Factors affecting clinical outcomes of minimally invasive adrenalectomy for unilateral primary aldosteronism: a single-center retrospective cohort study

Introduction

Primary aldosteronism (PA) is a form of endocrine hypertension characterized by excessive plasma aldosterone concentrations and suppressed plasma renin concentrations (1). Aldosteronism is categorized into unilateral and bilateral. A study has shown that unilateral aldosteronism responds well to adrenalectomy, but bilateral aldosteronism still requires additional mineralocorticoid receptor antagonist (MRA) therapy (1). The Primary Aldosteronism Surgical Outcomes (PASO) study is an international program that develops consensus standards for adrenalectomy outcomes and follow-up in unilateral primary aldosteronism (UPA) (2). However, there is wide variability in the complete clinical success (CCS) of surgical treatment of UPA. Early identification of clinical characteristics affecting a patient’s postoperative hypertension remission is critical to developing a postoperative follow-up plan. Therefore, this study aimed to investigate the factors that influence clinical success after UPA and that may affect postoperative clinical outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-176/rc).

Methods

Using our hospital’s electronic medical record system, we retrospectively collected clinical data of patients who underwent minimally invasive adrenalectomy (MIA) for UPA from January 2018 to January 2023. We also followed up to observe their postoperative blood pressure normalization and potassium level correction, to explore clinical outcomes of treatment for PA. The information collected included: gender, age, body mass index (BMI), maximum tumor diameter, tumor location, surgical method, pathology type, duration of hypertension, previous use of antihypertensive medicine, preoperative and postoperative blood pressure, blood potassium, and aldosterone to renin ratio (ARR). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Shanxi Bethune Hospital (No. SBQLL-2019-092) and informed consent was taken from all the patients.

Inclusion criteria were based on the 2016 American Endocrine Society Clinical Guidelines for PA, and the 2020 European Society of Hypertension Consensus for PA: (I) positive initial plasma ARR screening confirmed by one confirmatory test (saline loading test or captopril test); or (II) patients with comorbid spontaneous hypokalemia, renin below the detectable level of our center, and aldosterone >20 ng/dL were directly included.

Preoperative PA diagnosis required persistent hypertension with or without hypokalemia (<3.5 mmol/L), elevated serum aldosterone concentration (≥310 pg/mL), suppressed plasma renin concentration (≤4 pg/mL), and ARR ≥30. Blood samples were obtained after ≥2 hours of waking up, 5–15 minutes of rest, while maintaining a normal sodium-potassium salt diet, and after ≥4 weeks of discontinuation of medications affecting the renin-angiotensin system. All included patients underwent CT scanning before adrenalectomy. Lateralization of aldosterone overproduction was determined solely based on contrast-enhanced CT findings. Patients with biochemically confirmed PA and preoperative CT findings demonstrating a unilateral adrenal nodule or unilateral morphological abnormality suggestive of an aldosteronoma, with no significant contralateral abnormalities or signs of bilateral hyperplasia, were considered candidates for unilateral adrenalectomy. Patients with preoperative CT findings indicating bilateral nodules, bilateral enlargement, or unequivocal bilateral hyperplasia were excluded. Adrenal vein sampling (AVS) was not routinely performed at our institution during the study period and was not used for surgical decision-making in this cohort, due to its technical complexity and limited real-world availability in our practice setting. Histopathological analysis of surgical specimens documented subtypes. Surgical outcomes were assessed at discharge and at 1, 3, 6, and 12 months postoperatively.

Observational indicators and definitions

Patients were monitored for postoperative blood pressure, postoperative serum potassium, postoperative plasma ARR, postoperative oral antihypertensive medication use, 30-day postoperative complications and rehospitalization rate. The PASO criteria (2) were adopted to define outcomes: (I) CCS was defined as normal blood pressure without antihypertensive medication; (II) clinical partial success (CPS) was defined as reduced blood pressure or reduced antihypertensive dosage while maintaining normotension; (III) nonsuccess (NS) was defined as unchanged or increased antihypertensive dosage without blood pressure improvement. The follow-up period was 3–12 months, with a median of 9 months. Follow-up included outpatient assessment of adrenal hormones and electrolytes, as well as adrenal CT to evaluate surgical site healing. The overall clinical success rate was calculated as: (number of CPS cases + number of CCS cases)/total number of cases × 100%.

Statistical analysis

SPSS 23.0 statistical software was used to analyze and process the data. Mean ± standard deviation was used to describe the data that conformed to a normal distribution and two independent samples t-test was used for comparison between groups. Data that did not conform to normal distribution were expressed as interquartile range (IQR), and comparisons between groups were made using the Mann-Whitney U test. Count data were expressed as examples (%), and comparisons between groups were made using the χ² test. Independent predictors of complete postoperative blood pressure remission were analyzed using univariate and multivariate logistic regression. P value <0.05 was considered statistically significant.

Results

General information

Between January 2018 and January 2023, a total of 226 patients underwent adrenalectomy due to UPA in our hospital. Excluding patients lost to follow-up and incomplete clinical data, a total of 206 patients were included. The general information and baseline data of the patients are shown in Table 1. The patients were 107 (51.9%) males and 99 (48.1%) females, aged 48 (IQR, 37–57) years old, BMI of 25.48±3.53 kg/m², maximum tumor diameter of 1.97 (IQR, 1.29–2.9) cm, 117 (56.8%) on the left side and 89 (43.2%) on the right side. There were 181 (87.9%) cases via the retroperitoneal approach and 25 (12.1%) cases of the robot-assisted retroperitoneal approach.

According to the 2017 Lancet Postoperative Outcome Criteria for Primary Aldosteronism (2) and the 2020 edition of the Expert Consensus on Primary Aldosteronism Diagnosis and Treatment of the Endocrine Group of the Chinese Medical Association, the patients were in CCS in 106 cases (51.46%), CPS in 71 cases (34.47%), and NS in 29 cases (14.08%) after the surgery. There were no rehospitalization cases. The overall clinical remission rate was 85.93%. Biochemical outcomes were not included in the study because confirmatory experiments were not routinely reviewed after surgery.

Difference between groups in CCS and incomplete clinical success (ICS) (including CPS + NS)

There were statistical differences between the two groups in pathological type, BMI, duration of hypertension, preoperative systolic blood pressure, preoperative diastolic blood pressure, and preoperative potassium (P<0.05), whereas there were no statistical differences in gender, age, tumor location, maximum diameter of tumor, surgical method, and preoperative ARR (Table 2).

Preoperative predictors of ICS

Univariate logistic regression analysis showed that pathologic type of unilateral adrenal hyperplasia (UAH), longer duration of hypertension, higher BMI, preoperative systolic and diastolic blood pressure, and lower preoperative potassium were associated with Partial remission (P<0.05). Multivariate logistic regression analysis showed that UAH [odds ratio (OR) =3.920, P=0.04], high BMI (OR =1.486, P<0.001), duration of hypertension (OR =1.156, P<0.001), and preoperative systolic blood pressure (OR =1.280, P<0.001) were independent risk factors for ICS (Table 3).

Discussion

An international multicenter cohort study defined the outcomes and follow-up criteria after adrenalectomy for UPA in 2017 (2). The PASO evaluation criteria were recommended in the 2020 expert consensus of the Chinese Society of Endocrinology of the Chinese Medical Association on the diagnosis and treatment of PA. The results of the PASO study showed that 37% of the patients were CCS (2). The results of several systematic evaluations and meta-analyses showed CCS rates of 42%, 50%, and 52% (3-5). In this study, the CCS rate was 51.46%, which is similar to previous studies (3-5). The CCS rate varied greatly between studies.

Multi-institutional studies (6-8) have demonstrated that lower BMI tends to be associated with CCS after adrenalectomy in UPA, which is consistent with our findings. However, few reports have elucidated the mechanism behind its occurrence. We hypothesize that this may be related to patients with obesity having higher aldosterone levels. Expression of the mineralocorticoid receptor is significantly increased in adipose tissues of patients with obesity, which has been implicated in the progression of the metabolic syndrome (9). In addition, there are mechanisms regulating aldosterone by adipose tissues (10). Adipocytes regulate aldosterone secretion through activation of the renin-angiotensin-aldosterone system (RAAS) or the production of salocorticotropin-releasing factor (STRF) and adipose-derived factors (leptin, lipocalin, and CTRP1). Among these, aldosterone production is dependent on increased leptin signaling. Lipocalin regulates aldosterone secretion by acting on lipocalin receptor subtypes in the adrenal cortex and is protective against obesity-induced complications (11). New studies deserve to be conducted to elucidate the role of aldosterone in relation to adipocytes.

Ahn et al. revealed that histopathologic subtypes of PA are associated with clinical phenotype and postoperative outcome (12). In our study, the pathology type after UPA was statistically different in predicting postoperative CCS. Patients with aldosterone adenomas were more likely to achieve a CCS. Saadi et al. found the same result (13). Christophe et al. reported that adrenal hyperplasia was more likely to have persistent postoperative hypertension (14). However, the mechanism of its unremitting postoperative hypertension is unclear.

Our group found that the degree of preoperative hypertension and the duration of hypertension in UPA patients were independent predictors of postoperative CCS, which was similar to the results of domestic and foreign clinical studies (13). The results of a Meta-analysis based on data from SOPRANO showed that hypertension duration was negatively associated with CCS (8). A machine learning model study reported that hypertension duration was the feature most associated with CCS (7). The persistence of hypertension due to prolonged aldosterone overproduction may have deleterious and irreversible effects on the cardiovascular system. The mechanistic relationship between hypertension duration and clinical outcomes needs to be further investigated. Long duration of hypertension or a higher blood pressure threshold can cause irreversible damage to the vasculature. The currently recognized theories include endothelial cell dysfunction, inflammatory response, and oxidative stress (11,15). Hypertensive patients with chronic hyperaldosteronism who require multiple medicines to control exhibit an increased chance of vascular remodeling, including increased intima-media thickness and arterial stiffness (16).

Burrello et al. found that the lower the preoperative potassium level, the higher the clinical success rate (17). They interpreted that the degree of hypokalemia reflected the severity of aldosteronism. We found that preoperative hypokalemia was associated with postoperative CCS. Multivariate logistic regression analysis found no statistical difference between them, which may be related to our insufficient sample size. We will continue to collect more cases to expand the sample size and reduce the influence of confounding factors. Manosroi et al. have demonstrated that advanced age (beyond 60 years) is also an independent risk factor for ICS (6). It may be due to primary hypertension being more common in older patients (18). The poorer vascular conditions result in a higher probability of persistent postoperative hypertension (19). There was no significant statistical difference between age and the degree of CCS in this study. Some successful cases often show a delayed clinical normalization trajectory that differs from complete and non-successful cases, especially when partial adrenalectomy is performed. Our team’s ongoing research formally describes these differentiated recovery patterns.

Our results suggest that BMI and histology are independent influencing factors for postoperative clinical remission. Critically, these factors extend beyond predictive value to directly inform surgical strategy. Elevated BMI is recognized as an independent predictor of intraoperative complications, as evidenced by recent large-scale institutional databases (20,21). Nevertheless, contemporary multicenter analyses specifically examining posterior retroperitoneoscopic adrenalectomy demonstrate that obesity should not preclude minimally invasive approaches. These studies confirm comparable perioperative morbidity and mortality rates between obese and non-obese cohorts, despite longer operative times. Functional outcomes further justify surgical intervention across BMI strata (20-22). The multinational SOPRANO meta-analysis reported near-universal biochemical success following adrenalectomy for PA, though higher BMI inversely correlated with complete clinical cure rates (8). An additional cohort study observed more pronounced reductions in antihypertensive medication requirements among obese patients postoperatively (23). These findings collectively support individualized surgical planning. For well-localized aldosterone-producing adenomas, minimally invasive partial adrenalectomy achieves clinical control equivalent to total resection while preserving adrenal function. This approach is particularly advantageous in unilateral disease without bilateral predisposition, as substantiated by high-volume institutional series. Surgical decision-making should therefore integrate tumor functionality, histopathological characteristics, BMI-adjusted risk stratification, and institutional expertise in minimally invasive techniques.

There are also limitations to this study. This is a single-center retrospective analysis, and the differences in biochemical outcomes were not analyzed due to the fact that confirmatory tests were not routinely performed in the postoperative period. A multicenter clinical study will be conducted in the future to expand the sample size and further research will be conducted to provide new protocols for the follow-up of UPA patients after MIA. This study is limited by the absence of routine adrenal venous sampling for lateralization, relying instead on biochemical profiling and CT findings. Future studies incorporating AVS would strengthen diagnostic certainty. In addition, our findings thus represent outcomes achievable when selecting surgery via biochemical profiling and CT criteria in settings where AVS is unavailable. While the PASO criteria provide standardized clinical outcomes, our study did not incorporate biochemical remission data. This omission limits direct comparison with emerging multidimensional frameworks that integrate biochemical and clinical endpoints. Our prioritization of PASO aimed to align with widely adopted surgical benchmarks. However, future studies should adopt composite metrics to better capture the complexity of post-adrenalectomy outcomes. The median follow-up duration was insufficient to comprehensively evaluate the long-term efficacy endpoints of the surgery. Although this timeframe met the PASO consensus criteria for monitoring early response, it failed to adequately capture the dynamic processes of blood pressure normalization and medication load changes, particularly for partial response patients whose clinical trajectories may span over 24 months. This limitation stems from inherent fragmentation in retrospective designs and issues with patient dropout.

Conclusions

In this study, we retrospectively analyzed the clinical data of 206 patients and concluded that UAH, high BMI and preoperative systolic blood pressure, and long duration of hypertension were independent risk factors for postoperative ICS in patients with UPA. It is beneficial for the surgical team to assess the condition of patients and predict efficacy to develop a better postoperative treatment and follow-up program.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-176/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-176/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-176/prf

Funding: Natural Science Research in Shanxi Province (No. 202203021211072) financially supported this research.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-176/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Shanxi Bethune Hospital (No. SBQLL-2019-092) and informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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