臺灣博碩士論文加值系統

背景：原發性皮質酫酮症為次發性高血壓中最常見的原因，通常是因單側腎上腺腺瘤或是雙側腎上腺增生引起，前者手術治療可治癒，後者則以內科治療為主。斷層掃描、腎上腺靜脈血取樣與核子醫學腎上腺掃描常被用來評估原發性皮質酫酮症之病因以及患側診斷，腹部斷層掃描可評估腎上腺病灶之解剖學特徵，但其敏感度差異很大；腎上腺靜脈血取樣為現今之診斷標準，但為侵入性檢查，且具高度技術需求；核子醫學腎上腺掃描早期受限於影像解析度不足，效果不彰，隨著單光子放射斷層攝影術與斷層掃描融合技術的發展，準確度大幅提升。以上檢查之準確度及適用時機未有定論，但至今未有研究對其成本及效果進行分析。

目的：本研究探討腹部斷層掃描（CT）、核子醫學腎上腺掃描平面造影（NP-59 planar）、輔以單光子放射斷層攝影術（NP-59 SPECT）以及輔以單光子放射斷層攝影術併斷層掃描融合技術（NP-59 SPECT/CT）四種影像學檢查，在診斷原發性皮質酫酮症病因上之準確性、平均醫療成本以及成本效果分析。

方法：本研究回溯式搜尋TAIPAI資料庫，共27位原發性皮質酫酮症病患納入研究，皆有接受腹部斷層掃描與核子醫學腎上腺掃描，並以最終病理結果為診斷標準。研究中分析四項檢查之準確度，並以決策樹模型之方式，計算機率與平均成本，設定檢查準確度與檢查效用度為效果指標，探討成本效果分析，最後以敏感度分析方式探討變項變化對平均成本之影響。

結果：四種檢查中，NP-59 SPECT/CT準確度最高，與CT及NP-59 planar相比，呈現邊緣性的統計意義。平均成本亦以NP-59 SPECT/CT最低，NP-59 planar為平均成本最高之檢查。以檢查準確度為效果指標時，NP-59 SPECT/CT之成本效果比值最低；以檢查應用度為效果指標時，NP-59 SPECT/CT之成本效果比值亦為最低，NP-59 planar則為無效之檢查。敏感度分析中以NP-59 SPECT/CT之敏感度為變相變化時，即使其敏感度降至0%，平均成本亦低於CT；以NP-59 SPECT/CT之特異度為變相變化時，當其特異度降至59.5%以下時，NP-59 SPECT/CT之平均成本開始高於CT之平均成本。

結論：本研究顯示NP-59 SPECT/CT在診斷原發性皮質酫酮症之病因上述四種影像學檢查中最為準確，平均成本最低，成本效果比值最低之檢查。NP-59 SPECT/CT在敏感度與特異度的變動上保有對於CT之成本效果比值優勢。依此結論可提供臨床醫師在處理原發性皮質酫酮症時另一種參考方向，採用更有效果之處置。

Background：Primary aldosteronism is the most common cause of secondary hypertension. The two main causes of primary aldosteronism are aldosterone-producing adenoma, which could be cured by surgical intervention, and bilateral adrenal hyperplasia, which should be medical-treated. Computed tomography, adrenal venous sampling and adrenal scintigraphy are usually used for the etiology and lateralization of primary aldosteronism. Computed tomography is based on the anatomical findings, but it has wide variation of sensitivity. Adenal venous sampling is the gold standard for latearalization, but it is invasive and highly technical-dependent. Adrenal scintigraphy has limited role in primary aldosteronism during early days due to resolution. With the SPECT and SPECT/CT fusion imaging techique, the accuracy of adrenal scintigraphy is significant improved. The clinical algorithm for these modalities has not been well-established, and there are no studies concerning about the cost-effectiveness.

Objective：This study aimed on the comparison of the accuracy, average cost and cost-effectiveness analysis of four imaging modalities for differentiating the etiology of primary aldosteronism, including CT, NP-59 planar, NP-59 SPECT and NP-59 SPECT/CT.

Methods：We retrospectively included 27 clinical-confirmed primary aldosteronism patients from TAIPAI database. All of them had CT, NP-59 adrenal scintigraphy (plaran, SPECT and SPECT/CT) studies and pathology reports of adrenal lesion. The accuracy and average cost of these four imaging modalities were analyzed. By decision tress and setting effectiveness as diagnostic accuracy and diagnostic utility, cost-effectiveness were also analyzed. Sensitivity analysis were performed to determine the impact on the average cost while the variables changed.

Results：NP-59 SPECT/CT is the most accurate study among four imaging modalities, with borderline significance as compared with NP-59 planar and CT. NP-59 SPECT/CT bares the lowest average cost, and NP-59 planar bares the highest average cost. By setting diagnostic accuracy as the effectiveness, NP-59 SPECT/CT has the lowest cost-effectiveness ratio. If setting diagnostic utility as the effectiveness, NP-59 planar is considered a ineffectiveness study. In sensitivity analysis, if the sensitivity of NP-59 SPECT/CT decreases to 0%, the average cost of NP-59 SPECT/CT is still lower the average cost of CT. The average cost of NP-59 SPECT/CT is higher than the average cost of CT while the specificity of NP-59 SPECT/CT decreases to 59.5%.

Conclusion：Our study suggests that NP-59 SPECT/CT is the most accurate, the lowest average cost and the most cost-effective study among these four imaging modalities in differentiating the etiology of primary aldosteronism. It shows no significant impact on cost-effectiveness ratio as compared with CT while the sensitivity and specificity of NP-59 SPECT/CT changes. Aside from clinical concern, this result provides physicians consider the decision in another way to provide more effective management in primary aldosteronism.

中文摘要 I
Abstract III
表目錄 VII
圖目錄 VIII
第一章 緒論 1
第一節 研究背景 1
第二節 研究目的 3
第二章 文獻探討 4
第一節 原發性皮質酫酮症 4
第二節 腹部電腦斷層掃描與腹部核磁共振掃描 6
第三節 腎上腺靜脈血液採樣 7
第四節 核子醫學腎上腺掃描 9
第五節 單光子放射斷層攝影與斷層掃描融合技術 10
第六節 成本效果分析 12
一、成本 12
二、效果 12
三、分析 13
四、效果的選擇 14
第三章 材料與方法 16
第一節 研究樣本 16
第二節 研究方法與架構 16
一、研究假設 16
二、腹部斷層掃描與核子醫學腎上腺掃描之檢查與結果判讀 17
三、決策樹 18
（一）決策樹模型 18
（二）機率 19
（三）成本計算 19
四、成本效果分析 21
（一）效果指標 22
（二）評估指標 22
四、敏感度分析 22
第三節 資料處理與分析 23
一、資料處理 23
二、資料分析 23
第四章 研究結果 24
第一節 檢查準確度 24
第二節 各項影像學檢查平均成本 25
第三節 成本效果分析 25
第四節 敏感度分析 25
第五章 討論 27
參考文獻 34

1.Rossi, G.P., T.M. Seccia, and A.C. Pessina, Primary aldosteronism: part II: subtype differentiation and treatment. J Nephrol, 2008. 21(4): p. 455-62.
2.Patel, S.M., et al., Role of radiology in the management of primary aldosteronism. Radiographics, 2007. 27(4): p. 1145-57.
3.Tsushima, Y., H. Ishizaka, and M. Matsumoto, Adrenal masses: differentiation with chemical shift, fast low-angle shot MR imaging. Radiology, 1993. 186(3): p. 705-9.
4.Magill, S.B., et al., Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism. J Clin Endocrinol Metab, 2001. 86(3): p. 1066-71.
5.Scoggins, B.A., et al., Preoperative lateralisation of aldosterone-producing tumours in primary aldosteronism. Ann Intern Med, 1972. 76(6): p. 891-7.
6.Conn, J.W., et al., Normokalemic Primary Aldosteronism. A Detectable Cause of Curable "Essential" Hypertension. JAMA, 1965. 193: p. 200-6.
7.Conn, J.W., The evolution of primary aldosteronism: 1954-1967. Harvey Lect, 1966. 62: p. 257-91.
8.Gordon, R.D., et al., Evidence that primary aldosteronism may not be uncommon: 12% incidence among antihypertensive drug trial volunteers. Clin Exp Pharmacol Physiol, 1993. 20(5): p. 296-8.
9.Young, W.F., Jr., et al., Primary aldosteronism: diagnosis and treatment. Mayo Clin Proc, 1990. 65(1): p. 96-110.
10.Conn, J.W., A concluding response. Arch Intern Med, 1969. 123(2): p. 154-5.
11.Kaplan, N.M., The current epidemic of primary aldosteronism: causes and consequences. J Hypertens, 2004. 22(5): p. 863-9.
12.Rossi, G.P., et al., A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol, 2006. 48(11): p. 2293-300.
13.Rossi, G.P., T.M. Seccia, and A.C. Pessina, Primary aldosteronism - part I: prevalence, screening, and selection of cases for adrenal vein sampling. J Nephrol, 2008. 21(4): p. 447-54.
14.Dunn, P.J. and E.A. Espiner, Outpatient screening tests for primary aldosteronism. Aust N Z J Med, 1976. 6(2): p. 131-5.
15.Mulatero, P., et al., Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab, 2008. 93(4): p. 1366-71.
16.Young, W.F., et al., Role for adrenal venous sampling in primary aldosteronism. Surgery, 2004. 136(6): p. 1227-35.
17.Kloos, R.T., et al., Incidentally discovered adrenal masses. Endocr Rev, 1995. 16(4): p. 460-84.
18.Funder, J.W., et al., Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2008. 93(9): p. 3266-81.
19.Rossi, G.P., et al., Imaging of aldosterone-secreting adenomas: a prospective comparison of computed tomography and magnetic resonance imaging in 27 patients with suspected primary aldosteronism. J Hum Hypertens, 1993. 7(4): p. 357-63.
20.Geisinger, M.A., et al., Primary hyperaldosteronism: comparison of CT, adrenal venography, and venous sampling. AJR Am J Roentgenol, 1983. 141(2): p. 299-302.
21.Ishibashi, T., et al., Primary aldosteronism: a pictorial essay. Abdom Imaging, 2007. 32(4): p. 504-14.
22.Vonend, O., et al., [Comparison of adrenal imaging and selective adrenal vein sampling in primary hyperaldosteronism]. Dtsch Med Wochenschr, 2007. 132(46): p. 2436-41.
23.Harris, D.A., et al., Review of surgical management of aldosterone secreting tumours of the adrenal cortex. Eur J Surg Oncol, 2003. 29(5): p. 467-74.
24.Ikeda, D.M., et al., The detection of adrenal tumors and hyperplasia in patients with primary aldosteronism: comparison of scintigraphy, CT, and MR imaging. AJR Am J Roentgenol, 1989. 153(2): p. 301-6.
25.Lumachi, F., et al., Non-invasive adrenal imaging in primary aldosteronism. Sensitivity and positive predictive value of radiocholesterol scintigraphy, CT scan and MRI. Nucl Med Commun, 2003. 24(6): p. 683-8.
26.Lingam, R.K., et al., Diagnostic performance of CT versus MR in detecting aldosterone-producing adenoma in primary hyperaldosteronism (Conn''s syndrome). Eur Radiol, 2004. 14(10): p. 1787-92.
27.Namimoto, T., et al., Adrenal masses: quantification of fat content with double-echo chemical shift in-phase and opposed-phase FLASH MR images for differentiation of adrenal adenomas. Radiology, 2001. 218(3): p. 642-6.
28.Melby, J.C., et al., Diagnosis and localization of aldosterone-producing adenomas by adrenal-vein cateterization. N Engl J Med, 1967. 277(20): p. 1050-6.
29.Satoh, F., et al., Localization of aldosterone-producing adrenocortical adenomas: significance of adrenal venous sampling. Hypertens Res, 2007. 30(11): p. 1083-95.
30.Minami, I., et al., Diagnostic accuracy of adrenal venous sampling in comparison with other parameters in primary aldosteronism. Endocr J, 2008. 55(5): p. 839-46.
31.Young, W.F., Jr., Minireview: primary aldosteronism--changing concepts in diagnosis and treatment. Endocrinology, 2003. 144(6): p. 2208-13.
32.Daunt, N., Adrenal vein sampling: how to make it quick, easy, and successful. Radiographics, 2005. 25 Suppl 1: p. S143-58.
33.NA, W., Practical interventional uroradiology. Edinburg, scoland: Edward Arnold, 1993. chap 11.
34.jj, B., The roles of angiography in adrenal disease. Abram''s angiography, 1983. 3rd ed. Boston, Mass: Little, Brown.
35.Rossi, G.P., et al., Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases. J Clin Endocrinol Metab, 2001. 86(3): p. 1083-90.
36.Counsell, R.E., et al., Tumor localizing agents. IX. Radioiodinated cholesterol. Steroids, 1970. 16(3): p. 317-28.
37.Sarkar, S.D., et al., A new and superior adrenal scanning agent, NP-59. J Nucl Med, 1975. 16(11): p. 1038-42.
38.Sarkar, S.D., et al., A new and superior adrenal imaging agent, 131I-6beta-iodomethyl-19-nor-cholesterol (NP-59): evaluation in humans. J Clin Endocrinol Metab, 1977. 45(2): p. 353-62.
39.Gross, M.D., et al., The normal dexamethasone-suppression adrenal scintiscan. J Nucl Med, 1979. 20(11): p. 1131-5.
40.Gross, M.D., et al., The role of parmacologic manipulation in adrenal cortical scintigraphy. Semin Nucl Med, 1981. 11(2): p. 128-48.
41.Hwang, I., et al., Adrenocortical SPECT using iodine-131 NP-59. J Nucl Med, 1998. 39(8): p. 1460-3.
42.Perault, C., et al., Thoracic and abdominal SPECT-CT image fusion without external markers in endocrine carcinomas. The Group of Thyroid Tumoral Pathology of Champagne-Ardenne. J Nucl Med, 1997. 38(8): p. 1234-42.
43.Frank, A., et al., Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings. Int J Radiat Oncol Biol Phys, 1995. 32(5): p. 1495-512.
44.Czernin, J., M. Allen-Auerbach, and H.R. Schelbert, Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med, 2007. 48 Suppl 1: p. 78S-88S.
45.von Schulthess, G.K., H.C. Steinert, and T.F. Hany, Integrated PET/CT: current applications and future directions. Radiology, 2006. 238(2): p. 405-22.
46.Avram, A.M., L.M. Fig, and M.D. Gross, Adrenal gland scintigraphy. Semin Nucl Med, 2006. 36(3): p. 212-27.
47.Gross, M.D., et al., Contemporary adrenal scintigraphy. Eur J Nucl Med Mol Imaging, 2007. 34(4): p. 547-57.
48.Hogan, M.J., et al., Location of aldosterone-producing adenomas with 131I-19-iodocholesterol. N Engl J Med, 1976. 294(8): p. 410-4.
49.Nomura, K., et al., Iodomethylnorcholesterol uptake in an aldosteronoma shown by dexamethasone-suppression scintigraphy: relationship to adenoma size and functional activity. J Clin Endocrinol Metab, 1990. 71(4): p. 825-30.
50.Mansoor, G.A., et al., Unilateral adrenal hyperplasia causing primary aldosteronism: limitations of I-131 norcholesterol scanning. Am J Hypertens, 2002. 15(5): p. 459-64.
51.Weinberger, M.H., et al., Primary aldosteronism: diagnosis, localization, and treatment. Ann Intern Med, 1979. 90(3): p. 386-95.
52.Gordon, R.D., Primary aldosteronism. J Endocrinol Invest, 1995. 18(7): p. 495-511.
53.Vetter, H., et al., Primary aldosteronism: diagnosis and noninvasive lateralization procedures. Cardiology, 1985. 72 Suppl 1: p. 57-63.
54.Gross, M.D., B. Shapiro, and J.E. Freitas, Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy. J Nucl Med, 1985. 26(1): p. 43-8.
55.Buck, A.K., et al., Spect/Ct. J Nucl Med, 2008. 49(8): p. 1305-19.
56.Yen, R.F., et al., 131I-6beta-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results. J Nucl Med, 2009. 50(10): p. 1631-7.
57.Yen, R.F., et al., The cost-utility analysis of 18-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of recurrent nasopharyngeal carcinoma. Acad Radiol, 2009. 16(1): p. 54-60.
58.Schreyogg, J., et al., Cost-effectiveness of hybrid PET/CT for staging of non-small cell lung cancer. J Nucl Med, 2010. 51(11): p. 1668-75.
59.Min, J.K., et al., Cost-effectiveness of coronary CT angiography versus myocardial perfusion SPECT for evaluation of patients with chest pain and no known coronary artery disease. Radiology, 2010. 254(3): p. 801-8.
60.Bjorge, T., et al., BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case-control study. Br J Cancer, 2004. 91(10): p. 1829-34.
61.Brozek, I., et al., High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland. Gynecol Oncol, 2008. 108(2): p. 433-7.
62.Antoniou, A., et al., Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet, 2003. 72(5): p. 1117-30.
63.Brose, M.S., et al., Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst, 2002. 94(18): p. 1365-72.
64.Chen, S., et al., Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol, 2006. 24(6): p. 863-71.
65.Ford, D., et al., Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet, 1998. 62(3): p. 676-89.
66.Kwon, J.S., et al., Preventing future cancers by testing women with ovarian cancer for BRCA mutations. J Clin Oncol, 2010. 28(4): p. 675-82.
67.Patton, D.D. and J.M. Woolfenden, A utility-based model for comparing the cost-effectiveness of diagnostic studies. Invest Radiol, 1989. 24(4): p. 263-71.
68.Dwamena, B.A., et al., Diagnostic evaluation of the adrenal incidentaloma: decision and cost-effectiveness analyses. J Nucl Med, 1998. 39(4): p. 707-12.
69.Rossi, G., et al., Prevalence of extracranial carotid artery lesions at duplex in primary aldosteronism. Am J Hypertens, 1993. 6(1): p. 8-14.
70.Conn, J.W., R.F. Knopf, and R.M. Nesbit, Clinical Characteristics of Primary Aldosteronism from an Analysis of 145 Cases. Am J Surg, 1964. 107: p. 159-72.
71.Yamahara, K., et al., New diagnostic procedure for primary aldosteronism: adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker--application to a case of bilateral multiple adrenal microadenomas. Hypertens Res, 2002. 25(2): p. 145-52.
72.Lins, P.E. and U. Adamson, Primary aldosteronism. A follow-up study of 28 cases of surgically treated aldosterone-producing adenomas. Acta Med Scand, 1987. 221(3): p. 275-82.
73.Wu, V.C., et al., Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia. QJM, 2008. 101(1): p. 13-22.
74.Novitsky, Y.W., et al., Clinical outcomes of laparoscopic adrenalectomy for lateralizing nodular hyperplasia. Surgery, 2005. 138(6): p. 1009-16; discussion 1016-7.
75.Goitein, D., et al., Laparoscopic adrenalectomy: ascending the learning curve. Surg Endosc, 2004. 18(5): p. 771-3.
76.Assalia, A. and M. Gagner, Laparoscopic adrenalectomy. Br J Surg, 2004. 91(10): p. 1259-74.
77.Bergamini, C., et al., Complications in laparoscopic adrenalectomy: the value of experience. Surg Endosc, 2011.