Case Discussion < Presentation of Case > 　　A 20-year-old woman was referred to our clinic due to newly diagnosed hypertension with hypokalemia. The patient had been in her usual state of health until 3 months earlier, when she developed malaise and bilateral leg weakness. Her blood pressure was 170/110 mmHg on physical examination. There was no moon face, buffalo hump, central obesity, purple striae, edema, abdominal mass, or bruits. Under the impression of secondary hypertension, serial investigations were performed, which are shown in Table. Laboratory findings revealed hypokalemia (3.0 mEq/L), elevated plasma renin activity (PRA), and increased plasma aldosterone concentration (PAC). Angiography showed patent renal arteries. Magnetic resonance imaging of the abdomen revealed a left renal tumor that had hyperintense signal on T2-weighted image and contrast enhancement in T1 (Figure 1). Bilateral renal venous sampling showed a renin lateralization ratio of 1.76 (left/right). Treatments for her hypertension with 3 categories of agents (alpha blocker, angiotensin receptor blocker and spironolactone) were ineffective to control her hypertension, and she developed nausea and intermittent vomiting with worsening blood pressure control. Further computed tomography-guided biopsy showed renal cortical tumor composed of uniform polygonal cells with occasional peri-nuclear halo, arranged in hemangiopericytic patterns in pathology (Figure 2). The cells were all immunohistochemically positive for actin and negative for cytokeratin and HMB-45, which was compatible with juxtaglomerular cell tumor. She underwent radiofrequency ablation of the renal tumor. Her systolic blood pressure decreased to 100~110 mmHg on the same day without any medical control. Follow-up laboratory examinaitons showed normalization of PRA and serum potassium levels. < Laboratory data > 1.Results of baseline data BUN CRE Na K ALB AST ALT CK mg/dL mg/dL mmol/L mmol/L g/dL U/L U/L U/L 11.4 1.3 137 3.0 3.8 37 32 112 2.Results of the baseline endocrinologic tests PRA (ng/ml/hr) PAC (ng/dL) 1-5 ng/ml/hr 5-30ng/dL 38.3 96.4 ***PRA= plasma rennin activity ***PAC= plasma aldosterone concentration 3.Results of PAC and PRA in sampling of the renal veins   Left Right IVC Plasma Renal vein Adrenal vein Renal vein Adrenal vein PAC (ng/dL) 101.2 505.6 143.4 355 191.6 39.4 PRA (ng/ml/hr) 20.14 7.64 11.41 30.84 9.81 8.56 *** IVC = inferior vena cava < 病例解析 > 腎素瘤( reninoma)是源自腎絲球傍細胞的腫瘤(juxtaglomerular cell tumor)，會過度分泌腎素(renin)，造成血中皮質醛酮濃度(plasma aldosterone concentration, PAC)升高而進一步引起低血鉀及高血壓，是一種可治癒的高血壓疾病。若不及早治療，長期的高血壓會造成器官的損壞；據文獻統計，視網膜病變就達到24%左右，蛋白尿、腎功能不全及左心室肥大則各佔11.3%及7%之多。至於腦中風及腸缺血則較少發生。此病好發在年輕女性。常見的症狀包括年輕型的高血壓及其他頭痛、夜尿、多喝、多尿、倦怠等非專一性的表現。一般在門診檢查針對年輕發病的高血壓併低血鉀，若不如預期 (正常身體因應高血壓時血中皮質醛酮素會降低)，皮質醛酮素不降反升，則需要考慮到原發性高皮質醛酮素症( primary aldosteronism )、腎動脈狹窄及腎素瘤的可能性。若血液檢查同時有高腎素 (renin)的表現，則排除掉原發性高皮質醛酮素症，進一步會安排影像學檢查，血管攝影可以排除是否有腎動脈狹窄的可能性。而腹部電腦斷層或磁振攝影可以用來偵測腎臟皮質的病灶，即腎素瘤。最後確診則須作侵入性的腎靜脈抽樣 (renal vein sampling )確定有腫瘤分泌腎素 (renin)。治療以手術去除腫瘤為主，若手術風險大的病人可用放射電燒灼術(radiofrequency ablation)來替代，大部分病人術後高血壓都能有明顯下降或恢復正常。 < 參考文獻 > Wong L, et al. Case report and literature review. J Hypertens. 2008 Feb;26(2):368-73. Gottardo F, et al. A kidney tumor in an adolescent with severe hypertension and hypokalemia: an uncommon case--case report and review of the literature on reninoma. Urol Int. 2010 Jul;85(1):121-4 繼續教育考題 1. (D) Which statement is incorrect about reninoma? A Reninoma is a tumor of the renal juxtaglomerular cell apparatus B It causes hypertension and hypokalemia because of hypersecretion of renin C Following partial nephrectomy, the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) decline rapidly and the blood pressure normalizes. D The blood pressure could be controlled after treatment with ACEI (Angiotensin-converting Enzyme Inhibitors) and calcium channel blockers 2. (B) Which of the following description is not the presentation of reninoma? A Elevation of PRA and PAC B Associated with hypertension and hyperkalemia. C Common symptoms include headache, nocturia, polyuria, polydipsia, and fatigue. D Reninoma is a surgically correctable cause of hypertension. 3. (D) Which of the following situations for hypertension should prompt a search for secondary hypertension? A Age younger than 30 years when hypertension is detected B Hypertension that is difficult to control by medical therapy C Association with hypokalemia or metabolic alkalosis D All of the above. 4. (C) Which of the following diseases is associated with presentation of low PRA? A Reninoma B Atherosclerotic renal artery stenosis C Primary aldosteronism D Renal artery hyperplasia 5. (D) Which of the following diseases is not associated with hypokalemia at presentation? A Reninoma B Primary aldosteronism C Gitelman's syndrome D Pseudohypoaldosteronisms 6. (B) What is the most approprriate management for reninoma? A Chemotherapy B Surgical intervention C Rehabilization D  Pharmacotherapy 答案解說 ( D ) 腎素瘤無法以藥物完全治療控制住血壓，大部分需要開刀切除腫瘤才能根治。 ( B ) 腎素瘤會造成次發性皮質醛酮升高，而進一步引起高血壓及低血鉀。 ( D ) 以上皆是。 ( C ) 原發性皮質醛酮症的血中腎素濃度是低的，且血中皮質醛酮濃度是不會因體液擴張而受抑制。 ( D )偽性低皮質醛酮症( pseudohypoaldosteronisms (PHA))並非血中皮質醛酮濃度過低，而是腎臟對皮質醛酮有抗性，而造成類似低皮質醛酮症的表現--血鉀高。 ( B )手術切除腫瘤才能根本治療腎素瘤。