华西医院1996～2006年1060例垂体腺瘤患者临床资料分析
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摘要
背景与目的垂体腺瘤是成人垂体前叶激素分泌功能低下或亢进的最常见原因，约占颅内肿瘤的10-15％。肿瘤占位效应、多种垂体激素分泌功能紊乱，以及术后的并发症等，可显著降低患者的生存质量，甚至威胁患者的生命。正确诊断垂体腺瘤，合理选择适当的治疗方案，对于患者健康是十分重要的。鉴于我院尚缺乏有关垂体腺瘤治疗的大宗病案报道，本研究通过分析不同类型垂体腺瘤的临床特征，旨在总结我院对此类肿瘤的治疗现状，探讨垂体腺瘤的治疗方式选择。
资料与方法从1996年至2006年8月，有1060例垂体腺瘤患者在我院诊断并治疗。按肿瘤功能性分为(1)无功能腺瘤组；(2)泌乳素瘤组；(3)生长激素瘤组；(4)促肾上腺皮质激素瘤组；(5)促甲状腺激素瘤组，总结各组在临床症状体征、影像学资料、激素水平和病理检查方面的特点。再按治疗方式分为(1)入院未治疗组；(2)单次开颅手术组；(3)单次经蝶窦手术组；(4)立体定向放射治疗组；(5)多次手术组；(6)手术结合放射治疗组，分析各组患者的特点以及治疗方式的选择。
结果男女患者各有476例和584例。微腺瘤中以泌乳素瘤最多见，占65.0％，大腺瘤和巨大腺瘤中均以无功能腺瘤为所最多，分别占61.5％和73.5％。无功能腺瘤、泌乳素瘤和生长激素瘤均以大腺瘤多见，分别占各自组的77.8％、51.5％和75.4％，促肾上腺皮质激素瘤和促甲状腺激素瘤以微腺瘤多见，前者占82.4％，后者共2例均为微腺瘤。按照临床症状体征和激素水平分类后，无功能腺瘤占53.1％为最多，其次分别为泌乳素瘤占31.3％，生长激素瘤占12.0％，促肾上腺皮质激素瘤和促甲状腺激素瘤相对少见，各占3.4％和0.2％。按照治疗方式分类后，结合肿瘤体积，微腺瘤中80.7％的患者选择立体定向放射治疗，大腺瘤中单次开颅手术者占60.7％，巨大腺瘤中仍以单次开颅手术为最多见的治疗方式，占78.0％。结合肿瘤功能性，无功能腺瘤和生长激素瘤均以单次开颅手术为最多，分别占各自组的62.7％和53.4％，而泌乳素瘤和促肾上腺皮质激素瘤则均以立体定向放射治疗为最多，分别占各自组的42.0％和57.6％。
结论手术是治疗垂体腺瘤的首选方式，我院以开颅手术更多见，经蝶窦手术开展较少。近年来在国内兴起的立体定向放射治疗在我院发展迅速，在治疗微腺瘤中逐渐成为首选方式，另外术后辅以立体定向放射治疗具有广泛前景，已逐渐替代传统放疗。
BACKGROUND&OBJECTIVE Pituitary adenomas represent 10-15%of all intracranial tumors. In adults, it is the leading cause which results inhypersecretion or hyposecretion of the anterior pituitary gland. The masseffect、the serial hormonal dysfunction, in addition to the complications ofsurgery impair the quality of life significantly, even can threaten the patients'lives. Therefore, it is important to make a proper diagnosis and choose apreferred treatment modality. Until now, the reports of large cases diagnosedas pituitary adenoma in our hospital are not available, so we design this studyto analyse the clinical features in different types of pituitary adenoma, take alook back at the treatment modalities during the past 11 years and discuss theprinciples in the choice of treatment.
MATERIALS & METHODS From 1996 January to 2006 August,1060 cases of pituitary adenomas were diagnosed and treated in West ChinaHospital. Based on the clinical symptoms and signs associated with theendocrine evaluation, we classify these cases into 5 groups in terms of tumorfunction as follows: (1)Nonfunctioning adenoma(NFA); (2)PRL-secretingadenoma; (3) GH-secreting adenoma; (4) ACTH-secreting adenoma; (5)TSH-secreting adenoma. We aim to conclude the characteristics in theaspects of symptoms and signs, CT/MRI images, hormonal tests andpathological results. Besides, we classify these cases again into 6 groups according to the treatment modality as follows: (1)no further treatment; (2)single transcranial surgery; (3) single transsphenoidal surgery; (4) stereotacticradiosurgery; (5) multiple surgeries; (6) combined treatment. For thisclassification, we analyse the patients' characteristics in different groups andthe choice of diverse treatments.
RESULTS There were 476 male patients and 584 female patients. Ofmicroadenomas, PRL-secreting adenomas accounted for 65.0%, which wasthe most common type in this group. While nonfunctioning adenomas wasthe most common type in both macroadenomas and giant macroadenomas,accounted for 61.5% and 73.5%, respectively. The tumor size innonfunctioning adenomas、PRL-secreting adenomas and GH-secretingadenomas was mostly macroadenoma, represented 77.8%、51.5% and 75.4%of the respective groups. In the other 2 groups, that is ACTH-secretingadenomas and TSH-secreting adenomas, we found microadenoma took thefirst place, accounted for 82.4% in the former, all 2 cases of the latter weremicroadenomas. There were 53.1% patients with nonfunctioning adenomas,31.3% with PRL-secreting adenomas, 12.0% with GH-secreting adenomas,3.4% with ACTH-secreting adenomas, and 0.2% with TSH-secretingadenomas. Considering the treatment modalities based on the tumor size,most patients(80.7%) with microadenomas received stereotactic radiosurgery,while single trancranial surgery was mostly adopted in treatingmacroadenomas(60.7%) and giant macroadenomas(78.0%).Single trancranialsurgery was still the most common modality in treating nonfunctioningadenomas(62.7%) and GH-secreting adenomas(53.4%), stereotacticradiosurgery was applied to treat most PRL-secreting adenomas(42.0%) andACTH-secreting adenomas(57.6%).
CONCLUSION Surgery is the preferred treatment modality. However,the transcranial route is selected rather than the transsphenoidal route in our hospital. As the development of stereotactic radiosurgery is booming indomestic hospitals, more and more patients with microadenomas would liketo receive stereotactic radiosurgery as the first choice of treatment. Inaddition, stereotactic radiosurgery as an adjuvant treatment after surgery iswidely applied and accepted, it has taken the place of the conventionalradiotherapy in the choice of post-surgery treatment.
资料与方法从1996年至2006年8月，有1060例垂体腺瘤患者在我院诊断并治疗。按肿瘤功能性分为(1)无功能腺瘤组；(2)泌乳素瘤组；(3)生长激素瘤组；(4)促肾上腺皮质激素瘤组；(5)促甲状腺激素瘤组，总结各组在临床症状体征、影像学资料、激素水平和病理检查方面的特点。再按治疗方式分为(1)入院未治疗组；(2)单次开颅手术组；(3)单次经蝶窦手术组；(4)立体定向放射治疗组；(5)多次手术组；(6)手术结合放射治疗组，分析各组患者的特点以及治疗方式的选择。
结果男女患者各有476例和584例。微腺瘤中以泌乳素瘤最多见，占65.0％，大腺瘤和巨大腺瘤中均以无功能腺瘤为所最多，分别占61.5％和73.5％。无功能腺瘤、泌乳素瘤和生长激素瘤均以大腺瘤多见，分别占各自组的77.8％、51.5％和75.4％，促肾上腺皮质激素瘤和促甲状腺激素瘤以微腺瘤多见，前者占82.4％，后者共2例均为微腺瘤。按照临床症状体征和激素水平分类后，无功能腺瘤占53.1％为最多，其次分别为泌乳素瘤占31.3％，生长激素瘤占12.0％，促肾上腺皮质激素瘤和促甲状腺激素瘤相对少见，各占3.4％和0.2％。按照治疗方式分类后，结合肿瘤体积，微腺瘤中80.7％的患者选择立体定向放射治疗，大腺瘤中单次开颅手术者占60.7％，巨大腺瘤中仍以单次开颅手术为最多见的治疗方式，占78.0％。结合肿瘤功能性，无功能腺瘤和生长激素瘤均以单次开颅手术为最多，分别占各自组的62.7％和53.4％，而泌乳素瘤和促肾上腺皮质激素瘤则均以立体定向放射治疗为最多，分别占各自组的42.0％和57.6％。
结论手术是治疗垂体腺瘤的首选方式，我院以开颅手术更多见，经蝶窦手术开展较少。近年来在国内兴起的立体定向放射治疗在我院发展迅速，在治疗微腺瘤中逐渐成为首选方式，另外术后辅以立体定向放射治疗具有广泛前景，已逐渐替代传统放疗。
BACKGROUND&OBJECTIVE Pituitary adenomas represent 10-15%of all intracranial tumors. In adults, it is the leading cause which results inhypersecretion or hyposecretion of the anterior pituitary gland. The masseffect、the serial hormonal dysfunction, in addition to the complications ofsurgery impair the quality of life significantly, even can threaten the patients'lives. Therefore, it is important to make a proper diagnosis and choose apreferred treatment modality. Until now, the reports of large cases diagnosedas pituitary adenoma in our hospital are not available, so we design this studyto analyse the clinical features in different types of pituitary adenoma, take alook back at the treatment modalities during the past 11 years and discuss theprinciples in the choice of treatment.
MATERIALS & METHODS From 1996 January to 2006 August,1060 cases of pituitary adenomas were diagnosed and treated in West ChinaHospital. Based on the clinical symptoms and signs associated with theendocrine evaluation, we classify these cases into 5 groups in terms of tumorfunction as follows: (1)Nonfunctioning adenoma(NFA); (2)PRL-secretingadenoma; (3) GH-secreting adenoma; (4) ACTH-secreting adenoma; (5)TSH-secreting adenoma. We aim to conclude the characteristics in theaspects of symptoms and signs, CT/MRI images, hormonal tests andpathological results. Besides, we classify these cases again into 6 groups according to the treatment modality as follows: (1)no further treatment; (2)single transcranial surgery; (3) single transsphenoidal surgery; (4) stereotacticradiosurgery; (5) multiple surgeries; (6) combined treatment. For thisclassification, we analyse the patients' characteristics in different groups andthe choice of diverse treatments.
RESULTS There were 476 male patients and 584 female patients. Ofmicroadenomas, PRL-secreting adenomas accounted for 65.0%, which wasthe most common type in this group. While nonfunctioning adenomas wasthe most common type in both macroadenomas and giant macroadenomas,accounted for 61.5% and 73.5%, respectively. The tumor size innonfunctioning adenomas、PRL-secreting adenomas and GH-secretingadenomas was mostly macroadenoma, represented 77.8%、51.5% and 75.4%of the respective groups. In the other 2 groups, that is ACTH-secretingadenomas and TSH-secreting adenomas, we found microadenoma took thefirst place, accounted for 82.4% in the former, all 2 cases of the latter weremicroadenomas. There were 53.1% patients with nonfunctioning adenomas,31.3% with PRL-secreting adenomas, 12.0% with GH-secreting adenomas,3.4% with ACTH-secreting adenomas, and 0.2% with TSH-secretingadenomas. Considering the treatment modalities based on the tumor size,most patients(80.7%) with microadenomas received stereotactic radiosurgery,while single trancranial surgery was mostly adopted in treatingmacroadenomas(60.7%) and giant macroadenomas(78.0%).Single trancranialsurgery was still the most common modality in treating nonfunctioningadenomas(62.7%) and GH-secreting adenomas(53.4%), stereotacticradiosurgery was applied to treat most PRL-secreting adenomas(42.0%) andACTH-secreting adenomas(57.6%).
CONCLUSION Surgery is the preferred treatment modality. However,the transcranial route is selected rather than the transsphenoidal route in our hospital. As the development of stereotactic radiosurgery is booming indomestic hospitals, more and more patients with microadenomas would liketo receive stereotactic radiosurgery as the first choice of treatment. Inaddition, stereotactic radiosurgery as an adjuvant treatment after surgery iswidely applied and accepted, it has taken the place of the conventionalradiotherapy in the choice of post-surgery treatment.
引文
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28. Lancranjan I, Bruns C, Grass P, et al. Sandostatin LAR ((TM)): Pharmacokinetics, pharmacodynamics.efficacy, and tolerability in acromegalic patients. Metabolism: Clinical & Experimental. 1995,44(Suppl 1): 18-26
29. Amato G, Mazziotti G, Rotondi M, et al. Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly. Clinical endocrinology. 2002 Jan, 56(1): 65-71
30. Chanson P, Boerlin V, Ajzenberg C, et al. Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly. Clinical endocrinology. 2000 Nov, 53(5): 577-86
31. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. The New England journal of medicine.2000 Apr 342(16): 1171 -7
32. Herman-Bonert VS, Zib K, Scarlett JA, et al. Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. The Journal of clinical endocrinology and metabolism, 2000 Aug 85(8): 2958-61
33. Barkan AL, Burman P, Clemmons DR, et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005 Oct, 90(10): 5684-91
34. Kobayashi T, Mori Y, Uchiyama Y, et al. Long-term results of gamma knife surgery for growth hormone-producing pituitary adenoma: is the disease difficult to cure? J-Neurosurg. 2005,102 (Suppl): 119-23
35. Wang MH, Liu P, Liu AL, et al. Efficacy of gamma knife radiosurgery in treatment of growth hormone-secreting pituitary adenoma. Zhonghua-Yi-Xue-Za-Zhi.2003 Dec 10,83(23): 2045-8
36. Attanasio R, Epaminonda P, Motti E, et al. Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J-Clin-Endocrinol-Metab. 2003 Jul, 88(7): 3105-12
37. Zhang N, Pan L, Wang EM, et al. Radiosurgery for growth hormone-producing pituitary adenomas. J-Neurosurg. 2000 Dec, 93(Suppl 3): 6-9
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39. Kasperlik-Zaluska A, Migdalska B, Jeske W, et al. The effect of magnesium valproate on plasma ACTH concentrations in Nelson's syndrome. Acta medica Polona, 1989,30(1-2):9-15
40. Ambrosi B, Bochicchio D, Fadin C, et al.Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-adrenal function in patients with corticotropin hypersecretion.Journal of Endocrinological Investigation , 1990,13(3):257-261
41. Mercado-Asis LB, Yanovski JA, Tracer HL, et al. Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome. The Journal of clinical endocrinology and metabolism, 1997 Feb, 82(2):514-7
42. Thoren M, Adamson U, Sjoberg HE.Aminoglutethimide and metyrapone in the management of Cushing's syndrome.Acta endocrinologica,1985 Aug 109(4):451-7
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44. Engelhardt D, Jacob K, Doerr HG Different therapeutic efficacy of ketoconazole in patients with Cushing's syndrome. Klinische Wochenschrift, 1989 Feb, 67 (4): 241-7
45. Bertagna X, Bertagna C, Laudat MH, et al.Pituitary-adrenal response to the antiglucocorticoid action of RU 486 in Cushing's syndrome.The Journal of clinical endocrinology and metabolism, 1986 Sep 63(3):639-43
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30. Chanson P, Boerlin V, Ajzenberg C, et al. Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly. Clinical endocrinology. 2000 Nov, 53(5): 577-86
31. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. The New England journal of medicine.2000 Apr 342(16): 1171 -7
32. Herman-Bonert VS, Zib K, Scarlett JA, et al. Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. The Journal of clinical endocrinology and metabolism, 2000 Aug 85(8): 2958-61
33. Barkan AL, Burman P, Clemmons DR, et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005 Oct, 90(10): 5684-91
34. Kobayashi T, Mori Y, Uchiyama Y, et al. Long-term results of gamma knife surgery for growth hormone-producing pituitary adenoma: is the disease difficult to cure? J-Neurosurg. 2005,102 (Suppl): 119-23
35. Wang MH, Liu P, Liu AL, et al. Efficacy of gamma knife radiosurgery in treatment of growth hormone-secreting pituitary adenoma. Zhonghua-Yi-Xue-Za-Zhi.2003 Dec 10,83(23): 2045-8
36. Attanasio R, Epaminonda P, Motti E, et al. Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J-Clin-Endocrinol-Metab. 2003 Jul, 88(7): 3105-12
37. Zhang N, Pan L, Wang EM, et al. Radiosurgery for growth hormone-producing pituitary adenomas. J-Neurosurg. 2000 Dec, 93(Suppl 3): 6-9
38. Reincke M, Allolio B, Kaulen D,et al. The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease. Klinische Wochenschrift, 1988 Aug,66(15):686-9
39. Kasperlik-Zaluska A, Migdalska B, Jeske W, et al. The effect of magnesium valproate on plasma ACTH concentrations in Nelson's syndrome. Acta medica Polona, 1989,30(1-2):9-15
40. Ambrosi B, Bochicchio D, Fadin C, et al.Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-adrenal function in patients with corticotropin hypersecretion.Journal of Endocrinological Investigation , 1990,13(3):257-261
41. Mercado-Asis LB, Yanovski JA, Tracer HL, et al. Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome. The Journal of clinical endocrinology and metabolism, 1997 Feb, 82(2):514-7
42. Thoren M, Adamson U, Sjoberg HE.Aminoglutethimide and metyrapone in the management of Cushing's syndrome.Acta endocrinologica,1985 Aug 109(4):451-7
43. Kasperlik-Zaluska AA, Migdalska B, Jeske W, et al.Effect of aminoglutethimide on ACTH plasma levels in Cushing's disease and Nelson syndrome.Polski tygodnik lekarski, 1992,47(44-45): 1006-8
44. Engelhardt D, Jacob K, Doerr HG Different therapeutic efficacy of ketoconazole in patients with Cushing's syndrome. Klinische Wochenschrift, 1989 Feb, 67 (4): 241-7
45. Bertagna X, Bertagna C, Laudat MH, et al.Pituitary-adrenal response to the antiglucocorticoid action of RU 486 in Cushing's syndrome.The Journal of clinical endocrinology and metabolism, 1986 Sep 63(3):639-43