臺灣博碩士論文加值系統

目的：
泌乳激素腺瘤(prolactinoma; PRL-oma)是腦垂體瘤(pituitary adenomas)中最常見的，所造成的病理性高泌乳激素血症(pathological hyperprolactinemia)更會導致骨質的流失，其中骨小梁的骨密度約降低20％(10％~26％)和皮質骨的骨密度約降低6％(2.5％~11％)，可是髖骨骨折的研究數據卻是很少，所以本次的研究目的是要探討腦垂體分泌腺瘤造成泌乳激素分泌異常的病患其骨質密度及髖部骨折的發生率。
材料與方法：
本次是使用橫斷面(cross sectional)的研究方式，以回溯性的方式進行樣本收集，從2009年1月之後有執行過腦下垂體磁共振檢查(pituitary gland MRI)的病患為基礎並且滿20歲以上的成年人、性別不拘，並且使用結構式問卷給予研究樣本了解其個人生理資料及危險因子，再進行髖部骨質密度(BMD)檢查以了解研究樣本的骨質疏鬆情況及T值，將相關資料利用世界衛生組織(WHO)發佈的骨折風險評估工具(FRAX®)評估病患未來骨質狀況及髖部骨折的發生率。
結果：
樣本人數共190名(平均年齡46.25歲，範圍：20~81)，其中女性佔了130名(平均年齡42.02歲，範圍：20~81歲，68.4%)，男性60名(平均年齡55.42歲，範圍：22~80歲，31.6%)，泌乳激素(PRL)異常的有93名，其中女性佔了60名而男性有33名。整個研究的樣本中雖然有停經婦女、性功能異常的男性病患及不同程度的臨床危險因子，而泌乳激素及促甲狀腺激素的分泌異常都會影響骨頭的生長與代謝，透過多項次邏輯回歸分析的結果顯示，泌乳激素腺瘤與未來骨質疏鬆及髖骨骨折的罹患率無顯著的關係，但是上述狀況與泌乳激素異常卻是有顯著的關係。
結論：
雖然泌乳激素腺瘤病患的髖部骨質密度確實比較低及較高的骨折發生率，但是上述發生的情況不再只是單一因素所引起，其中還包括年齡、月經情況、藥物治療、骨折病史、壓力狀況及其它激素的影響，都會發生骨質疏鬆。以骨質疏鬆的流行病學得知激素所引起的骨質病變已經是處於婦人停經及年齡老化之後位居第三的骨質疏鬆症疾病了，因為骨質疏鬆症及骨質疏鬆性骨折導致生活失能或死亡的機率大幅增加，相關的醫療費用與後遺症都必需付出相當大的成本與負擔，這種結果是我們必須要警覺並且做好預防保健。
關鍵字：泌乳激素腺瘤，高泌乳激素血症，骨小梁，危險因子，T值，骨折風險評估工具，髖部骨折

Abstract
Purpose：
Prolactin adenoma is the most common with a pituitary tumor, will lead to osteoporosis caused by high prolactin pathologic hyperlipidemia. In a brief of trabecular bone mineral density was reduced by approximately 20% (10% to 26%) and cortical bone mineral density was reduced by approximately 6% (2.5% ~ 11%). But the study see little of hip fracture data. So the purpose of this study is secreting pituitary adenoma to examine the causes prolactin secretion in patients with the bone density and hip fracture incidence.
Materials and Methods:
This study use of cross-sectional to research and go back to the way of the sample collection, from January 2009 after the executive pituitary magnetic resonance imaging (pituitary gland MRI) of patient full adults over 20 years of age, unisex and the use of structured questionnaire given to study biological samples to understand their personal information and risk factors. Then hip bone mineral density (BMD) examination of samples in order to assay the T-score of osteoporosis. The information using the World Health Organization (WHO) released the fracture risk assessment tool (FRAX®) assessment of bone status and future patients with hip fracture incidence.
Results:
Total number of 190 samples (mean age 46.3 years, range: 20 to 81). In which 130 women (average age 42 years, range: 20 to 81 years, 68.4%) and 60 males (mean age 55.4 years, range: 22 to 80 years, 31.6%), prolactin (PRL) abnormalities of the 93 members, including 60 women, 33 men. Although the study sample are menopausal women, sexual dysfunction in male patients and varying degrees of clinical risk factors, and prolactin and thyroid hormone secretion unusually affect bone growth and metabolism. Through the logistic regression analysis show that prolactin adenoma and osteoporosis and hip fracture prevalence no significant relationship, but have a significant positive relationship of prolactin.
Conclusion:
Although prolactin adenoma patients have lower of hip bone density and a higher incidence of fractures, but this happens including age, menstruation, medication, fracture history, pressure condition and other hormones. Epidemiology of osteoporosis, bone lesions caused by hormones is in women menopausal and aging. The substantial increase in disability living or death probability, related medical expenses and sequela cause by osteoporosis and osteoporotic fractures. This result is worth us to attention and reflection.
Keywords: Prolactin adenoma, hyperprolactinemia, trabecular bone, risk factors, T-score, fracture risk assessment tool, hip fracture

誌謝 I
中文摘要 II
英文摘要 III
目錄 IV
圖目錄 V
表目錄 VI
第一章 緒論
1.1研究背景與動機
1.2研究問題
1.3研究目的
1.4研究限制
第二章文獻探討
2.1腦垂體的功能簡介
2.2腦垂體異常所引發之疾病
2.3骨骼系統的生長及型態
2.4骨質疏鬆症的發病機制
2.5骨質減少的原因
2.6骨折風險評估
2.7 T-scores之簡介
2.8 Z-scores之簡介
2.9 FRAX®的臨床使用及危險因子簡介
第三章 研究方法與步驟
3.1 研究對象
3.2結構式問卷表
3.3器材
3.3.1磁共振檢查儀(MRI)
3.3.2放射免疫分析(RIA)
3.3.3雙能X射線骨質密度儀(DXA)
3.3.4骨折風險評估工具(FRAX®)
3.4 統計分析
第四章 結果
第五章 討論與結論
參考文獻
附件

1. Amir HH, Dina S, Robert JW. Evaluation and management of pituitary incidentalomas. Cleveland Clinic Journal of Medicine. 2008; 75(11):793-801.
2. Pituitary tumor. http://www.mayfieldclinic.com/PE-Pit.htm [Date accessed: June 1, 2011].
3. Arafah BM, Nasrallah MP. Pituitary tumors: pathophysiology, clinical manifestations and management. Endocrine-Related Cancer. 2001; 8:287-305.
4. Andrews DW. Pituitary adenomas. Current Opinion in Oncology. 1997; 9:55-60.
5. Buatti JM, Marcus RB. Pituitary adenomas: current methods of diagnosis and treatment. Oncology (Huntington). 1997; 11:791-796.
6. Ciric I, Rosenblatt S, Kerr WJ, Lamarca F, Pierce D, Baumgartner C. Perspective in pituitary adenomas: an end of the century review of tumorigenesis, diagnosis, and treatment. Clinical Neurosurgery. 2000; 47:99-111.
7. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. The Journal of Clinical Endocrinology & Metabolism. 2006; 91:4769-4775.
8. Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxford shire, UK). Endocrinol. 2010; 72(3):377-382.
9. Gary SW. Diagnosis and management of hyperprolactinemia. The Endocrinologist. 2003; 13: 52-57.
10. Prakash A, John S. Bevan. Management of pituitary tumors. The Clinician’s Practical Guide. 2nd ed. 2003; 38-58.
11. Arthur JV, James H, Sherman, Dorothy S. Luciano. Human Physiology. 7th ed. 1999.
12. Antonio C, Adrian FD, Albert B. The Epidemiology of Prolactinomas. Pituitary. 2005; 8:3-6.
13. Anne K. Prolactinomas. The New England Journal of Medicine. 2010; 362:1219-1226.
14. Gherardo M, Ernesto DM, Pier PV. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas. Pituitary. 2011; DOI 10.1007/s11102-011-0293-4.
15. Gherardo M, Ernesto DM, Tatiana M. Vertebral fractures in males with prolactinoma. Endocrine. 2011; 39(3): 288-293.
16. 蘇家聖（1987）。人體解剖與生理。台北，合記書局。中華民國七十六年十月，一版，第581-589頁。
17. Daria LT, Alberto F. Pharmacological causes of hyperprolactinemia. Therapeutics and Clinical Risk Management. 2007; 3(5): 929-951.
18. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002; 359:1761-1767.
19. Dolan P, Torgerson DJ. The cost of treating osteoporotic fractures in the United Kingdom female population. Osteoporosis International. 1998; 8:611-617.
20. Deyhim F, Mandadi K, Patil BS, Faraji B. Grapefruit pulp increases antioxidant status and improves bone quality in orchidectomized rats. Nutrition. 2008; 24(10):1039-1044.
21. Salari P, Rezaie A, Larijani B, Abdollahi M. A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Medical Science Monitor. 2008; 14(3):RA37-RA44.
22. Klibanski A, Biller BM, Rosenthal DI, Schoenfeld DA, Saxe V. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. The Journal of Clinical Endocrinology & Metabolism. 1988; 67:124-130.
23. Biller BM, Baum HB, Rosenthal DI, Saxe VC, Charpie PM, Klibanski A. Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea. The Journal of Clinical Endocrinology & Metabolism. 1992; 75:692-697.
24. Greenspan SL, Neer RM, Ridgway EC, Klibanski A. Osteoporosis in men with hyperprolactinemic hypogonadism. Annals of Internal Medicine. 1986; 104:777-782.
25. Greenspan SL, Oppenheim DS, Klibanski A. Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Annals of Internal Medicine. 1989; 110:526-531.
26. Hiroyuki O, Fumio O, Kenichi I, Jiro S, Hirofumi M. Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells. Acta Medica Okayama. 2010; 64(4):213-218.
27. Yoshihara A, Okubo Y, Tanabe A. A juvenile case of Cushing’s disease incidentally discovered with multiple bone fractures. Internal Medicine. 2007; 46(9):583-587.
28. Seriwatanachai D, Krishnamra N, Leeuwen JP. Evidence for direct effects of prolactin on human osteoblasts: inhibition of cell growth and mineralization. Journal of Cellular Biochemistry. 2009; 107(4):677-685.
29. Amal SR, Janet S. The effects of hyperprolactinemia on bone and fat. Pituitary. 2009; 12(2):96-104.
30. Schlechte JA, Sherman B, Martin R. Bone density in amenorrheic women with and without hyperprolactinemia. The Journal of Clinical Endocrinology & Metabolism. 1983; 56:1120-1123.
31. World Health Organization. Prevention and management of osteoporosis. A report of a WHO scientific group. WHO Technical Report Series 921. Geneva: WHO, 2003: 53-120.
32. Nelson BW, Bruce E, Mery S. Le B. FRAX facts. Journal of Bone and Mineral Research. 2009; 24(6): 975-979.
33. Braithwaite RS, Col NF, Wong JB. Estimating hip fracture morbidity, mortality and costs. Journal of the American Geriatrics Society. 2003; 51:364-70.
34. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observation study. Lancet. 1999; 353:878-882.
35. Kanis JA, McCloskey EV, Johansson H. Development and use of FRAX® in osteoporosis. Osteoporosis International. 2010; 21: S407-S413.
36. FRAX-WHO Facture Risk Assessment Tool. Available from http://www.shef.ac.uk/FRAX/ [Date accessed: June 1, 2011].
37. Kanis JA, McCloskey EV, Johansson H. Case finding for the management of osteoporosis with FRAX®-assessment and intervention thresholds for the UK. Osteoporosis International. 2008; 19:1395-1408.
38. John AK, Anders O, Helena J, Fredrik B, Oskar S, Eugene McCloskey. FRAX® and its applications to clinical practice. Bone. 2009; 44:734-743.
39. Nelson BW, Ethel SS. Filtering FRAX®. Osteoporosis International. 2010; 21:537-541.
40. Andrews DW. Pituitary adenomas. Current Opinion in Oncology.1997; 9:55-60.
41. Ciric I, Rosenblatt S, Kerr W, Lamarca F, Pierce D, Baumgartner C. Perspective in pituitary adenomas: an end of the century review of tumorigenesis, diagnosis, and treatment. Clinical Neurosurgery. 2000; 47:99-111.
42. Wang LG, Guo Y, Zhang X, Shi M, Song SJ, Wei LC. Analysis of the results of 143 cases of pituitary micro-adenoma treated by Linac X-Knife stereotactic radioneurosurgery. Ai Zheng. 2003; 22(5):510-513.
43. Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporosis International. 2000; 11:192-202.
44. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey EV. FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporosis International. 2008; 19:385-397.
45. Broadus AE. Mineral balance and homeostasis. In: Favus MJ. Primer on the metabolic bone diseases and disorders of mineral metabolism, 3rd ed. Philadelphia, PA, Lippincott-Raven, 1996:57–63.
46. Deyhim F, Mandadi K, Patil BS, Faraji B. Grapefruit pulp increases antioxidant status and improves bone quality in orchidectomized rats. Nutrition. 2008; 24(10):1039-1044.
47. Salari P, Rezaie A, Larijani B, Abdollahi M. A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Medical Science Monitor. 2008; 14(3):RA37- RA44.
48. 林興中(1995)骨質疏鬆症之成因。臺灣醫界。1995; 38:34-38。
49. Parfitt AM. The physiologic and pathogenetic significance of bone histomorphometric data. Disorders of Bone and Mineral Metabolism. New York, NY, Raven Press. 1992; 475-489.
50. Kanis J. Pathogenesis of osteoporosis and fracture. Osteoporosis. Oxford, Blackwell Science. 1994; 22-55.
51. Einhorn TA. The bone organ system: form and function. Osteoporosis. 1996; 3-22.
52. Fleisch H. Bone and mineral metabolism. In: Bisphosphonates in bone disease. From the laboratory to the patient, 3rd ed. New York, NY & London, the Parthenon Publishing Group. 1997; 11-31.
53. Do SH, Lee JW, Jeong WI, Chung JY, Park SJ, Hong IH, Jeon SK, Lee IS, Jeong KS. Bone-protecting effect of rubus coreanus by dual regulation of osteoblasts and osteoclasts. Menopause. 2008; 15(4Pt1):676-683.
54. Martin TJ, Udagawa N. Hormonal regulation of osteoclast function. Trends in Endocrinology & Metabolism. 1998; 9:6-12.
55. Ammann P. Transgenic mice expressing soluble tumor necrosis factor receptor are protected against bone loss caused by oestrogen deficiency. Journal of Clinical Investigation. 1997; 99:1699-1703.
56. Ducy P, Karsenty G. Genetic control of cell differentiation in the skeleton. Current Opinion in Cell Biology. 1998; 10:614-619.
57. Suda T. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrine Reviews. 1999; 20:345-357.
58. Devareddy L, Hooshmand S, Collins JK, Lucas EA, Chai SC, Arjmandi BH. Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis. The Journal of Nutritional Biochemistry. 2008; 19(10):694-699.
59. Evang JA, Carlsen SM, Svartberg J, Aanderud S, Johannesen Ø, Schreiner T, Pettersen JR , Bakke SJ, Johansen ML, Bollerslev J. Endogenous Cushing's syndrome. Tidsskr Nor Laegeforen. 2006; 126(5):599-602.
60. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. The Journal of Clinical Endocrinology & Metabolism. 2005; 90(7):4394-4398.
61. Yoshihara A, Okubo Y, Tanabe A. A juvenile case of Cushing’s disease incidentally discovered with multiple bone fractures. Internal Medicine. 2007; 46(9):583-587.
62. Public Health Service, Office of the Surgeon General. Bone health and osteoporosis: a report of the surgeon general. Washington, DC: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.
63. Bates DW, Black DM, Cummings SR. Clinical use of bone densitometry: clinical applications. The Journal of the American Medical Association. 2002; 288:1898-900.
64. Bonnick SL. Bone density in clinical practice. 2nd ed. Totowa, NJ: Humana Press. 2004; 69-91.
65. Consensus Development Conference. Diagnosis, prophylaxis and treatment of osteoporosis. The American Journal of Medicine. 1993; 94:646-650.
66. Hui SL, Slemenda CW, Johnston CC. Age and bone mass as predictors of fracture in a prospective study. The Journal of Clinical Investigation. 1988; 81:1804-1809.
67. Melton LJ III, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. Journal of Bone and Mineral Research. 1993; 8:1227-1233.
68. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. British Medical Journal. 1996; 312:1254-1259.
69. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE. Risk factors for hip fractures in white women. The New England Journal of Medicine. 1995; 332:814-815.
70. WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organization; Geneva, Switzerland. 1994. Report No.843.
71. Michael L. Fracture risk assessment in clinical practice: T-scores, FRAX, and beyond. Clinical Reviews in Bone and Mineral Metabolism. 2010; 8(3):101-112.
72. Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D. Guidelines for diagnosis and treatment of osteoporosis. Osteoporosis International. 1997; 7:390-406.
73. International Society of Clinical Densitometry (ISCD). Official positions of the International Society for Clinical Densitometry: updated 2005. Available online at www.iscd.org/visitors/positions/official.cfm.
74. John JC, Miriam FD. T-scores and Z-scores. Clinical Reviews in Bone and Mineral Metabolism. 2010; 8:113-121.
75. Dawson B, Trapp RG. Basic & clinical biostatistics. 4th ed. Hightstown, NJ: McGraw-Hill; 2004.
76. Kanis JA, Oden A, Johnell O, Johansson H, Laet DC, Brown J. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporosis International. 2007; 18:1033-1046.
77. Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. American Journal of Medicine. 2010; 123:877-884.
78. Blake GM, Fogelman I. The clinical role of dual energy X-ray absorptiometry. European Journal of Radiology. 2009; 71:406-414.
79. Washington. National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation; 2009.
80. Jameel I, Li S, Mone Z. FSH and bone 2010: evolving evidence. European Journal of Endocrinology. 2010; 163:173-176.
81. Sowers MR, Jannausch M, McConnell D, Little R, Greendale GA, Finkelstein JS, Neer RM, Johnston J, Ettinger B. Hormone predictors of bone mineral density changes during the menopausal transition. The Journal of Clinical Endocrinology and Metabolism. 2006; 91: 1261-1267.
82. Randolph JF, Sowers M, Bondarenko IV, Harlow SD, Luborsky JL, Little RJ. Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age. The Journal of Clinical Endocrinology and Metabolism. 2004; 89:1555-1561.
83. Johansson H, Kanis JA, Oden A, Johnell O, McCloskey E. BMD, clinical risk factors and their combination for hip fracture prevention. Osteoporosis International. 2009; 20:1675-1682.
84. Xu ZR, Wang AH, Wu XP, Zhang H, Sheng ZF, Wu XY, Xie H, Luo XH , Liao EY. Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women. Clinica Chimica Acta. 2009; 400:8-13.
85. Do SH, Lee JW, Jeong WI, Chung JY, Park SJ, Hong IH, Jeon SK, Lee IS, Jeong KS. Bone-protecting effect of rubus coreanus by dual regulation of osteoblasts and osteoclasts. Menopause. 2008; 15(4Pt.1):676-683.
86. Li YM, Liu SH. Estimation of the 10-year Probability of osteoporotic fracture in postmenopausal taiwanese women with FRAX. Tzu Chi Medical Journal. 2010; 22(1):29-35.
87. Prolactinomas. http://pituitaryadenomas.com/prolactinomas.htm [Date accessed: June 1, 2011].
88. Antonio C, Adrian FD, Albert B. The epidemiology of prolactinomas. Pituitary. 2005; 8:3-6.