Clinical Outcomes in Patients Undergoing Laparoscopic Adrenalectomy for Unilateral Aldosterone Producing Adenoma: Partial Versus Total Adrenalectomy

Abstract

Background and Purpose:

Laparoscopic adrenalectomy is the standard treatment for patients with aldosterone producing adenoma (APA). Tthe comparative effectiveness between laparoscopic total and partial adrenalectomy remains controversial, however. In this study, we compared the clinical outcomes for the two procedures.

Methods:

We analyzed the patients with unilateral APA undergoing laparoscopic total or partial adrenalectomy during the period 2008 to 2011. All surgical procedures were performed transperitoneally. We compared the perioperative and postoperative parameters between two procedures. Clinical outcomes including serum aldosterone, renin, and potassium levels, and systolic and diastolic blood pressure (DBP) were assessed and compared at 1 year after operation.

Results:

A total of 63 cases (16 partial and 47 total adrenalectomies) were included. There were no differences with regard to age, sex, hypertension duration, and tumor size as well as preoperative blood pressure, serum aldosterone, rennin, and potassium levels between the two groups. The perioperative and postoperative outcomes such as operative time, hospital stay, blood loss, and complications were similar between the two groups. The clinical outcomes at 1-year follow-up including serum aldosterone, renin, and potassium levels and blood pressure significantly improved in both groups.

Conclusions:

Laparoscopic partial adrenalectomy is technically feasible and yields similar perioperative, postoperative, and 1-year clinical outcomes to those of total adrenalectomy for the treatment of patients with unilateral APA. A prospective randomized study with a larger sample size is needed to further prove the cost and effectiveness of the two procedures.

Introduction

Primary aldosteronism is the most common cause of surgically curable secondary hypertension and affects more than 10% of the general hypertensive population.^1,2 Gagner and associates³ first reported laparoscopic total adrenalectomy in 1992. Since then, it has become the standard method to remove adrenal mass.^4,5

Laparoscopic partial adrenalectomy for the management of aldosterone producing adenoma (APA) was first described by Walz and colleagues⁶ in 1996. Until now, previous studies indicated that laparoscopic partial adrenalectomy is technically safe; moreover, the perioperative complications and surgical outcomes were similar between total and partial adrenalectomies.^7,8 The therapeutic effects for laparoscopic total vs partial adrenalectomy on APA-related clinical manifestations remain unclear, however. The currently accepted indications for partial adrenalectomy in treating patients with APA include suspected bilateral APAs and the adenoma in a solitary adrenal gland. In such patients, total adrenalectomies would lead to the need for lifelong cortical steroid replacement and increase the risk of Addisonian crisis.⁹

In this study, not only did we examine the surgical outcomes but we also compared the clinical improvement in APA-related clinical manifestations at 1 year after laparoscopic total vs partial adrenalectomy for the treatment of patients with unilateral APA.

Methods

Data collections

From January 2008 to December 2011, we consecutively collected patients with the confirmed diagnosis of primary hyperaldosteronism. All these patients were registered in the Taiwan Primary Aldosteronism Investigation database.^10
–12 The diagnosis of APA was established according to the following diagnostic steps: (1) Screening testing of elevated plasma aldosterone concentration, suppressed plasma renin activity, and a high aldosterone to renin ratio (ARR) >35,¹³ followed by aldosterone suppression confirmatory testing; (2) CT imaging, adrenal vein sampling, or I-6-beta-iodomethylnorcholesterol scintigraphy for localization of adrenal adenoma.^11,14,15 All patients received laparoscopic total or partial adrenalectomy to obtain the pathologically proven adenoma.¹⁶ Laparoscopic total and partial adrenalectomies were performed transperitoneally as described previously.^9,16

Patients with the APA tumor at the surface of the adrenal gland according to the CT scan were selected as the candidates for partial adrenalectomy. After a thorough discussion and explanation to these candidates for partial adrenalectomy concerning the risks, benefits, and possibility of complete resection, all patients signed the informed consents.

Intraoperative identification of the tumor is essential for partial adrenalectomy to make sure of the total excision of the adrenal tumor. If the tumor cannot be clearly identified during the surgical procedure, laparoscopic total adrenalectomy would be performed. Laparoscopic partial adrenalectomy was performed by approaching the tumor directly instead of controlling the adrenal vessels as is done in standard total adrenalectomy. Only the vessels adjacent to the tumor were electrocauterized with the bipolar coagulator and then transected by harmonic scalpel. Whenever access to the tumor was adequate, the connective tissues around the normal adrenal gland were dissected as minimally as possible to preserve the blood supply to the remaining adrenal tissue (supplementary Fig. S1; supplementary data are available online at www.liebertpub.com/end).

We assessed perioperative, postoperative parameters and complications. The postoperative follow-up at 1 year included systolic and diastolic blood pressure values, serum potassium level, plasma aldosterone concentration, plasma renin activity, ARR, and the use of antihypertensive agents.

Statistics

Numeric data were analyzed using the Student t test and Mann-Whitney rank sum test. The categorical data were analyzed by chi-square test. A P value of less than 0.05 was considered to be statistically significant. We used the R software, version 2.8.1 (Free Software Foundation, Inc., Boston, MA), and the Stata software, version 12 (StataCorp, College Station, TX).

Results

A total of 63 patients with the confirmed diagnosis of APA underwent laparoscopic adrenalectomies, including 16 partial and 47 total adrenalectomies, at our hospital during the period 2008 to 2011. There were no differences in age, sex, body mass index, tumor laterality, adenoma size, duration of hypertension between partial and total adrenalectomy groups (Table 1).

Table 1.

The Demographic and Clinical Characteristics, Laparoscopic Partial Versus Total Adrenalectomy for Aldosterone Producing Adenoma

	Partial adrenalectomy (n=16)	Total adrenalectomy (n=47)	P
Male/female	7/9	21/26
Age (years)	48.5±10.9	48.7±11.3	0.96
Body mass index (kg/m²)	23.3±2.61	23.3±2.60	0.94
Left/right side	11/5	25/22	0.78
Duration of hypertension (years)	6.5±3.7	5.3±2.7	0.81
Tumor diameter (cm)	2.02±0.91	2.10±0.83	0.42
Preoperative
Systolic blood pressure (mm Hg)	150.4±26.9	155.3±23.5	0.49
Diastolic blood pressure (mm Hg)	92.1±14.0	93.7±15.7	0.72
Aldosterone (ng/dL):	57.3±24.8	54.8±37.4	0.80
Renin (ng/dL):	0.43±0.82	0.75±1.89	0.51
Potassium (mmol/L):	3.52±0.63	3.36±0.76	0.32
ARR:	2525.2±3140.1	1149.0±2948.6	0.12

ARR=aldosterone to renin activity ratio.

Table 2 lists perioperative results in both groups. All patients underwent surgical procedures successfully without conversion to open laparotomy. In addition, no major postoperative complications were observed in all study subjects.

Table 2.

Perioperative and Postoperative Outcomes, Laparoscopic Total Versus Partial Adrenalectomy

	Partial adrenalectomy (n=16)	Total adrenalectomy (n=47)	P
Operative time (minutes)	95.9±46.1	103.5±33.1	0.48
Blood loss (mL)	21.9±7.5	37.5±37.5	0.11
Hospital stay (days)	3.56±0.89	3.96±1.17	0.23
Presence of micronodules in pathology; patients (%)	5/16 (31.3%)	16/47 (34%)	0.84

There were no significant differences in terms of operative time (95.9±46.1 vs 103.5±33.1 minutes, P=0.48), blood loss (21.9±7.5 vs 37.5±37.5 mL, P=0.11), hospital stay (3.56±0.89 vs 3.96±1.17 days, P=0.23) between partial and total adrenalectomy groups. In review of the final pathology report, 21 (33%) cases revealed associated micronodules, including 5 in the partial adrenalectomy group and 16 in the total adrenalectomy group.

Table 3 shows the clinical outcomes before and 1-year after laparoscopic adrenalectomy. All of the patients in both groups showed improvement in hypertension, with decreasing antihypertensive medications. No patients needed spironolactone treatment and potassium supplement. It is worth noting that 17 (36.2%) of 47 patients undergoing total adrenalectomy remained hypertensive after operation and needed antihypertensive drugs to control hypertension. Seven (43.8%) of 16 patients in the partial adrenalectomy group needed antihypertensive drugs to control hypertension, however.

Table 3.

Clinical Outcomes at 1-year Follow-Up After Surgery, Laparoscopic Total Versus Partial Adrenalectomy

	Partial (n=16)	Total (n=47)	P
1-year follow up
Systolic blood pressure (mm Hg)	141.18±17.39	138.88±20.61	0.750
Diastolic blood pressure (mm Hg)	88.27±11.28	85.92±12.92	0.604
Aldosterone (ng/dL)	34.55±12.62	28.55±13.17	0.164
Renin (ng/dL)	2.44±3.08	3.20±5.65	0.656
Potassium (mmol/l):	4.29±0.57	4.36±0.35	0.617
ARR	87.94±104.75	42.90±79.91	0.112
Abnormal ARR; pts (%)	6/16 (37.5%)	14/47 (29.8%)	0.239

Abnormal ARR based on the ratio >35.

ARR=aldosterone to renin activity ratio.

All of the patients in both groups showed improvement in all plasma rennin activity and aldosterone level at 1 year after operation. Nevertheless, according to the criteria of hyperaldosteronism,¹⁷ 14/47 (29.8%) patients in the total adrenalectomy group and 6/16 (37.5%) in the partial adrenalectomy group remained at a high ARR at 1-year follow up. All patients had a normal serum cortisol level and did not need exogeneous steroid replacement.

Discussion

Patients with primary aldosteronism and unilateral adrenal adenoma need surgical treatment even though medical treatment is effective.¹⁸ Persistent hyperaldosteronism will yield negative effects on the cardiovascular system. Surgical removal of adenoma by laparoscopic surgery has been the standard treatment in recent decades to manage functioning adrenal APA.

Adrenal sparing surgery has been adopted in selected patients undergoing laparoscopic adrenalectomy with increasing popularity. Previous study has mentioned that APA is the most common lesion for partial adrenalectomy because it is often small and solitary, and located at the gland margin.¹⁹ Kaye and coworkers²⁰ advocated that partial adrenalectomy can be the first-line therapy for small adrenal tumors; nevertheless, partial adrenalectomy has been underused until now. In addition, some studies reported that partial adrenalectomy had comparable or even favorable perioperative outcomes compared with total adrenalectomy.^7,8,21 Consistently, our study showed similar perioperative and postoperative outcomes between partial and total adrenalectomy groups.

Because surgical outcomes for partial adrenalectomy are encouraging, clinical and functional outcomes must be critically evaluated. Our study revealed the clinical outcomes were similar at 1-year follow-up between total and partial adrenalectomy groups. Approximately two-thirds of patients with APA were hypertension-free without medications in both groups; however, approximately one-third of patients remained with an abnormal ARR in the cohort.

The long-term efficacy of partial adrenalectomy on clinical outcomes remains controversial until now. Ishidoya and colleagues⁷ that reported only 2 (6.9%) of 29 patients with hypertension failed to improve in blood pressure control after partial adrenalectomy for APA at 5-year follow-up. In contrast, Meria and associates⁵ reported that even total adrenalectomy could cure hypertension in only 58% of patients. In a prospective, randomized study to compare partial with total adrenalectomies in treating APA, Fu and coworkers⁸ reported that no tumor recurrence was noted at 96-month follow-up. Similarly, all patients in both groups showed improvement in hypertension; in addition, plasma renin activity and aldosterone returned to normal after surgery in all patient at 6-month follow-up.

In terms of the impact of adrenal cortical function after partial adrenalectomy, Brauckhoff and associates²² studied the critical size of residual adrenal tissue and recovery from impaired early postoperative adrenocortical function after bilateral partial adrenalectomy. They found that leaving at least 15% to 30% adrenal tissue is necessary to preserve sufficient adrenal function. In addition, when partial adrenalectomy is performed for small adrenal lesions, the malignancy rate is negligible, and the recurrence rate is low. Most important of all, most patients do not need the steroid supplement at follow-up.²⁰ The majority of APAs are small nodules; patients could preserve sufficient adrenal cortical function with negligible risk of malignancies after partial adrenalectomy, as we have done.

It is noteworthy that 33.3% (21/63) of our study subjects had the final pathology reports showing micronodules in resected specimens of total adrenalectomies. Isidoya and colleagues⁷ also suggested that hormonally active micronodules are likely to exist concurrently with the APA in patients with primary hyperaldosteronism. Nevertheless, the correlations need further investigation concerning the impact of micronodule in the residual adrenal tissue after partial resection on the clinical outcomes such as blood pressure, plasma renin activity, and plasma aldosterone level. The postoperative aldosterone level should be routinely examined after operation in patients with APA. The benefit of preserved adrenal tissue in partial adrenalectomy has to be weighed against a possible persistence of hyperaldosteronism, especially in patients with unilateral APA and normal contralateral adrenal glands.

There were several limitations in the present studies. First, the patient number is small. Second, the 1-year follow-up period may be too short for evaluation of long-term clinical outcomes. The normalization of blood pressure and plasma aldosterone after adrenalectomy for APA patients occurred within the first 6 months, however. One-year follow-up may be sufficient to examine these clinical outcomes.

Third, not all patients in this study received venous sampling for adrenal vein sampling, which was performed only in those for whom diagnosis was difficult. As we noted in the surgical specimens of total adrenalectomies, as high as 30% of pathologic findings showed micronodules in the adrenal gland. Adrenal vein sampling is regarded as the standard diagnostic test to be used to determine the side of aldosterone secretion in patients with hyperaldosteronism.^23,24 It remains obscure for the function of aldosterone secretion in these microscopic nodules.

Conclusions

This study showed that partial adrenalectomy is technically safe and has similar therapeutic results compared with total adrenalectomy in treating patients with unilateral adrenal APA at 1 year. A prospective randomized study with a larger sample size is needed to further prove the cost and effectiveness of the two procedures.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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