The Simultaneous Occurrence of Renal Artery Stenosis and an Aldosteronoma in a Patient With Hypertension

The Simultaneous Occurrence of Renal Artery Stenosis and an Aldosteronoma in a Patient With Hypertension KathyLee Santangelo, MD, Joseph Y. Cheung MD, PhD, Robert A.M. Gifford, MD, Brian L. Thiele, MD, and Harold C. Yang, MD, PhD • The simultaneous occurrence of renovascular hypertension and an adrenocortical adenoma is a rare entity. The case of a 64-year-old woman who underwent an aortorenal bypass graft for renovascular hypertension requiring a multidrug antihypertensive regimen is presented. Persistently elevated blood pressures in the postoperative period prompted further workup for other causes of hypertension. Laboratory evaluation showed hyperaldosteronism and hyporeninemia despite enalapril administration. Abdominal computerized tomography (CT) revealed a left adrenal mass which, on surgical removal, was found to be a cortical adenoma. Subsequently, her antihypertensive therapy has been reduced to a single agent. Previous authors have described only four patients with malignant hypertension who had the rare clinical combination of renal artery stenosis and an aldosteronoma. This case reemphasizes the critical need for a thorough search for other surgically correctable lesions in those patients who remain severely hypertensive after the "definitive" operation. © 1989 by the Nat/onal Kidney Foundation, Inc. INDEX WORDS: Conn's syndrome; aldosteronoma; renal artery stenosis; hypertension.

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ONN FIRST DESCRIBED the clinical syndrome of primary aldosteronism in 1955 based on the metabolic studies in a 34-year-old white female. I -3 By 1964, he speculated that as many as 20 % of patients with essential hypertension could be cured by removal of an aldosteronesecreting adrenocortical tumor, further suggesting the possibility of hypertension resulting from combined arteriosclerosis or fibromuscular hyperplasia of the renal artery and primary aldosteronism. 4-5 Since 1955, four cases of the simultaneous occurrence of an adrenocortical adenoma and renal artery stenosis have been reported. We now report a patient with hypertension on the basis of both a renovascular stenosis and an aldosterone-producing adrenal adenoma. The previously reported cases in the literature will be reviewed and contrasted with our current patient. CASE REPORT An obese 64-year-old white woman with adult-onset diabetes mellitus, coronary artery disease, and a l6-year history of well-controlled hypertension presented to a local hospital with

From the Departments of Surgery and Medicine, The MillOn

S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey. Address reprint requests to Harold C. Yang, MD, PhD, Section of Transplantation , Department of Surgery, The M.S. Hershey Medical Center, PO Box 850, Hershey, PA 17033. © 1989 by the National Kidney Foundation, Inc. 0272-638618911406-0012$3.0010

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complaint of dizziness and a blood pressure of 250/150 mm Hg. Initial laboratory studies were remarkable for a blood urea nitrogen (BUN) of9 .6 mmol/L (27 mg/dL), acreatinine of 132 J'mollL (1 .5 mg/dL), and a potassium of 3.3 mmollL. A computerized tomographic (CT) scan of the brain was negative, and the creatinine clearance was 0.5 mLls (30 cc/min). Renal ultrasound demonstrated a small left kidney (8.5 cm) and a normal-sized right kidney (11.3 cm). Medical management failed to provide adequate blood pressure control. Two weeks later, she was transferred to The Milton S. Hershey Medical Center of The Pennsylvania State University College of Medicine on captopril 50 mg three times daily, clonidine 0.3 mg twice daily, minoxidil 7.5 mg twice daily, spironolactone 25 mg twice daily, and Transderm-Nitro (nitroglycerin; cmA Pharmaceutical Co, Summit, NJ) 5 mg four times daily. On arrival , she was found to be in acute renal failure with a BUN of 27.5 mmollL (77 mg/dL) and creatinine of 292 J'mollL (3.3 mg/dL) . Physical examination showeda blood pressure of 190/104 mm Hg and the presence of bilateral carotid and femoral bruits and a right flank bruit. Captopril was withdrawn, and her creatinine immediately began to return toward baseline. Digital subtraction angiography demonstrated occlusion of the left renal and inferior mesenteric arteries and a high-grade (> 90 %) stenosis at the orifice of the right renal artery. Renal vein renins lateralized to the right kidney (right, 53.8 ng/mL, left, 37.5 ng/mL, ratio, 1.43). Peripheral vein renins averaged 23.7 ng/mL, and the serum aldosterone level was 1.94 nmollL (69.8 ng/dL) . She underwent right aortorenal vein bypass grafting and left nephrectomy_ Postoperatively her creatinine clearance improved to 1.0 mLls (57 mLlmin), and her blood pressure was controlled medically. Three months after surgical correction, her blood pressure became progressively more difficult to control despite the addition of antihypertensives. She was readmitted seven months later with blurred vision and uncontrolled hypertension of 230/ 135 mm Hg. Antihypertensive medications included enalapril 10 mg twice daily, clonidine 0.2 mg three times daily, labetalol 300 mg twice daily, furosemide 20

American Journal of Kidney Diseases, Vol XIV, No 6 (December), 1989: pp 520-523

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RENAL ARTERY STENOSIS AND ALDOSTERONOMA mg daily, and potassium 24 mEq daily. Laboratory studies showed a BUN of9.6 mrnollL (27 mg/dL) , a creatinine of 132 /Lmol /L (1.5 mg/dL), and a potassium of 3.8 mrnol/L. Duplex ultrasonography demonstrated patency of the right aortorenal bypass graft. Peripheral vein renins were less than 1.0 ng/mL, but the aldosterone level was 3.01 nmol/L (108.5 ng/dL) despite angiotensin converting enzyme (ACE) blockade. A CT scan and magnetic resonance imaging (MRI) of the abdomen confirmed a focal mass of the right adrenal gland. Plasma cortisol, norepinephrine, epinephrine, dopamine , and urinary vanillylmandelic acid (VMA) were normal. She underwent partial right adrenalectomy with resection of a cortical adenoma. Postoperatively, her blood pressure was decreased to 160170 mrn Hg. Pathology demonstrated an adrenocortical adenoma. At discharge, antihypertensive therapy consisted of only nifedipine 20 mg four times daily, atenolol 100 mg daily, and furosemide 20 mg daily. The aldosterone level was 0. 15 nmollL (5.4 ng/dL) 1 month postoperatively, and she no longer requires potassium supplementation.

DISCUSSION

Although Conn initially speculated that 20 % of the hypertensive population could be cured by surgical removal of an aldosterone-producing adrenal tumor, S current data show that only 5 % to 10% of hypertensive patients have surgically correctable lesions. 6 This subpopulation generally comprises patients with coarctation of the aorta, renovascular hypertension, or adrenal pathology. The prevalence of renovascular hypertension in the general hypertensive population has been estimated to be around 5 %,7 whereas that of primary aldosteronism is approximately 0.7 %.8 Because these are independent events, the probability of coexistence of renovascular disease and primary aldosteronism in the same hypertensive patient can be theoretically estimated to be extremely low (0.00035), which may explain why only four hypertensive patients with concomitant renal artery stenosis and aldosteronoma have been reported. 9· 12 Table 1.

These four cases and our present case are summarized in Table 1. Our patient had a 16-year history of well-controlled hypertension before blood pressure management became increasingly difficult. In older patients with a history of well-controlled hypertension and evidence of atherosclerotic vascular disease elsewhere, the acute development of uncontrolled hypertension strongly suggests the diagnosis of critical renal artery stenosis. However, the mere presence of diffuse arteriolar sclerosis in the renal arteries, as in the case report by Hoet and Molineaux, is insufficient to describe the cause of hypertension as renovascular. 9 Fortynine percent of patients found to have moderate to severe renal artery stenosis at autopsy are normotensive during life. 13 In our patient, arteriography confirmed the presence of severe anatomic renovascular disease. The observation that our patient developed acute renal failure after being placed on captopril, and its rapid reversal on withdrawal of the drug, strongly suggests that her renal artery stenosis was functionally significant. 14 In our patient, renal vein renins lateralized to the affected kidney, predicting a surgical cure rate of 93 % . IS The fact that the beneficial effect of surgery was short-lived prompted us to search for another cause of hypertension. The progressive increases in blood pressure together with persistent hypokalemia suggested adrenal pathology. Indeed, CT scan confirmed the presence of an adrenal mass. In addition, her persistently low renin and high aldosterone levels despite full-dose ACE blockade strengthened the diagnosis , because adrenal adenomas suffer from a lack of normal renin-angiotensin II regulation. 8 In this light, it is interesting to note that a high aldosteronelrenin ra-

Reported Cases of Concomitantly Occurring Renovascular Hypertension and Adrenal Adenoma

Author

Age/Sex

Renal Lesion

Hoet and Molineaux, 1960 Laidlaw et ai, 1960 Mills et ai, 1980

54/M 55/M 41/F

Vircburger et ai, 1984

351M

Arteriolar sclerosis Left renal occlusion Bilateral renal artery stenosis Right renal artery stenosis

Present report

64/F

Left renal artery occlusion Right renal artery stenosis

Adrenal Lesion

Left adenoma Left adenoma Right adenoma

Operation Performed

Outcome

None Death Bilateral adrenalectomy Death Right adrenalectomy Normotensive

Bilateral adenomata Left adrenalectomy Normotensive Right adrenalectomy Right nephrectomy Right adenoma Right aortorenal bypass Normotensive Left nephrectomy Right adrenalectomy

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tio (> 50) after administration of captopril has been advocated as a highly specific test (100 %) for adrenal adenomas. 16 Because this test was first documented in 1983, none of the previous reports have included this value. Our patient had an aldosterone/renin ratio of > 100 while taking enalapril. The adrenal adenoma in our patient was functionally significant in that subsequent resection of the adrenal adenoma cured her hypertension and hypokalemia. Our case report is different from the previous ones listed in Table 1, which all demonstrate the presence of a renal artery stenosis and an adrenal adenoma, but fail to show in a convincing manner that both lesions contribute to their patients' hypertension. For example, in the report by Mills et al, II the unsuppressed plasma renin activity despite high circulating aldosterone levels and the dramatic clinic response after renal artery denervation strongly suggest that the renal artery stenosis, and not the adrenal adenoma, was responsible for the patient's hypertensive disorder. The patient reported by Laidlaw et al lO most likely had adrenal rather than renovascular pathology as the underlying cause of the patient's malignant hypertension because (1) the patient's blood pressure was normal as recent as 6 weeks prior to presentation, whereas ischemic changes of the left kidney were long-standing, and (2) the thrombus in the occluded left renal artery was organized. The chronology of the patient's hypertensive disease as reported by Vircburger et al l2 is most consistent with persistent right renal artery stenosis with resultant

hyperreninemic hyperaldosteronism. By contrast, our patient initially had severe renal artery stenosis, hyperreninemic hyperaldosteronism and suffered acute renal failure after treatment with captopril. In addition, her blood pressure was controlled for 3 months after aortorenal bypass and left nephrectomy. These observations suggest anatomic renovascular pathology was predominantly the initial cause of her hypertension. Her subsequent redevelopment of accelerated hypertension was associated with persistent hypokalemia and clearly suppressed plasma renin activity, indicating primary aldosteronism as the cause of the hypertension at this stage. Indeed, this was confirmed by the cure of her hypertensive disorder after adrenalectomy. SUMMARY

This case report documents the simultaneous occurrence, albeit rare, of both renovascular hypertension and primary aldosteronism as the etiology for malignant hypertension. In a patient whose hypertension has not been ameliorated by renal revascularization, in association with persistent hypokalemia, we recommend that an adrenal cortical adenoma should be seriously pursued as the cause of the hypertensionY In addition, a persistently high aldosterone-renin ratio after ACE inhibition can be used as a simple test for detecting functional adrenal adenomas. 16 ACKNOWLEDGMENT The authors thank Jean Heisey for the preparation of the manuscript.

REFERENCES 1. Conn JW: Presidential Address. Part II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med 45:6-17, 1955 2. Conn JW: Progress Report. Primary aldosteronism. J Lab Clin Med 45:661-664, 1955 3. Conn Jw, Louis LH: Primary aldosteronism, a new clinical entity. Ann Intern Med 44:1-15, 1956 4. Conn JW, Cohen EL, Rovner DR: Suppression of plasma renin activity in primary aldosteronism. JAMA 190:213-221, 1964 5. Conn JW: Plasma renin activity in primary aldosteronism. JAMA 190:222-225, 1964 6. Foster JH: Surgically correctable hypertension, in Schwartz SI, Shires GT, Spencer FC, et al (eds): Principles of Surgery, chap 23. New York, NY, McGraw-Hill, 1979, pp 10031019 7. Gifford R: Evaluation of the hypertensive patient with emphasis on detecting curable causes. Milbank 47: 170, 1969

8. Cain Jp, Thck ML, Williams GH, et al: The regulation of aldosterone secretion in primary aldosteronism. Am J Med 53:627-637, 1972 9. Hoet 11, Molineaux L: Conn's syndrome. The effect of amphenone. Acta Endocrinol 33:375-387, 1960 10. Laidlaw JC, Yendt ER, Gornall AG: Hypertension caused by renal artery occlusion simulating primary aldosteronism. Metabolism 9:612-623, 1960 11. Mills IH, Cook RF, Galley JM, et al: Corticosteronesecreting tumours: with and without renal artery stenosis. Clin Endocrinol 13:355-360, 1980 12. Vircburger MI, Todorovic P, Peric LA, et al: Renovascular hypertension associated with bilateral aldosteronoma. Postgrad Med J 60:533-536, 1984 13. Holley KE, Hunt JC, Brown AL, et al: Renal artery stenosis. A clinical-pathologic study in normotensive and hypertensive patients. Am J Med 37:14-22, 1964 14. Hricik DE, Browning PJ, Kopelman R, et al: Captopril-

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induced renal insufficiency in patients with bilateral renal artery stenoses or renal artery stenosis in a solitary kidney. N Engl J Med 308:373-376, 1983 15. Marks LS, Maxwell MH: Renal vein renin. Value and limitations in the prediction of operative results. Urol Clin North Am 2:311, 1975

523 16. Lyons DF, Kern DC, Brown RD, et al: Single-dose captopril as a diagnostic test for primary aldosteronism. I Clin Endocrinol Metab 57:892-896, 1983 17. Melby IC, Dale SL: Adrenocorticosteroids in experimental and human hypertension. J EndocrinoI81 :93-106, 1979