Malignant Hypertension in a Patient with Primary Aldosteronism with Elevated Active Renin Concentration

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1 CASE REPORT Malignant Hypertension in a Patient with Primary Aldosteronism with Elevated Active Renin Concentration Kiyoshi Oka, Koichi Hayashi, Tomonori Nakazato, Taichi Suzawa, Keiji Fujiwara and Takao Saruta A 40-year-old male, with a past history of hypertension but receiving no medical treatment, was referred. He manifested malignant hypertension (190/130 mmhg;keith-wagener III), renal dysfunction (serum creatinine, 3.8 mg/dl), and elevated plasma aldosterone (450 pg/ml) and active renin concentration (ARC, 104 pg/ml). His blood pressure was controlled with multiple antihypertensive agents and ARCthus decreased (4.3 pg/ml), but aldosterone remained elevated. Abdominal magnetic resonance imaging (MRI) revealed a right adrenal adenoma, and aldosterone-producing adenomawas confirmed by adrenal venous sampling. Primary aldosteronism very rarely develops to malignant hypertension, and even in that case ARCis suppressed. Therefore this is a rare case of primary aldosteronism complicated with malignant hypertension and high ARC. (Internal Medicine 36: , 1997) Key words: aldosterone, renin, renal injury, adrenal adenoma, hemolytic anemia, hypertension Introduction Primary aldosteronism is one of the most commondisorders that cause secondary forms of hypertension. In this form of hypertension, plasma renin activity is suppressed as a consequence of sodium retention. Previous reports indicate that primary aldosteronism is less likely to cause hypertensioninduced vascular damage (1-6), and is rarely complicated with malignant or accelerated hypertension (7-17). Even evolving into malignant phase, it still presents suppressed renin activity (9, ll, 12, 14, 16, 17). Here, we report a rare case with aldosterone-producing adenoma complicated with malignant hypertension. This case is noteworthy since he initially showed an elevated plasma aldosterone and active renin concentration. After appropriate medical treatment, the renin level declined, but was not suppressed below normal range. For editorial comment, see p 669. Case Report A 40-year-old man had been diagnosed as hypertension (-140/100 mmhg)in 1990, but did not receive medical treatment thereafter. In January 1 996, he noticed headache, dyspnea, and palpitation, and he was admitted to a local hospital for the treatment of hypertension ( 1 90/1 30 mmhg), renal dysfunction (serum creatinine, 3.8 mg/dl; blood urea nitrogen, 51 mg/dl), and hypokalemia (2.3 meq//). Despite an intensive treatment, his blood pressure was uncontrollable. Because of high plasma renin [active renin concentration (ARC), 104 pg/ml (normal range, pg/ml)] and plasma aldosterone concentration (450 pg/ml), he was referred to Keio University Hospital for treatment and full evaluation of intractable hypertension. On admission, physical examination revealed severe hypertension (177/133 mmhg), hypertensive retinopathy (Keith- Wagener III), and cardiomegaly, but abdominal bruit was inaudible. His laboratory data is summarized in Table 1. Serum creatinine was elevated (4.3 mg/dl), but curiously, the serum potassium concentration was reduced (3. 1 meq//). On the basis of the laboratory tests, including anemia (hemoglobin, 10.9 g/ dl), reticulocytosis (35%o), elevated lactate dehydrogenase (LDH, 681 IU//; isozyme pattern, L{ 30.3%, L2 38.8%), low haptoglobin level (<10 mg/dl), and negative Coomb's test, he was found to suffer from microangiopathic hemolytic anemia due to malignant hypertension. Endocrinological tests revealed high ARC(122 pg/ml) and plasma aldosterone concentration (252 pg/ml). Blood gas analysis indicated metabolic alkalosis (ph ) with a high bicarbonate level (27.2 meq//). Urinary excretion of potassium was increased (65. 1 meq/day) despite decreased serum potassium. His blood pressure was treated with multiple antihyperten- From the Department of Internal Medicine, School of Medicine, Keio University, Tokyo Received for publication December 26, 1996; Accepted for publication May 20, 1997 Reprint requests should be addressed to Dr. Takao Saruta, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku,Tokyo

2 Aldosteronoma and Malignant Hypertension Table 1. Laboratory Data on Admission sive agents including spironolactone, amlodipine, doxazosin, and oc-methyldopa, and it began to decline (Fig. 1). In parallel with changes in blood pressure, serum creatinine (from 4.4 to 2.1 mg/dl) and LDH (from 3,091 to 200 IU//) were decreased, and serum potassium was elevated from 2. 1 to 4.2 meq//. ARC also decreased markedly from 122 to a "normal" level of8.7 pg/ ml. Despite an intensive antihypertensive treatment and amelioration of renal function, his serum aldosterone levels remained elevated (252-1,256 pg/ml). Ultrasound examination revealed concentric left ventricular hypertrophy of the heart, and bilateral renal parenchymal damage with symmetrical renal hypoperfusion. On abdominal computed tomography (CT), right adrenal mass (size, 1.5 cm) was found. Adrenal scintigraphy (13^-cholesterol) also detected a marked accumulation on the right adrenal gland with diminished contralateral accumulation. Magnetic resonance imaging (MRI) of adrenals revealed a nodule in the right adrenal, with isointensity on the Tl-weighted image of the liver and high intensity on the T2-weighted image, a finding compatible with adrenal adenoma (Fig. 2). Both MRI-angiography and Doppler ultrasound showed no stenotic lesion of renal arteries. To clarify the nature of the right adrenal mass, adrenal venous sampling was performed (Table 2). The comparison of the aldosterone/cortisol ratio between left and right adrenal venous blood sampling clearly indicated an aldosterone-producing adenoma in the right adrenal gland. Under the diagnosis of an aldosterone-producing adenoma, an operation (retroperitoneal laparoscopic adrenalectomy) was performed on April 9, The removed adrenal contained a golden-yellow mass (20x15 mm; Fig. 3), and histological examination of the adrenal mass proved to be a clear cell-type adrenocortical adenoma. After the operation, his blood pressure gradually decreased (140/100 mmhg), requiring only smaller doses of antihypertensive agents. The serum aldosterone concentration declined sharply to 77 pg/ml, and serum creatinine was also decreased to 2.1 mg/dl. After the surgery, the serum potassium concentration was maintained constant above 3.8 meq// without potassium supplementation or spironolactone. Discussion Primary aldosteronism is characterized by extracellular volumeexpansion and the subsequent hypertension attributed to increased aldosterone production, and suppressed plasma renin 701

3 Oka et al 1-n 1 ; 1 30 Manidipine llo Nifedipine-R 60 ' ' 40 Captopril 1 5QQ ar-methyldopa 750 BP 3?5 L^ Amlodipine i ^ ^ Doxazosin 1 TTN """*»-å!å I SpironolactoneI ^n 1 (mmhg) '-----n. >s^ I rrr ^\Systolic BP/^V^^^ 25^^K LDH 1 1 3,000-i pi (LU.)< II ^^^^m^ Diastolic BP ^^ Cr (mg/dl) f- 5 1,000- ^*^*~*-^-~^^_ K(mEq//) ^ _4 - u II II n n n n rn PI r1 arc arc - S1'256 r600 -M """" \ : -(Pg/ml) (pg/ml)- pi \ Ijl II II fepj-kj Eyd ^iv-h^^^hk-tvxj t -rr;.1 ( (M^ a Jan.a Feb. Mar. a Apr. (b) Operation Figure 1. Clinical course. A: admission to a local hospital, B: admission to our hospital. Figure 2. MRIof the abdomen with Tl-weighted imaging. Arrows indicate the right adrenal tumor. 702

4 Aldosteronoma and Malignant Hypertension Table 2. Adrenal Venous Sampling ALDO:aldosterone, CORTI: cortisol, A: adrenaline, NA: noradrenaline, DA: dopamine. Figure 3. A) Macroscopicfindingsofthe rightadrenal tumor showing a golden-yellow mass (size, 20x15x10 mm). Distance between ticks indicates 5 mmin length. B) Histological examination of the right adrenal tumor showing a clear cell-type adrenocortical adenoma (HE stain, x400). activity. The renin profile is particularly useful for differentiation of the primary form from secondary aldosteronism (e.g., malignant hypertension) that exhibits an elevated plasma renin level. Traditionally, this disorder has been assumed to cause less vascular injury (1-6), probably due to suppressed angiotensin level. Actually it develops relatively less frequently to malignant or accelerated hypertension. Evenin a malignant phase, patients with primary aldosteronism are reported to manifest suppressed renin activity (9, ll, 12, 14, 16, 17). The present case reveals a unique renin profile. Initially, this patient was diagnosed as "secondary aldosteronism" resulting from malignant hypertension; both plasma renin and aldosterone were increased markedly [4-fold greater for ARCand 2- fold for aldosterone]. Despite the appropriate treatment, the serum aldosterone level still remained elevated. Further examination indicated adrenal mass, and adrenal venous blood sampling established the diagnosis as an aldosterone-producing adenomawith malignant hypertension. It has been established that although in patients with primary aldosteronism, the circulating plasma volume is increased, the plasma volume expansion reaches a certain equilibration set point above which natriuresis occurs and consequently peripheral edema does not occur (i.e., escape phenomenon). Thus, the increased extracellular volume inhibits the sodium chloride reabsorption at the proximal tubule. The reduced sodium chloride reabsorption would increase the distal delivery of sodium, and increase the sodium chloride load to the macula densa. This increased load could inhibit renin release from juxtaglomerular cells. In addition, the increased blood pressure would elevate the renal perfusion pressure, resulting in the suppression of renin release. Contrary to the traditional renin profile of primary aldosteronism, the present case manifested markedly elevated plasma renin concentration. It should be noted that the possibility exists that the elevated plasma renin concentration is attributed to renal artery stenosis, leading to renal hypoperfusion. MRIangiography, however, failed to reveal renal artery stenosis. Furthermore, renal Doppler ultrasound did not indicate the stenosis of the renal artery or its large branches, but showed bilateral renal parenchymal damage. Additionally, the present case manifested normocytic anemia, elevated LDHwith dominant L4/L2 isozymes, reduced haptoglobin level, and negative Coomb's test, suggesting microangiopathic hemolytic anemia due to extensive vascular endothelial injury. Finally, the plasma renin concentration fell to the lower limit of the normal range after the medical and surgical treatment. Although the coexistence of renal artery stenosis cannot be excluded completely, it is most likely that the progression of renal injury induced by 703

5 Oka et al malignant/accelerated hypertension and the subsequent glomerular ischemia constitute the pivotal determinant of the markedly elevated renin release. As far as we found in the literature, only three cases have been reported that manifest a similar clinical course (i.e., primary aldosteronism with malignant hypertension, renal failure, and elevated plasma renin activity) to the present case (10, 13, 15), and these cases were confirmed only by postmortem examination. Of note, all of these cases, including our case, presented clinical manifestations of malignant hypertension and progressive deterioration of renal function during relatively short periods. Although renal injury and glomerular ischemia may predispose the renin profile to elevation, this premise does not necessarily apply to primary aldosteronism. Thus, Obanaet al (18) previously reported a case of primary aldosteronism in which preexisting chronic glomerulonephritis developed relatively slowly to a stage of renal insufficiency. In this case, however, plasma renin activity had been suppressed, which increased to a normal level after operation. Furthermore, Inaba et al ( 19) showed a reduced plasmarenin activity in the presence of renal insufficiency in a patient with bilateral adrenal adenoma. Thus, although the renal injury is required for the elevated renin activity, it does not fully explain the increase in plasma renin activity. Additional factors would act in concert with renal injury to cause the enhanced renin activity in primary aldosteronism; the rate of the progression of renal injury may participate in the enhanced renin profile. Alternatively, the acute exacerbation of renal function could be a precipitating factor for the development of malignant hypertension. In summary, we have described a rare case of primary aldosteronism with malignant hypertension and rapidly progressive renal dysfunction. The present case is of particular note since active renin concentration is markedly elevated rather than suppressed. This paradoxical rise in renin activity would veil the original hormonal characteristics observed in primary aldosteronism, and should therefore be born in mind when hypertension develops to a malignant phase. The diagnosis of this curable hypertension would offer better quality of life and prognosis for these patients. References 1) Conn JWPart I, Painting background Part II, Primary aldosteronism, a new clinical syndrome. J Lab Clm Med 43: 3, ) Conn JW. Aldosteronism in man; Some clinical and climatological aspects, Part II. JAMA 183: 871, ) Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases. AmJ Surg 107: 159, ) Conn JW, Cohen ED, Rovner DRSuppression of plasma renin activity in primary aldosteronism. Distinguishing primary from secondary aldosteronism in hypertensive disease. JAMA190: 213, ) Conn JW, Cohen ED, Rovner DR, Nesbit RM. Normokalemic primary aldosteronism A detectable cause of curable "essential" hypertension. JAMA 193: 200, ) Laragh JH. Vasoconstnction-volume analysis for understanding and treating hypertension* the use ofremn and aldosterone profiles AmJ Med 55: 261, ) Kaplan NM. Primary aldosteronism with malignant hypertension. N Engl J Med269:1282, ) Del Greco F, Dolkart R, Skom J, Method H. Association of accelerated (malignant) hypertension in a patient with primary aldosteronism. J Clin Endocnnol Metab 26: 808, ) McAllister RG Jr, Van Way CW, Dayani K, et al. Malignant hypertension: Effect of therapy on renm and aldosterone. Circ Res 28: Suppl 2: 160, ) Baglin A, Weiss Y, Safar M, Milhez P. Hyperaldosteronisme pnmaire avec hypertension maligne. La Nouvelle Presse medicale 2: 295, 1973 (in French). 1 1) Aloia JF, Beutow G. Malignant hypertension with aldosteronoma producing adenoma. Am J Med Sci 268: 241, ) Baxter RH, Wang I. Malignant hypertension in a patient with Conn's syndrome. Scott Med J 19: 161, ) Iyon S, Saruta T, Kondo K, Ozawa Y, Hata J, Shimizu K. Renin and juxtaglomerular apparatus in a patient with primary aldosteronism complicated by chronic renal failure. South Med J 69: 951, ) Murphy BF, Whitworth JA, Kincaid-Smith P. Malignant hypertension due to an aldosterone producing adrenal adenoma. Clm Exp Hypertens [A] 7: 939, ) Iwaoka T, Umeda T, Sato T, Katsuragi S, Takeuchi T. High plasmarenin activities in primary aldosteronism with malignant hypertension. A case report. Jpn Heart J 21: 423, ) Bravo EL, Fouad-Tarazi FM, Tarazi RC, Pohl M, Gifford RW, Vidt DG. Clinical implications of primary aldosteronism with resistant hypertension. Hypertension ll: 1207, ) Sunman W, Rothwell M, Sever PS. Conn's syndrome can cause malignant hypertension. J Hum Hypertens 6: 75, ) Obana M, Hayakawa Y, Higashi F, et al. A case of primary aldosteronism with chronic renal failure (author's transl). Nippon Jmzo Gakkai Shi 22: 51, 1980 (in Japanese). 19) Inaba M, Nakamura K, Isogai S, et al A case report of primary aldosteronism with bilateral multiple adrenal adenoma Nippon Naika Gakkaishi 66: 128, 1977 (Abstract in Japanese). 704 Internal Medicine Vol. 36, No 10 (October 1997)