg/L和GH＞50μg/L组治愈及缓解率分别为75.9％、51.7％。微腺瘤与巨大腺瘤治愈及缓解率有统计学差异；微腺瘤与大腺瘤以及大腺瘤与巨大腺瘤治愈及缓解率无统计学差异；侵袭性腺瘤与非侵袭性腺瘤，术前GH≤50μg/L和GH＞50μg/L组，治愈缓解率有统计学差异。
(3) GH腺瘤合并糖尿病患者术后总体血糖达到一般控制标准以上55例，占66.3％。微腺瘤、大腺瘤、巨大腺瘤组血糖达到一般控制以上标准分别为87.5％、68.8％、47.4％；侵袭性腺瘤组和非侵袭性腺瘤组血糖达到一般控制以上标准分别为47.6％、72.6％；术前GH≤50μg/L和GH＞50μg/L组血糖达到一般控制以上标准分别为75.6％、52.9％；GH腺瘤治愈缓解组与未缓解组血糖达到一般控制以上标准分别为85.7％、25.9％。微腺瘤与巨大腺瘤术后血糖改善情况有统计学差异，微腺瘤与大腺瘤以及大腺瘤与巨大腺瘤术后血糖改善情况无统计学差异；侵袭性腺瘤与非侵袭性腺瘤，术前GH≤50μg/L和GH＞50μg/L组，术后血糖改善情况有统计学差异；GH腺瘤治愈缓解组与未缓解组血糖改善情况有显著差异。
结论：
(1) GH腺瘤患者糖尿病的发病率，主要与发病年龄、病程、GH值相关，与肿瘤的大小、侵袭性无关。
(2)经蝶手术GH腺瘤的治愈及缓解率比较高，GH腺瘤的治愈及缓解率与肿瘤的大小、侵袭性、术前的GH水平有关。
(3) GH腺瘤所合并糖尿病的治疗效果归根结底取决于GH腺瘤的治疗效果，通过经蝶手术切除GH腺瘤，达到治愈或缓解，进而能够有效的控制血糖。
OBJECTIVE: To investigate the correlative factors influencing the incidence of diabetes mellitus(DM) of GH secreting adenoma,analyse the curative effect of transphenoidal surgery and the correlative factors influencing the effect.
METHODS : Review the clinical data of 197 cases of GH secreting adenoma,which were divided into two groups ,one group (83 cases) was with DM ,another group (114 cases) was without DM. Compare the age ,course of disease and GH levels of the two groups in order to analyse the factors influencing the incidence of DM.A11 the patients were classified according to tumor size ,invasive .Analyse their influencing effects to the incidence of DM. The group with DM was classified according to tumor size, preoperative GH level and invasive.Exam the GH and blood glucose(BG) level postoperative ..compared with the GH and BG level preoperative, evaluate the curative effect of transphenoidal surgery .Analyse the correlative factors influencing the curative effect of GH secreting adenoma and DM.
RESULTS:
(1)There are statistical significance in difference of the age ,course of disease ,GH level between GH secreting adenoma with DM and GH secreting adenoma without DM .There are no statistical significance in difference of the incidence of DM between different size of tumors ,invasive tumors and non-invasive tumors.
(2)The total rates of cure and remission of GH secreting adenoma were 67.5%, and the cure and remission rates of microadenomas,macroadenomas and giant adenomas were 81.3%, 70.8% and 47.4% respectively. The cure and remission rates of invasive adenomas and noninvasive adenomas were 42.9% and 75.8% respectively.The rates of cure and remission of GH≤50μg /L group and GH>50μg /L group were 75.9% and 51.7% respectively .There are statistical significance in difference of the cure and remission rates between microadenomas and giant adenomas , invasive adenomas and noninvasive adenomas,different GH level groups preoperative. There are no statistical significance in difference of the cure and remission rates between microadenomas and macroadenomas, macroadenomas and giant adenomas.
(3)The total rates of BG level achieved or exceeded general controlled level is 66.3% postoperative .The rates of BG level achieved or exceeded general controlled level of microadenomas,macroadenomas and giant adenomas are 87.5%,68.8% and 47.4% respectively;of invasive adenomas and noninvasive adenomas are 47.6% and 72.6% respectively;of GH≤50μg /L group and GH＞50μg /L group are 75.6% and 52.9% respectively;of GH secreting adenomas which have been controlled and those have not been controlled are 85.7%、25.9% respectively.The curative results of DM between microadenomas and giant adenomas, invasive adenomas and noninvasive adenomas,different GH level preoperative groups have statistical difference and there are no statistical difference of the curative results between microadenomas and macroadenomas, macroadenomas and giant adenomas.There are great statistical difference of curative results between GH secreting adenomas which have been controlled and those have not been controlled.
CONCLUSION:
(1)The DM incidence of GH secreting adenoma are correlated with the age,course of disease ,GH level.
(2) The cure and remission rates of GH secreting adenoma by transphenoidal surgery is very high and it is mainly correlated with the tumor size,invasive,GH level preoperative.
(3) The curative effect of DM is mainly correlated with the curative effect of GH secreting adenoma. While the GH level was reduced by transphenoidal surgery,the DM could be better controlled.
方法：回顾性分析GH腺瘤病例197例，根据是否合并糖尿病分为两个组，其中合并糖尿病组83例，无糖尿病组114例。将GH腺瘤合并糖尿病组与无糖尿病组患者的年龄、病程、GH值进行对比，分析其与GH腺瘤患者糖尿病发病率的关系；将所有的GH腺瘤根据肿瘤大小、侵袭性进行分组，比较各组的糖尿病发病率，分析肿瘤大小、侵袭性与GH腺瘤患者糖尿病发病率的关系；将GH腺瘤合并糖尿病组，根据肿瘤的大小、侵袭性、术前的GH值进行分组，术后复查GH及血糖值，与术前对比评价经蝶手术疗效，分析影响GH腺瘤及糖尿病治疗效果的因素。
结果：
(1)合并糖尿病组与无糖尿病组的GH腺瘤患者发病年龄、病程、GH值，存在统计学差异；微腺瘤、大腺瘤、巨大腺瘤的糖尿病发病率无统计学差异；侵袭性腺瘤与非侵袭性腺瘤糖尿病的发病率无统计学差异。
(2) GH腺瘤合并糖尿病患者术后GH腺瘤治愈及缓解率为67.5％；微腺瘤、大腺瘤、巨大腺瘤治愈及缓解率分别为81.3％、70.8％、47.4％；侵袭性腺瘤组和非侵袭性腺瘤组治愈及缓解率分别为42.9％、75.8％；术前GH≤50μg/L和GH＞50μg/L组治愈及缓解率分别为75.9％、51.7％。微腺瘤与巨大腺瘤治愈及缓解率有统计学差异；微腺瘤与大腺瘤以及大腺瘤与巨大腺瘤治愈及缓解率无统计学差异；侵袭性腺瘤与非侵袭性腺瘤，术前GH≤50μg/L和GH＞50μg/L组，治愈缓解率有统计学差异。
(3) GH腺瘤合并糖尿病患者术后总体血糖达到一般控制标准以上55例，占66.3％。微腺瘤、大腺瘤、巨大腺瘤组血糖达到一般控制以上标准分别为87.5％、68.8％、47.4％；侵袭性腺瘤组和非侵袭性腺瘤组血糖达到一般控制以上标准分别为47.6％、72.6％；术前GH≤50μg/L和GH＞50μg/L组血糖达到一般控制以上标准分别为75.6％、52.9％；GH腺瘤治愈缓解组与未缓解组血糖达到一般控制以上标准分别为85.7％、25.9％。微腺瘤与巨大腺瘤术后血糖改善情况有统计学差异，微腺瘤与大腺瘤以及大腺瘤与巨大腺瘤术后血糖改善情况无统计学差异；侵袭性腺瘤与非侵袭性腺瘤，术前GH≤50μg/L和GH＞50μg/L组，术后血糖改善情况有统计学差异；GH腺瘤治愈缓解组与未缓解组血糖改善情况有显著差异。
结论：
(1) GH腺瘤患者糖尿病的发病率，主要与发病年龄、病程、GH值相关，与肿瘤的大小、侵袭性无关。
(2)经蝶手术GH腺瘤的治愈及缓解率比较高，GH腺瘤的治愈及缓解率与肿瘤的大小、侵袭性、术前的GH水平有关。
(3) GH腺瘤所合并糖尿病的治疗效果归根结底取决于GH腺瘤的治疗效果，通过经蝶手术切除GH腺瘤，达到治愈或缓解，进而能够有效的控制血糖。
OBJECTIVE: To investigate the correlative factors influencing the incidence of diabetes mellitus(DM) of GH secreting adenoma,analyse the curative effect of transphenoidal surgery and the correlative factors influencing the effect.
METHODS : Review the clinical data of 197 cases of GH secreting adenoma,which were divided into two groups ,one group (83 cases) was with DM ,another group (114 cases) was without DM. Compare the age ,course of disease and GH levels of the two groups in order to analyse the factors influencing the incidence of DM.A11 the patients were classified according to tumor size ,invasive .Analyse their influencing effects to the incidence of DM. The group with DM was classified according to tumor size, preoperative GH level and invasive.Exam the GH and blood glucose(BG) level postoperative ..compared with the GH and BG level preoperative, evaluate the curative effect of transphenoidal surgery .Analyse the correlative factors influencing the curative effect of GH secreting adenoma and DM.
RESULTS:
(1)There are statistical significance in difference of the age ,course of disease ,GH level between GH secreting adenoma with DM and GH secreting adenoma without DM .There are no statistical significance in difference of the incidence of DM between different size of tumors ,invasive tumors and non-invasive tumors.
(2)The total rates of cure and remission of GH secreting adenoma were 67.5%, and the cure and remission rates of microadenomas,macroadenomas and giant adenomas were 81.3%, 70.8% and 47.4% respectively. The cure and remission rates of invasive adenomas and noninvasive adenomas were 42.9% and 75.8% respectively.The rates of cure and remission of GH≤50μg /L group and GH>50μg /L group were 75.9% and 51.7% respectively .There are statistical significance in difference of the cure and remission rates between microadenomas and giant adenomas , invasive adenomas and noninvasive adenomas,different GH level groups preoperative. There are no statistical significance in difference of the cure and remission rates between microadenomas and macroadenomas, macroadenomas and giant adenomas.
(3)The total rates of BG level achieved or exceeded general controlled level is 66.3% postoperative .The rates of BG level achieved or exceeded general controlled level of microadenomas,macroadenomas and giant adenomas are 87.5%,68.8% and 47.4% respectively;of invasive adenomas and noninvasive adenomas are 47.6% and 72.6% respectively;of GH≤50μg /L group and GH＞50μg /L group are 75.6% and 52.9% respectively;of GH secreting adenomas which have been controlled and those have not been controlled are 85.7%、25.9% respectively.The curative results of DM between microadenomas and giant adenomas, invasive adenomas and noninvasive adenomas,different GH level preoperative groups have statistical difference and there are no statistical difference of the curative results between microadenomas and macroadenomas, macroadenomas and giant adenomas.There are great statistical difference of curative results between GH secreting adenomas which have been controlled and those have not been controlled.
CONCLUSION:
(1)The DM incidence of GH secreting adenoma are correlated with the age,course of disease ,GH level.
(2) The cure and remission rates of GH secreting adenoma by transphenoidal surgery is very high and it is mainly correlated with the tumor size,invasive,GH level preoperative.
(3) The curative effect of DM is mainly correlated with the curative effect of GH secreting adenoma. While the GH level was reduced by transphenoidal surgery,the DM could be better controlled.
引文
1．王忠诚．王忠诚神经外科学．湖北科学技术出版社．2005：620-651
2. KreutzeR, JurgeN, FahlbuscH, eta.l Diagnosis and treatment of pituitary tumors[J]. Current Opinion in Neurology, 2004; 17 (6):693-703
3. Kreutze J, Vance ML, Lopes MB, Laws ER. Surgical management of GH-secreting pituitary adenomas an outcome study using modem remission criteria. J. Clin Endocrinol Metab. 2001; 86: 4072-4077
4. Brada M, etal. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol Metab. 1993; 38: 571-578
5. Carrasco C, Veliz J, Rojas D, Wohllk N. Result of surgical treatment for acromegaly in 53 patients. Rev Med Chil. 2006; 134(8):989-996
6．王天华，陈书达，朱君明等．垂体生长激素腺瘤显微手术治疗．肿瘤学杂志．2006：12(2)124-125
7. Laws ER, Vance ML, Thapar K. Pituitary surgery for the management of acromegaly. Horm Res. 2000; 53(suppl 3): 71-75
8. NomiKos P, Buchfelder M, Fahlbusch R. The outcom of surgery in 668 patients with acromegaly using current criteria of biochemical cure[J]. Eur J Endocrinol. 2005; 152(3):379-387
9．王志勇，雷霆．肢端肥大症的综合治疗．实用医学杂志．2006：22(12)：1467-1468
10. Colao A, Ferone D, Marzulp P, et al. Effect of different dopaminergic agents in the treatm ent of acromegaly. J Clin Endocrinol Metab. 1997. 82: 518-523.
11. Papadakis ED, Nicklin SA, BakerAH, et a.l Promoters and control elements: desinging expression cassettes for gene therapy[J]. Cur-rentGene Therapy, 2004, 4(1): 89-113.
12. Colao A, Vitale G, Cappabianca P, et al. Outcome of cabergoline treatment in men with prolactinoma: Effects of a 24-month treatment on prolactin levels tumor mass, recovery of pituitary funciton, and semen anaylysis[J]. J Clin Endocrinnol Metab, 2004, 89(4): 1704-1711.
13. Abs R, Verhelst J Maiter D, etal. Cabergoline In the Treatment of Acromegaly: A Study in 64 Patients.J Clin Endocrinol Metab.l998;83(2):374-378
14. Hofland LJ,Lanberts SW.The Pathophysiological Conseqences of Somatostatin Receptor Internalization and Resistance.Endocr Rev.2003;24(l):28-47
15. Bevan JS,Atkinson AB,et al.Primary Medical Therapy for Acromegaly:An open,prospective,multicentre study of the effects of Subcutaneous and Intramuscular Slow-release Octreotide on Growth Hormone,Insulin -like Growth factor-l,and Tumor Size.J Clin Endocrinol Metab.2002;87(10):4554-4563
16. Ballare E,Persani L,Lania AG,et al.Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treat-ment.J Clin Endocrinol Metab.2001;86:3809-381
17. Newman CB, Melmed S, George A, et al. Octreotide as primary therapy for acromegaly [J]. J Endocrinol Metab, 1998, 83(9): 3034-3040
18. Colao A, Ferone D, Marzullo P, Lombardi G 2004 Systemic complications of acromegaly: epidemiology, pathogenesis and management. Endocr Rev.2004;25:102-152
19. Cozzi, Renato; Montini, Marcella; Attanasio, Roberto,et al. Primary treatment of acromegaly withoctreotide LAR: A long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. The Endocrine Society.2006;91(4): 1397-1403
20. Patel YC,Shereen E,Chick CL,et .Guidelines for the diagnosis and treatment of acromegaly:a Canadian perspective[J]. Clin Invest Med, 2000; 23(3): 172-187
21. Schreiber I,Buchfelder M, Droste M, etal.Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical pratice:Safety and efficacy evaluation from the German Pegvisomant Observation Study.Eur J Endorino.2007; 156(1):75-82
22. Van der Lely AJ, Muler AF. Janssen JA. Control of tumor size and disease activity during cotreatment with octreotide and the growth hormone receptor antagonist pegvisomant in an acromegalic patient. J Clin Endoerinol Metab,2001; 6: 478-481
23. Heaney Anthony P,Fernando Manory,Melmed Shlomo. PPAR- Y Receptor Ligands: Novel Therapy For Pituitary Adenomas. The American Society2003;111(9):1381-1388
24. Racine MS, Barkan AL. Medical management of growth hormone-secreting pituitary adenomas[J]. Pituitary, 2002; 5(2): 67-76.
25．李杰，史继新，王汉东等．α-干扰素和溴隐亭对垂体生长激素腺瘤细胞的作用．中华神经外科杂志．2004；20(3)：207-210
26. Patel YC, Shereen E, Chick CL, et. Guidelines for the diagnosis and treatment of acromegaly: a Canadian perspective[J]. Clin Invest Med, 2000; 23(3): 172-187
27. Melmed S, Vance ML, Barkan AL, et. Current status and future opportunities for controlling acromegaly[J]. Pituitary, 2002; 5(3): 185-196
28. Barkan AL Radiotherapy in acromegaly: the argument against. Clin Endocri-nol (Oxf). 2003; 58:132-135
29. Ganz JC. Gamma knife treatment of pituitary denomas [J]. Stereotact Funct Neurosurg, 1993, 64(Suppl 1): 3-10
30．刘云廷．垂体腺瘤的研究进展[J]．北京军区医药，2000；12(4)：252-254
31. Castinetti FR, Taieb DA, Kuhn JM, et al. Outcome of Gamma Knife Radiosurgery in 82 Patient with Acromegaly: Correlation with Initial Hypersecretion[J]. J Clin Endocrinol Metabol. 2005; 90(8): 4483-4488
32. Gutt B, Wowra B, Alexandrov R, et al. Gamma-knife surgery Is Effective In Normalising Plasma Insulin-like Growth Factor-1 In Patient With Acromegaly [J]. Exp Clin Endocrinol Diabetes. 2005; 113(4): 219-224
33. Lee EJ, Anderson LM, Thimmapaya B, et al. Targeted expression of toxic fenes directed by pituitary hormone promoters: a potential atrategy for adenovirus -mediated genetherapy of pituitary tumors [J]. J Clin Endocrinol Metab,1999, 84(2): 786～794
34．范月超，张洪涛，王雄伟等．抑制pit-1基因表达对垂体生长激素腺瘤生物学行为影响的实验研究．实用医学杂志．2005；21(23)：2597-2600
35. Zhang X, Horwitz GA, Heaney AP, etal. Pituitary tumor transforming gene (PTTG)expression in pituitary adenomas [J]. J Clin Endocrinol Metab, 1999; 84(2): 761-767.
36. Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'. 2005; Eur J Endocrinol 152:379-387
37．马驰原，史继新．垂体腺瘤的基因治疗．中华神经医学杂志．2005；4(8)：855-857
38．朱涛，杨树源．肢端肥大症的药物治疗．中华神经外科杂志．2005：21(3)：188-190
39．胡吉．垂体瘤的内科治疗．国外医学内分泌分册．2005；25(4)：272-274
40．王雄伟．Pegvisomant研究现状及其在肢端肥大症中的应用．中国临床神经外科杂志．2004：9(4)：312-315
41．邵倩．垂体瘤治疗与内分泌反应．国际肿瘤学杂志．2006；33(4)：274-276
42．张正善，丁学华．垂体生长激素腺瘤的治疗进展．中国微侵袭神经外科杂志．2005；10(5)：233-235
2. KreutzeR, JurgeN, FahlbuscH, eta.l Diagnosis and treatment of pituitary tumors[J]. Current Opinion in Neurology, 2004; 17 (6):693-703
3. Kreutze J, Vance ML, Lopes MB, Laws ER. Surgical management of GH-secreting pituitary adenomas an outcome study using modem remission criteria. J. Clin Endocrinol Metab. 2001; 86: 4072-4077
4. Brada M, etal. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol Metab. 1993; 38: 571-578
5. Carrasco C, Veliz J, Rojas D, Wohllk N. Result of surgical treatment for acromegaly in 53 patients. Rev Med Chil. 2006; 134(8):989-996
6．王天华，陈书达，朱君明等．垂体生长激素腺瘤显微手术治疗．肿瘤学杂志．2006：12(2)124-125
7. Laws ER, Vance ML, Thapar K. Pituitary surgery for the management of acromegaly. Horm Res. 2000; 53(suppl 3): 71-75
8. NomiKos P, Buchfelder M, Fahlbusch R. The outcom of surgery in 668 patients with acromegaly using current criteria of biochemical cure[J]. Eur J Endocrinol. 2005; 152(3):379-387
9．王志勇，雷霆．肢端肥大症的综合治疗．实用医学杂志．2006：22(12)：1467-1468
10. Colao A, Ferone D, Marzulp P, et al. Effect of different dopaminergic agents in the treatm ent of acromegaly. J Clin Endocrinol Metab. 1997. 82: 518-523.
11. Papadakis ED, Nicklin SA, BakerAH, et a.l Promoters and control elements: desinging expression cassettes for gene therapy[J]. Cur-rentGene Therapy, 2004, 4(1): 89-113.
12. Colao A, Vitale G, Cappabianca P, et al. Outcome of cabergoline treatment in men with prolactinoma: Effects of a 24-month treatment on prolactin levels tumor mass, recovery of pituitary funciton, and semen anaylysis[J]. J Clin Endocrinnol Metab, 2004, 89(4): 1704-1711.
13. Abs R, Verhelst J Maiter D, etal. Cabergoline In the Treatment of Acromegaly: A Study in 64 Patients.J Clin Endocrinol Metab.l998;83(2):374-378
14. Hofland LJ,Lanberts SW.The Pathophysiological Conseqences of Somatostatin Receptor Internalization and Resistance.Endocr Rev.2003;24(l):28-47
15. Bevan JS,Atkinson AB,et al.Primary Medical Therapy for Acromegaly:An open,prospective,multicentre study of the effects of Subcutaneous and Intramuscular Slow-release Octreotide on Growth Hormone,Insulin -like Growth factor-l,and Tumor Size.J Clin Endocrinol Metab.2002;87(10):4554-4563
16. Ballare E,Persani L,Lania AG,et al.Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treat-ment.J Clin Endocrinol Metab.2001;86:3809-381
17. Newman CB, Melmed S, George A, et al. Octreotide as primary therapy for acromegaly [J]. J Endocrinol Metab, 1998, 83(9): 3034-3040
18. Colao A, Ferone D, Marzullo P, Lombardi G 2004 Systemic complications of acromegaly: epidemiology, pathogenesis and management. Endocr Rev.2004;25:102-152
19. Cozzi, Renato; Montini, Marcella; Attanasio, Roberto,et al. Primary treatment of acromegaly withoctreotide LAR: A long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. The Endocrine Society.2006;91(4): 1397-1403
20. Patel YC,Shereen E,Chick CL,et .Guidelines for the diagnosis and treatment of acromegaly:a Canadian perspective[J]. Clin Invest Med, 2000; 23(3): 172-187
21. Schreiber I,Buchfelder M, Droste M, etal.Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical pratice:Safety and efficacy evaluation from the German Pegvisomant Observation Study.Eur J Endorino.2007; 156(1):75-82
22. Van der Lely AJ, Muler AF. Janssen JA. Control of tumor size and disease activity during cotreatment with octreotide and the growth hormone receptor antagonist pegvisomant in an acromegalic patient. J Clin Endoerinol Metab,2001; 6: 478-481
23. Heaney Anthony P,Fernando Manory,Melmed Shlomo. PPAR- Y Receptor Ligands: Novel Therapy For Pituitary Adenomas. The American Society2003;111(9):1381-1388
24. Racine MS, Barkan AL. Medical management of growth hormone-secreting pituitary adenomas[J]. Pituitary, 2002; 5(2): 67-76.
25．李杰，史继新，王汉东等．α-干扰素和溴隐亭对垂体生长激素腺瘤细胞的作用．中华神经外科杂志．2004；20(3)：207-210
26. Patel YC, Shereen E, Chick CL, et. Guidelines for the diagnosis and treatment of acromegaly: a Canadian perspective[J]. Clin Invest Med, 2000; 23(3): 172-187
27. Melmed S, Vance ML, Barkan AL, et. Current status and future opportunities for controlling acromegaly[J]. Pituitary, 2002; 5(3): 185-196
28. Barkan AL Radiotherapy in acromegaly: the argument against. Clin Endocri-nol (Oxf). 2003; 58:132-135
29. Ganz JC. Gamma knife treatment of pituitary denomas [J]. Stereotact Funct Neurosurg, 1993, 64(Suppl 1): 3-10
30．刘云廷．垂体腺瘤的研究进展[J]．北京军区医药，2000；12(4)：252-254
31. Castinetti FR, Taieb DA, Kuhn JM, et al. Outcome of Gamma Knife Radiosurgery in 82 Patient with Acromegaly: Correlation with Initial Hypersecretion[J]. J Clin Endocrinol Metabol. 2005; 90(8): 4483-4488
32. Gutt B, Wowra B, Alexandrov R, et al. Gamma-knife surgery Is Effective In Normalising Plasma Insulin-like Growth Factor-1 In Patient With Acromegaly [J]. Exp Clin Endocrinol Diabetes. 2005; 113(4): 219-224
33. Lee EJ, Anderson LM, Thimmapaya B, et al. Targeted expression of toxic fenes directed by pituitary hormone promoters: a potential atrategy for adenovirus -mediated genetherapy of pituitary tumors [J]. J Clin Endocrinol Metab,1999, 84(2): 786～794
34．范月超，张洪涛，王雄伟等．抑制pit-1基因表达对垂体生长激素腺瘤生物学行为影响的实验研究．实用医学杂志．2005；21(23)：2597-2600
35. Zhang X, Horwitz GA, Heaney AP, etal. Pituitary tumor transforming gene (PTTG)expression in pituitary adenomas [J]. J Clin Endocrinol Metab, 1999; 84(2): 761-767.
36. Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'. 2005; Eur J Endocrinol 152:379-387
37．马驰原，史继新．垂体腺瘤的基因治疗．中华神经医学杂志．2005；4(8)：855-857
38．朱涛，杨树源．肢端肥大症的药物治疗．中华神经外科杂志．2005：21(3)：188-190
39．胡吉．垂体瘤的内科治疗．国外医学内分泌分册．2005；25(4)：272-274
40．王雄伟．Pegvisomant研究现状及其在肢端肥大症中的应用．中国临床神经外科杂志．2004：9(4)：312-315
41．邵倩．垂体瘤治疗与内分泌反应．国际肿瘤学杂志．2006；33(4)：274-276
42．张正善，丁学华．垂体生长激素腺瘤的治疗进展．中国微侵袭神经外科杂志．2005；10(5)：233-235