Association for Academic Surgery
Persistent hypertension after adrenalectomy for an aldosterone-producing adenoma: Weight as a critical prognostic factor for aldosterone's lasting effect on the cardiac and vascular systems

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Abstract

Background

Primary aldosteronism caused by an aldosterone producing adrenal tumor/aldosteronoma (APA), is a potentially curable form of hypertension, via unilateral adrenalectomy. Resolution of hypertension (HTN) is not as prevalent after tumor resection, as are the normalization of aldosterone secretion, hypokalemia, and other metabolic abnormalities. Here, we review the immediate and long-term medical outcomes of laparoscopic adrenalectomy in patients with an APA, and attempt to identify any distinctive sex differences in the management of resistant HTN.

Methods

We performed a retrospective review of the prospective adrenal database at the University of Wisconsin between January 2001 and October 2010. Of the 165 adrenalectomies performed, 32 were for the resection of an APA. Patients were grouped according to their postoperative HTN status. Those patients with normal blood pressure (≤120/80 mm Hg) and on no antihypertensive medication (CURE) were compared with those who continued to require medication for blood pressure control (HTN). We evaluated sex, age, body mass index, tumor size, duration of time with high blood pressure, and the differences in systolic and diastolic blood pressure following adrenalectomy. Statistical analysis was performed using Student's t-test. Statistical significance was defined as a P value of <0.05.

Results

We identified 32 patients with an APA based on biochemical and radiographic studies, two patients were excluded, due to missing data. There were 19 males (63%) and 11 (37%) females, with a mean age was 48.3 ± 2.1 y, and mean tumor size was 24 ± 3 mm. Postoperatively, patients required significantly fewer antihypertensive medications (1.5 ± 0.2 versus 3.3 ± 0.3, P < 0.001). Nine patients (31%) had complete resolution of their HTN, requiring no postoperative antihypertensive medication. The only significant difference between the sexes, was a lower body mass index in women (27.6 ± 1.7 versus 33.4 ± 2.1 kg/m2, P = 0.04). Ninety percent of the cohort had at least a 20 mm Hg decline in their systolic blood pressure postoperatively, placing them in the prehypertensive or normal blood pressure categories. Sixty-six percent of the CURE patients required at least 6 mo for resolution of their HTN. All 20 patients who presented with hypokalemia, had immediate resolution postoperatively and did not require continuance of the preoperative spironolactone or potassium supplementation.

Conclusions

Laparoscopic adrenalectomy for aldosterone producing adenoma results in the normalization of, or more readily manageable blood pressure in 90% of patients, within 6 mo. Metabolic disturbances are immediately corrected with tumor resection. Weight is an important contributing factor in resolving HTN.

Introduction

The clinical picture of hypokalemic, renin-independent primary hyperaldosteronism causing drug-resistant hypertension, was first reported by Jerome Conn in 1955 [1]. Traditionally noted to be rare, an aldosterone-producing adenoma (APA)/aldosteronoma accounts for about 60% of primary hyperaldosteronism [2]. It is the most common cause of secondary hypertension and is often underreported with an incidence of 2%–5% [3], [4], [5], [6], [7], [8]. The true incidence and prevalence are difficult to assess, due to the inconsistent inclusion of bilateral adrenal hyperplasia in the diagnosis, as well as the increasing number of hypertensive patients meeting the biochemical criteria for aldosteronism [9]. Accounting for 0.05%–2.2% of the hypertensive population, Conn's syndrome is one of the few potentially curable causes of hypertension [4], [10], [11], [12], [13], [14]. There is a growing body of evidence supporting the significant contribution that aldosterone contributes to both the development and severity of hypertension. Furthermore, prolonged exposure to aldosterone results in end organ damage and failure [2], [9].

Aldosterone most notably increases sodium absorption in the distal tubules and collecting ducts of the kidneys, resulting in increased intravascular volume and increased blood pressure. Cardiac damage results from greater ventricular septum and left ventricular wall thickness increasing myocardial oxygen demand and consumption. Excess aldosterone production by the tumor increases fibrosis in the vasculature and the intraventricular cardiac septum by increasing collagen production in these areas. Left ventricular hypertrophy, vascular remodeling with intima-media thickening, and cardiac fibrosis along with renal dysfunction as a result of renal arteriosclerosis, direct damage to nephron geometry, and function, are all potential reasons for persistent hypertension despite APA resection [15], [16], [17]. Of concern, is the fact that the effects that aldosterone have on the cardiac, renal, and vascular systems, are independent of its effects on increasing blood pressure; hence, the long-term effect of excess aldosterone exposure on these organs, warrants the prompt and correct evaluation, diagnosis, and resection of these tumors.

Focusing on APA, the goal of treatment is normalization of aldosterone levels via surgical resection, or by administering mineralocorticoid receptor antagonists to block the effects of aldosterone [2], [18]. Unilateral laparoscopic adrenalectomy is the gold standard treatment [19], [20], [21]. Spironolactone and epleronone, both mineralocorticoid receptor antagonists, effectively address hypokalemia; however, they have drawbacks, including: side effects (painful gynecomastia, decreased libido, menstrual abnormalities, and erectile dysfunction), persistent high blood pressure, and minimal or no effect on other metabolic abnormalities caused by aldosteronism. APA resection completely abolishes aldosterone hypersecretion, can result in a significant decrement in systolic blood pressure (–20 to –40 mm Hg) and can decrease the number of medications required for blood pressure management [22], [23], [24], [25]. Tumor resection results in a clinically relevant improvement in blood pressure control, and attenuated cardiac, cerebrovascular, and renal failure morbidities, even in those patients who continue to require antihypertensive medication.

The question of what lasting effect hyperaldosteronism has on the heart, brain, and kidney, has yet to be completely answered. APA resection results in immediate correction of hypokalemia and other clinical and biochemical signs of adrenal hyperfunction in 98%, but long-term blood pressure normalization is evident in only 20%–35% [23], [24], [26], [27], [28], [29], [30]. These patients are at a higher risk for myocardial infarction, cerebrovascular accident, and renal failure than other hypertensive patients. Studies have focused on the lack of resolution hypertension after tumor resection and the possible predictors of resolution. Noted predictive factors include: female sex, younger age, requiring less than three antihypertensive medications for blood pressure control, having a diagnosis of hypertension for fewer than 6 y, and adenoma size of <20 mm [24], [26], [27], [28], [31], [32]. In addition, excess aldosterone production puts patients at a higher risk of left ventricular hypertrophy, myocardial infarction, cerebrovascular accidents, and renal disease [2].

In this study, we sought to elucidate aldosterone's immediate and long-term effects on blood pressure and identify any distinctive sex advantages, in patients who underwent laparoscopic adrenalectomy for an APA.

Section snippets

Materials and methods

Between January 2001 and December 2010, 165 adrenalectomies were performed at a single institution. We retrospectively reviewed the 32 patients diagnosed with an APA who underwent unilateral adrenalectomy at our institution. Because of insufficient data, two patients were excluded from analysis. The remaining 30 patients were analyzed. A review of the University of Wisconsin Prospective Adrenal Surgery Database was performed. Institutional approval was obtained from the local institutional

Results

Of the 165 adrenalectomies performed between January 2001 and December 2010, 32 patients underwent unilateral laparoscopic adrenalectomy for an APA. Of the 30 patients analyzed, 11 (37%) were female, and the mean age was 48 ± 2 y, mean tumor size was 24 ± 3 mm and the majority (67%) presented in the left adrenal gland (Table 1). Adrenalectomy resulted in a significant decline in systolic blood pressure (161 ± 5 versus 124 ± 3 mm Hg, P < 0.001), diastolic blood pressure (100 ± 4 versus 79 ± 2 mm

Discussion

In our series, hypertension resolved at follow-up (1 d to 9.7 y) in nearly one third of patients who underwent unilateral laparoscopic adrenalectomy for an aldosterone- producing adenoma. Resolution of hypertension was associated with female sex, fewer preoperatively prescribed antihypertensive medications, and lower BMI. Our hypertension cure rate (30%) was similar to other studies in which these patients required no blood pressure medication to maintain a blood pressure ≤120/80 mm Hg [22],

Conclusion

Laparoscopic adrenalectomy for aldosterone producing adenoma results in the normalization of, or more readily manageable blood pressure in 90% of patients, within 6 mo. Metabolic disturbances are immediately corrected with tumor resection. Weight is an important contributing factor in resolving hypertension.

Acknowledgment

The authors thank Nicholas Yeutter for his contribution to the data collection and critical editing of this article.

Supported by NIH/NCI National Institutes of Health/National Cancer Institute Supplemental Grant RO1CA12115.

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