RE: PHEOCHROMOCYTOMA COEXISTING WITH RENAL ARTERY LESIONS

0022-5347/01/1656-2005/0 THE JOURNAL OF UROLOGY® Copyright © 2001 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 165, 2005–2008, June 2001 Printed in U.S.A.

Letters to the Editor RE: PHEOCHROMOCYTOMA COEXISTING WITH RENAL ARTERY LESIONS I. S. Gill, A. M. Meraney, E. L. Bravo and A. C. Novick J Urol, 164: 296 –301, 2000 To the Editor. The authors state that pheochromocytoma can rarely coexist with renal artery stenosis and that the former can mask the signs and symptoms of the latter. Whether renal artery stenosis was responsible or contributory to hypertension in these patients is uncertain as there was no clear correlation between pathological findings and renal vein renins. Also, other mechanisms leading to renal artery stenosis, such as external compression, catecholamine induced vasospasm and clinically insignificant narrowing of the renal artery, were not excluded from the analysis. By suggesting that renal artery stenosis should be routinely considered a coexistent lesion with renal hilar pheochromocytoma, the authors risk over testing and potentially overtreating patients. During the 47-year period of this study in 269 patients only 10 cases of coexistent pheochromocytoma and renal artery stenosis were noted. Closer examination reveals that 1 case was actually a renal artery aneurysm and another was iatrogenic angiographic dissection. A total of 3 other cases were suspected because the pheochromocytoma externally compressed the renal artery, which could be surmised by the tumor location alone, and these cases were corrected by tumor removal. The actual number of pheochromocytomas compressing the renal artery was not stated. Thus, the definite number of patients in whom the presence of renal artery stenosis was unexpected is small. It is important to remember that not all renal artery stenoses lead to hypertension. Most stenoses, even those documented by angiography, are not functionally significant and do not cause renovascular hypertension or damage renal function. Thus, it would be a mistake to assume that all arterial lesions reported in this study, many of which may have been potentially reversible by pheochromocytoma removal, warranted treatment. The sensitivity and specificity of renal artery stenosis testing in these patients is not stated, and it appears that only 3 of an undetermined number of those with renal hilar pheochromocytoma were actually evaluated with plasma and renal vein renins. The criteria for initiating an evaluation for renal artery stenosis included 1) increased serum creatinine, 2) increased plasma renin activity, 3) small kidney (not defined), 4) calcified renal artery, 5) extra-adrenal tumor at the renal hilum and 6) large inferior pole adrenal mass impinging on the renal hilum. Increased serum creatinine is common and may be caused by hypertension. This criterion will result in many unnecessary evaluations for renal artery stenosis. Concerning the second criterion, the authors state that “hyperreninemia cannot be interpreted as conclusive evidence of renal artery stenosis in patients with a pheochromocytoma.” Regarding criteria 3 and 4, a small kidney or renal artery calcifications correlate poorly with renal artery stenosis.1, 2 Modern recommendations for evaluation of renal artery stenosis exclude these nonspecific findings as risk factors.3– 6 The last 2 criteria are virtually identical and ignore the possibility of direct evaluation of the renal artery during surgery. Thus, we fear that implementation of these criteria may increase the expense and perhaps the morbidity of the preoperative evaluation of pheochromocytoma without contributing to patient outcome. The authors discuss the well documented physiological phenomena of catecholamine induced arterial constriction, resulting from local leakage of vasoactive catecholamines from an adjacent pheochromocytoma into the renal hilum. This pseudostenosis has been reported to resolve after the patient is placed on ␣-blockade to block the local vasoconstrictive effects of catecholamines. Removal of the pheochromocytoma has also been shown to resolve this narrowing.7, 8

The questionable clinical significance of any renal artery stenosis in this setting has been well exemplified in a normotensive patient who had a small kidney with clinically insignificant renal artery stenosis remaining after removal of a hilar pheochromocytoma.9 Traditionally, ␣ and ␤ blockade have been used preoperatively in patients undergoing surgery for pheochromocytoma. The addition of metyrosine to the blockade depletes the amount of catecholamines in the tumor, and is thought to ease anesthetic management to a greater extent.10 A disadvantage of this blockade is the 10-day to 2-week waiting period required for affect. The Cleveland Clinic has long been an advocate of calcium channel blockade in the preoperative preparation of patients with pheochromocytoma for surgery.11 An advantage is that this type of blockade allows faster patient preparation for surgery and, thus, minimizes the need for the patient to travel home to wait for adequate blockade. We cannot help but wonder if this treatment strategy may increase the diagnosis of apparent renal artery stenosis because of the lack of ␣-blockade use. Although rare, the problem of coexistent pheochromocytoma and renal artery stenosis is difficult. We agree that clinicians must be aware of the coexistence of these 2 lesions but suggest that judicious use of magnetic resonance or computerized tomography angiography during the initial workup could eliminate the need for the suggested extensive evaluation with Doppler ultrasound, captopril renography and angiography.12 Since treatment for renovascular hypertension is usually based on angioplasty and stents, it may also be reasonable simply to treat pheochromocytoma surgically, and if hypertension persists additional testing for renovascular hypertension should be initiated. Respectfully, McClellan M. Walther and Peter L. Choyke Urologic Oncology Branch National Cancer Institute Department of Radiology Clinical Center National Institutes of Health 10 Center Dr., MSC 1502 Bethesda, Maryland 20892-1502

1. Gayard, P., Garcia, J. M., Boire, J. Y. et al: Spiral CT quantification of aorto-renal calcification and its use in the detection of atheromatous renal artery stenosis: a study in 42 patients. Cardiovasc Intervent Radiol, 23: 17, 2000 2. Siegel, C. L., Ellis, J. H., Korobkin, M. et al: CT-detected renal artery calcification: correlation with renal artery stenosis on angiography. AJR Am J Roentgenol, 163: 867, 1994 3. Aurell, M. and Jensen, G.: Treatment of renovascular hypertension. Nephron, 75: 373, 1997 4. Conlon, P. J., O’Riordan, E. and Karla, P. A.: New insights into the epidemiologic and clinical manifestations of atherosclerotic renovascular disease. Am J Kidney Dis, 35: 573, 2000 5. National High Blood Pressure Education Program Working Group: 1995 update of the working group reports on chronic renal failure and renovascular hypertension. Arch Int Med, 156: 1938, 1996 6. Dustan, H. P.: Renal arterial disease and hypertension. Med Clin North Am, 81: 1199, 1997 7. Camberos, A., Bautista, N., Rubenzik, M. et al: Renal artery stenosis and pheochromocytoma: coexistence and treatment. J Pediatr Surg, 35: 714, 2000 8. Hill, F. S., Jander, H. P. and Murad, T.: The co-existence of renal artery stenosis and pheochromocytoma. Ann Surg, 197: 484, 1983 9. Raghavaiah, N. V. and Singh, S. M.: Extra-adrenal pheochromocytoma producing renal artery stenosis. J Urol, 116: 243, 1976 10. Walther, M. M., Keiser, H. R. and Linehan, W. M.: Pheochromocytoma: evaluation, diagnosis and treatment. World J Urol, 17: 35, 1999 11. Ulchaker, J. C., Goldfarb, D. A., Bravo, E. L. et al: Successful outcomes in pheochromocytoma surgery in the modern era. J Urol, 161: 764, 1999 2005

2006

LETTERS TO THE EDITOR

12. Prince, M. R., Schoenberg, S. O., Ward, J. S. et al: Hemodynamically significant atherosclerotic renal artery stenosis: MR angiographic features. Radiology, 205: 128, 1997

Reply by Authors. Walther and Choyke fail to note that our report is a review of pheochromocytoma coexistent with renal artery lesions. These lesions include not only stenosis of the renal artery, but also other lesions of the renal artery, such as aneurysms and iatrogenic dissection of the renal artery, which have the propensity to cause secondary hypertension (reference 3 in letter). Furthermore, information related to stenoses caused by external compression or catecholamine induced pseudostenosis is important to the reader because stenoses pose not only a diagnostic dilemma, but also correction of both coexistent lesions can be effectively achieved by pheochromocytoma excision alone. As we reported, it is obvious that the functional significance of an anatomical stenosis of the renal artery must be confirmed to qualify for treatment. A literature search revealed that 31 of 87 cases (36%) of pheochromocytoma had extrinsic renal artery compression, which is a significant cause of coexistent renal artery stenosis, albeit in a limited patient population (ectopic tumors comprise 10% of all pheochromocytoma cases, of which renal hilar tumors are a subset). In addition to excluding the presence of a coexistent lesion, detailed investigation of these cases also provides a valuable map for precise exploration of the renal hilum. In table 1 we clearly mentioned the pathogenesis and treatment of each case in our series. Of 10 patients 3 had coexistent renal artery stenosis due to extrinsic compression. The criteria that we listed are pointers for suspecting an additional cause of secondary hypertension in patients already diagnosed with this condition (pheochromocytoma). We caution that recommendations for evaluating renal artery stenosis in the general population should be distinguished from criteria for evaluating concomitant renal artery lesions in patients already diagnosed with pheochromocytoma (references 5, 6 in letter). For example, in our experience increased serum creatinine is uncommon in patients with sporadic pheochromocytoma. The objectives of evaluating patients with pheochromocytoma for coexistent renal artery lesions are to detect and treat causes of secondary hypertension, if coexistent, and to prevent possible renal demise in patients with pheochromocytoma. It is incorrect to assume that increased serum creatinine in this clinical setting is likely due to hypertensive nephropathy without evaluating for other causes of ischemic nephropathy. We believe that saving even 1 patient with a dual lesion from long-term dialysis is worth every effort. The tests that we suggested for initial evaluation of these patients include a judicious combination of color Doppler, captopril renography and magnetic resonance angiography.1, 2 These well accepted tests are used for the initial evaluation of renal artery stenosis. The tests are essentially noninvasive and, thus, do not significantly increase patient morbidity. During a period of 47 years at our tertiary referral center, we reported 269 pheochromocytomas, which is an average of 5.3 cases per year. A small subset of these patients (3.7%) met our screening criteria and were recommended for further evaluation for renal artery stenosis. Is the evaluation of these few patients such an immense economic burden on our health care system that we can accept the occurrence of preventable, irreversible renal damage in this subgroup? Pseudostenosis or transient renal artery stenosis results from local vasoconstriction due to local hypersecretion of catecholamines. In this scenario the use of preoperative blockers not only controls blood pressure, but also reverts the stenosis. As mentioned clearly in our report, preoperative ␣-blockers are recommended in this setting as a diagnostic as well as a therapeutic tool. Finally, as stated previously we agree that minimally invasive alternatives, such as laparoscopic adrenalectomy and percutaneous renal angioplasty, have the potential to improve management of these difficult cases. 1. Setaro, J. F., Saddler, M. C., Chen, C. C. et al: Simplified captopril renography in diagnosis and treatment of renal artery stenosis. Hypertension, 18: 289, 1991 2. Bongers, V., Bakker, J., Beutler, J. J. et al: Assessment of renal artery stenosis: comparison of captopril renography and gadolinium enhanced breath-hold MR angiography. Clin Radiol, 55: 346, 2000

RE: INFLUENCES ON RENAL FUNCTION IN CHRONIC SPINAL CORD INJURED PATIENTS K. J. Weld, B. M. Wall, T. A. Mangold, E. L. Steere and R. R. Dmochowski J. Urol., 164: 1490 –1493, 2000 To the Editor. Problems associated with bladder management in chronic spinal cord injury cases remain a concern despite recent progress in the medical care of this population. Several risk factors for deterioration in renal function are particularly relevant in spinal cord injury, including level and duration of injury, amyloidosis, stone formation, reflux uropathy and chronic pyelonephritis.1 Patients with spinal cord injury also have a decrease in estimated renal plasma flow with age.2 The Foley catheter is considered a last resort for bladder management at many institutions. A number of studies have indicated increased complication rates,3–5 although it has also been reported that indwelling catheters do not cause increased complication rates.6 Patients may be switched to a Foley catheter when they are no longer able to cope with a previous method or show signs of deterioration. Anecdotally, indwelling catheters are often used in patients in poor general health who tend to be older and at increased risk for comorbid conditions. The authors studied potential upper urinary tract consequences of different methods of bladder care. The bladder management groups in this study were not controlled for risk factors for upper tract deterioration. Cases managed with Foley catheterization had a significantly greater mean age and duration of injury, and a higher incidence of vesicoureteral reflux and upper tract imaging abnormalities. In addition, patients using spontaneous voiding who failed specific criteria were transferred to another group. Thus, treatment failure was effectively discounted, reflecting favorably on the spontaneous voiding group to the detriment of other groups. An association between Foley catheterization and renal deterioration is demonstrated clearly, and it may be correct to conclude that the former may contribute to the latter. However, the presence of confounding variables means that worsening renal function cannot be attributed definitely to urethral catheterization. The possibility that the Foley catheter may help to slow the rate of decline in upper tract function should be considered.

1. 2. 3. 4. 5. 6.

Respectfully, Marcus J. Drake Department of Surgery The Medical School University of Newcastle Newcastle upon Tyne, NE2 4HH United Kingdom Price, M., Kottke, F. J. and Olson, M. E.: Renal function in patients with spinal cord injury: the eighth year of a ten-year continuing study. Arch Phys Med Rehabil, 56: 76, 1975 Jackson, A. B. and DeVivo, M.: Urological long-term follow-up in women with spinal cord injuries. Arch Phys Med Rehabil, 73: 1029, 1992 Chao, R., Clowers, D. and Mayo, M. E.: Fate of upper urinary tracts in patients with indwelling catheters after spinal cord injury. Urology, 42: 259, 1993 Jacobs, S. C. and Kaufman, J. M.: Complications of permanent bladder catheter drainage in spinal cord injury patients. J Urol, 119: 740, 1978 Morita, H., Sazawa, A., Kanno, T. et al: Long term urinary prognosis of cervical cord injury patients. Paraplegia, 32: 30, 1994 Dewire, D. M., Owens, R. S., Anderson, G. A. et al: A comparison of the urological complications associated with long-term management of quadriplegics with and without chronic indwelling urinary catheters. J Urol, 147: 1069, 1992

RE:

99m TECHNETIUM DIMERCAPTO-SUCCINIC ACID RENAL SCINTIGRAPHY ABNORMALITIES IN INFANTS WITH STERILE HIGH GRADE VESICOURETERAL REFLUX

H. T. Nguyen, S. B. Bauer, C. A. Peters, L. P. Connolly, R. Gobet, J. G. Borer, C. E. Barnewolt, P. L. Ephraim, S. T. Treves and A. B. Retik J Urol, 164: 1674 –1679, 2000 To the Editor. The authors observed a significant incidence of renal abnormalities in infants with high grade reflux and no urinary tract