Biochemical and clinical remission after adrenalectomy in patients with primary aldosteronism: a retrospective two-center study

Introduction

Hypertension is frequent in the adult general population and can lead to potential severe long-term complications. Primary hyperaldosteronism (PHA), affects around 11% of patients with hypertension (1). Its prevalence increases with the severity of hypertension, affecting up to 29.8% of patients with resistant hypertension (2). Accordingly, the 2016 guidelines of the Endocrine Society recommend screening for PHA in all patients with the following conditions: blood pressure (BP) >140/90 mmHg despite 3 conventional antihypertensive drugs (including a diuretic), or controlled BP (<140/90 mmHg) on ≥4 drugs, hypertension and hypokalemia, hypertension and adrenal incidentaloma, hypertension and sleep apnea, hypertension and family history of early onset hypertension or cerebrovascular accident at a young age (<40 years) and/or first degree relatives with PHA (3). Recent European Society of Hypertension (ESH) guidelines even recommend screening all patients with hypertension prior to treatment initiation (4). PHA should be screened for and treated given that, in addition to its prevalence, it has pro-inflammatory and profibrotic effects on the heart and vessel walls that result in significantly higher cardiovascular morbidity than in cases of essential hypertension (5-7).

While idiopathic bilateral hyperplasia [idiopathic hyper aldosteronism (IHA)] is the source of hypersecretion in most cases (50–60%), unilateral aldosterone producing adenoma (APA) is responsible for the disease in about 35–40% of cases (3). Unilateral hyperplasia has also been described and could be more frequent than previously believed (8). Once PHA is diagnosed based on increased aldosterone-to-renin ratio (ARR) and positive confirmation tests, adrenal imaging should be performed. If an adrenal nodule is found in a patient with PHA, the most frequent etiology is an APA, but the possibility of adrenal hyperplasia (IHA) or a non-secreting incidentaloma needs to be excluded (5). The use of adrenal venous sampling (AVS) is thus crucial to determine the lateralization of aldosterone secretion excess and avoid unnecessary adrenalectomy or removal of the wrong adrenal gland, which has been reported in up to one third of cases in some series (9).

According to the 2016 guidelines of the Endocrine Society (3), in patients younger than 35-40 years presenting with PHA, hypokalemia and a clear unilateral adrenal adenoma, surgery without AVS can be considered. However, recent studies have questioned the reliability of imaging alone in identifying unilateral disease (10,11).

In patients diagnosed with unilateral PHA, the latest guidelines recommend laparoscopic adrenalectomy, as these patients are more likely to require fewer medications at lower defined daily doses to achieve normalization of BP and potassium levels (3,12-15).

Expected benefits from surgery include the prevention of adverse events due to hyperaldosteronism, a long-term cure with reversal of cardiovascular damage, reduction of antihypertensive medications and an improvement in quality of life. Although most patients benefit from a significant decrease in aldosterone levels and BP, only approximately 50% achieve complete resolution of hypertension without the need for antihypertensive medications after surgery (16). This may be explained by the presence of underlying essential hypertension in many of these patients.

Although adrenalectomy is the recommended treatment for unilateral PHA, studies still report significant variability in the proportion of patients who achieve full remission (17-19). This is partly due to the lack of standardized criteria for defining clinical and biochemical response. To address this, the Primary Aldosteronism Surgical Outcome (PASO) study established international consensus definitions for complete, partial, and absent success after adrenalectomy (17). According to PASO, complete clinical success is defined as “normal blood pressure (<140/90 mmHg) without the use of any antihypertensive medications”, and complete biochemical success as “correction of hypokalemia and normalization of ARR”. However, ARR interpretation has limitations, especially in patients taking β-blockers or in the immediate postoperative period, when renin remains suppressed, potentially making postoperative aldosterone levels a more reliable indicator of biochemical response (20,21).

The aim of this study was to analyze pre- and post-operative serum aldosterone levels and to assess biochemical response after unilateral adrenalectomy for PHA, as well as to evaluate clinical outcomes according to this definition.

In addition, imaging and AVS findings were analyzed to assess their concordance and role in guiding surgical decision-making. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0087/rc).

Methods

This is a retrospective, multicentric observational cohort study including 82 consecutive adult patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2006 and December 2017 at two tertiary academic centers in Switzerland (University Hospital of Geneva and University Hospital of Lausanne). These two centers were selected because of their established collaboration for adrenal vein sampling (AVS), systematically performed at Lausanne University Hospital for both institutions. Patient identification was performed through surgical records and electronic medical files. Both centers perform more than 20 adrenalectomies per year. All adult patients diagnosed with primary aldosteronism and treated surgically were included. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Cantonal Research Ethics Commission of Geneva (CCER) and the Cantonal Research Ethics Commission of Vaud (CER-VD) (No. 2018-00975), and individual consent for this retrospective analysis was waived.

Variables collected—definitions

Data were collected from reports of outpatient clinic, imaging [computed tomography (CT), magnetic resonance imaging (MRI)], AVS, hospital length of stay, surgical procedure (laparoscopic, open, conversion and duration) and histopathology. Histological classification was based on routine pathological reports and did not systematically distinguish between zona glomerulosa and zona fasciculata hyperplasia. Laboratory values included plasma aldosterone concentration (PAC), serum potassium levels, and renin when available. The number of antihypertensive drugs taken by patients were analyzed pre- and postoperatively. Postoperative information included hospital length of stay and complications using the Clavien-Dindo classification (22).

Biochemical response was defined as the normalization or postoperative decrease of serum aldosterone. All patients had a pathological ARR preoperatively, indicating autonomous aldosterone secretion, even in those with aldosterone values within the normal laboratory range. This explains why some patients presented aldosterone levels within the normal range despite confirmed PHA. Because renin remains physiologically suppressed in the early postoperative period and renin measurements were only available immediately after surgery, ARR could not be reliably calculated.

Therefore, postoperative aldosterone levels alone were used as a pragmatic surrogate to assess biochemical response. This definition reflects early biochemical response rather than definitive long-term biochemical response, given the lack of standardized postoperative renin measurements and follow-up. This pragmatic approach is consistent with the rationale of the PASO consensus, which acknowledges that, in the immediate postoperative period, aldosterone levels may serve as a more reliable indicator of biochemical improvement than the ARR, especially when renin remains suppressed (17,23).

To standardize aldosterone measurements across centers, values were expressed as a ratio to the upper limit of the corresponding normal range. Aldosterone was measured using liquid chromatography tandem mass spectrometry (LC/MS/MS) and reported in pmol/L, with reference values 147.8–1,154.6 pmol/L. A binary variable was then created to encode postoperative biochemical outcome: values classified as normal, or showing a reduction compared to preoperative levels, were coded as cure, whereas persistently elevated values were coded as non-cure.

Clinical cure was defined as a reduction in the number of antihypertensive medications and/or cessation of potassium supplementation, regardless of the number of drugs stopped.

Biochemical response was assessed based on postoperative aldosterone levels. Therefore, postoperative aldosterone levels alone were used as a pragmatic surrogate to assess biochemical response, reflecting the retrospective design and the lack of standardized postoperative renin measurements. Postoperative biochemical measurements were obtained during the early postoperative period, typically within the hospital stay (postoperative days 1–3), although timing was not standardized.

This pragmatic definition differs from PASO consensus criteria and may limit direct comparability with studies using standardized definitions.

Although some patients only discontinued one medication, most often a mineralocorticoid receptor antagonist, this pragmatic definition reflects real-life management and is consistent with previous retrospective studies (24,25). Due to the retrospective design, standardized BP measurements were not consistently available; therefore, the number of antihypertensive medications was used as a surrogate marker of clinical outcome.

In order to determine the concordance between imaging and lateralization study, we compared the side of adrenal pathology on CT or MRI with the result of AVS.

Additionally, the correlation between the adrenal gland anatomy on imaging (nodule or adrenal thickening) and the definitive pathology result (solitary adenoma, multiple adenomas, multinodular or micronodular hyperplasia) was analyzed.

Statistical analysis

Parametric and nonparametric data were analyzed using a t-test on the equality of means. Data are presented as number of observation and percentages for categorical variables and median with interquartile range for continuous ones or mean when appropriate. Linear regression was used for the mentioned variables. For multivariate analyses, we included clinically relevant covariates based on known factors influencing BP and aldosterone levels, namely age, sex, body mass index (BMI), and duration of hypertension (3).

A P value of <0.05 was considered statistically significant. Stata Statistical Software: Release 15 (StataCorp. 2017, College Station, TX, USA) was used to perform univariate and multivariate analyses.

Results

Eighty-two patients (51 male, 62.2%) who underwent adrenalectomy for primary aldosteronism between January 1, 2006 and December 31, 2017, were included in the study. This cohort represents all patients operated during this period, and no patient was excluded from the analysis.

Patient baseline characteristics, including gender, American Society of Anesthesiologist (ASA) score, BMI, number of antihypertensive medications, potassium supplementation, imaging and AVS findings are detailed in Table 1.

Mean age at the time of operation was 49.6 years [standard deviation (SD) 10.6].

All patients underwent preoperative adrenal imaging (CT or MRI), and solitary unilateral nodules, with a median diameter of 1.4 cm (range, 1.1–1.8 cm), were identified in 76.5% of cases (n=62). Other findings included adrenal thickening in 4.9% of cases (n=4), found to be bilateral in half of them. Three patients were found to have multiple nodules, located in the same gland in two cases.

Normal adrenal gland anatomy was described in 14.8% of imaging reports (n=12). Most adrenal lesions (n=43) were situated on the left side (53.1%) and 28.4% localized to the right side. Bilateral abnormalities were found in 3 patients (3.7%) and bilateral normal adrenal gland anatomy was found in 12 cases (14.8%).

The median preoperative serum aldosterone level could not be precisely determined in ng/L due to data heterogeneity, but the mean aldosterone-to-normal ratio was 1.65. Hypokalemia was present in approximately 36.6% of cases, as indicated by the need for potassium supplementation. Patients were on a median of 3 antihypertensive drugs preoperatively.

AVS was carried out in 87.8% of cases (n=72). Among patients with a clearly lateralized unilateral lesion on CT or MRI (n=67), AVS results were concordant with imaging findings in all cases (Table 2). Concordance between imaging and AVS was therefore observed only in patients with a clearly lateralized unilateral lesion on imaging.

Imaging alone cannot reliably distinguish functional adenomas from non-functional nodules. In our cohort, discrepancies between imaging and histological findings likely reflect limitations in imaging resolution and the presence of small or non-visible lesions, particularly for nodules below 1–1.5 cm.

Importantly, in 15 patients with either normal adrenal glands or bilateral lesions on imaging, AVS findings were fundamental in determining the side of adrenalectomy accounting for 20% of the total AVS procedures. In these cases, AVS played a decisive role in guiding surgical management. In 10 patients, AVS was not performed because of the presence of a unilateral lesion on imaging. This reflects local practice during the study period (2006–2017), prior to the 2016 Endocrine Society guidelines recommending systematic AVS in patients over 35 years of age with suspected primary aldosteronism (3). Postoperative aldosterone measurements were available for 7 of these 10 patients, and all 7 showed a postoperative decrease compared to preoperative levels.

Surgery

In our study period, 82 laparoscopic transabdominal adrenalectomies were performed for PHA, 30 in Geneva and 52 in Lausanne. Two conversions to laparotomy were necessary due to technical difficulties caused by excessive retroperitoneal fat tissue occurring in one center in 2014 and 2017.

The mean operating time was 112.5 minutes and postoperative complications occurred in 14.6% of cases (n=12/82). Most patients (83.3%) presented Clavien-Dindo grades I and II complications, including four cases of urinary retention, one urinary infection, one ileus, one acute renal failure and one diabetic decompensation. One patient developed severe pneumonia with septic shock and another required reoperation due to spleen malposition after left adrenalectomy. The median hospital length of stay was 4 days (range, 3–6 days).

Histology

Solitary adenomas were confirmed by pathologists in 75.6% of cases, and hyperplasia was described in 24.3% of adrenal gland specimens overall. Among the patients with a unilateral adrenal lesion identified on imaging, 13 (15.9%) were found at histological analysis to have hyperplastic changes without a true adenoma. These hyperplastic forms were further categorized as follows: three cases showed diffuse hyperplasia without any nodule, two cases presented with micronodular hyperplasia, five cases exhibited micronodular hyperplasia with one dominant nodule, and three cases showed multinodular hyperplasia with one dominant nodule.

In these 13 cases, adrenal vein sampling (AVS) results were concordant with imaging findings, which supported the indication for unilateral adrenalectomy despite the final diagnosis of hyperplasia. This discrepancy highlights the limitations of imaging alone in differentiating between aldosterone-producing adenomas and hyperplastic changes.

BP and hypokaliemia: clinical cure?

After adrenalectomy, the mean number of antihypertensive medications decreased significantly from 2.92 to 0.92 (P<0.001). Before surgery, 44 patients (53.6%) were taking at least three antihypertensive drugs, and 19 of them (43.2%) required four or five medications; among these 19 patients, 14 (73.7%) were treated with mineralocorticoid receptor antagonists (Figure 1). After surgery, only 4 of these 19 patients (21.1%) still required four medications. Overall, 44 patients (53.6%) were able to completely discontinue antihypertensive therapy.

Figure 1 Distribution of the number of antihypertensive medications before and after adrenal surgery. The bar chart shows the percentage of patients according to the number of antihypertensive drugs required preoperatively (blue) and postoperatively (red). A marked reduction in antihypertensive treatment is observed after surgery, with 53.6% of patients requiring no antihypertensive medication postoperatively. Artificial intelligence-assisted tools were used for figure preparation.

Figure 2 illustrates the distribution of the extent of antihypertensive medication reduction following adrenal surgery. Overall, a reduction in antihypertensive treatment was observed in 85.7% of patients, including the 53.6% who were able to discontinue antihypertensive therapy completely.

Figure 2 Distribution of the reduction in antihypertensive medication burden following adrenal surgery. The figure shows the proportion of patients according to the number of antihypertensive drugs withdrawn postoperatively. Complete withdrawal of antihypertensive treatment was achieved in 12.5% of patients. Artificial intelligence-assisted tools were used for figure preparation.

Regarding the use of aldosterone-antagonists before surgery, 53.7% of patients required spironolactone and 20.7% eplerenone. The mean quantity of both aldosterone-antagonists in the cohort was significantly reduced after surgery, with postoperative spironolactone and eplerenone down to 2.4% (P<0.001) and 2.4% (P<0.001), respectively.

For potassium supplementation, the mean daily frequency of administration decreased significantly after adrenalectomy (0.72 vs. 0.11; P<0.001) and in 93.6% of cases, serum potassium values returned to normal without the need for treatment (Figure 3).

Figure 3 Potassium supplementation before and after adrenal surgery. The proportion of patients requiring potassium supplementation markedly decreased after adrenalectomy, with normalization of serum potassium levels without treatment in 93.6% of cases. Artificial intelligence-assisted tools were used for figure preparation.

Complete clinical success, defined as discontinuation of all antihypertensive medications, was achieved in 53.6% of patients.

Aldosterone levels: biochemical response?

We analyzed serum aldosterone levels in supine patients. Due to the retrospective design, postoperative biochemical data were incomplete, with paired aldosterone measurements available in 43 patients (52.4%) as summarized in Table 3. Among them, 25 patients had elevated aldosterone levels preoperatively, and all (100%) showed normalization after surgery. The remaining 18 patients had aldosterone values within the normal range before surgery; however, all of them had a pathological ARR. After surgery, 17 of these 18 patients (94.4%) maintained normal aldosterone levels, while only 1 patient (5.6%) showed a postoperative increase. Overall, postoperative aldosterone levels were within the normal range in 97.7% of cases, reflecting effective suppression of aldosterone hypersecretion following adrenalectomy.

However, due to the retrospective nature of the study and the lack of standardized ARR values across centers, biochemical remission could not be formally defined according to current guidelines. Therefore, postoperative aldosterone levels were used pragmatically as a surrogate marker of biochemical outcome.

After adrenalectomy, the ratio of serum aldosterone level to the upper limits of normal was significantly lower (P<0.001) (Table 4). A multivariate analysis taking BMI and ASA into account also showed a significant reduction of this ratio after surgery (P<0.001). Figure 4A illustrates individual pre- and postoperative changes in the aldosterone-to-upper-limit-of-normal ratio, highlighting the marked decrease observed in the vast majority of patients after adrenal surgery. Among patients with preoperative aldosterone levels within the normal range (defined as an aldosterone-to-upper-limit-of normal ratio ≤1; n=11), most demonstrated a further postoperative decrease (Figure 4B). One patient showed a slight increase above the upper limit of normal.

Figure 4 Pre- and postoperative aldosterone-to-upper-limit-of-normal ratios after adrenalectomy. (A) Pre- and postoperative aldosterone levels expressed as a ratio to the ULN. Each line represents an individual patient. A decrease in ratio indicates a postoperative reduction in aldosterone. A ratio ≤1 corresponds to aldosterone levels within the normal range. The plot shows that the majority of patients experienced a postoperative decline, and all postoperative values were within the normal range. Artificial intelligence assisted-tools were used for figure preparation. (B) Pre- and postoperative aldosterone levels (ratio to ULN) in patients with normal preoperative values. Analysis restricted to patients with preoperative aldosterone levels within the normal range (defined as an aldosterone-to-upper-limit-of-normal ratio ≤1), allowing better visualization of postoperative changes within the normal range. Most patients demonstrate a postoperative decrease, while one patient shows a slight increase above the upper limit of normal. Artificial intelligence-assisted tools were used for figure preparation. ULN, upper limit of normal.

Discussion

This study’s findings confirm that aldosterone levels were in the normal range for the majority of patients (97.7%) after adrenalectomy for PHA and that more than half of the patients were able to completely discontinue antihypertensive treatment.

Our primary endpoint was to evaluate the biochemical response after surgery, pragmatically defined as the normalization of aldosterone levels postoperatively. In patients with elevated preoperative aldosterone, cure was considered as normalization of levels after surgery.

Until recently, the use of different diagnostic techniques and cutoffs, as well as the vague definitions of what constitutes cure and how to report changes in biochemistry, have posed significant challenges in determining the outcomes after adrenalectomy for PHA. As mentioned above, the PASO study (17) established definitions for biochemical and clinical success that are divided into three categories: complete, partial and absent success. A decrease in baseline plasma aldosterone level is one of the criteria for the evaluation of biochemical success. Even if not fully curative, the reduction of aldosterone in the blood stream leads to the reduction of its detrimental effects on heart, kidney and vessels.

Recent studies have emphasized the importance of standardized criteria such as PASO and the need for long-term follow-up in the evaluation of surgical outcomes for unilateral PA (26).

Indeed, hypertensive patients have an elevated risk of developing cardiovascular, cerebrovascular and renal diseases due to aldosterone excess when compared to patients with primary hypertension (23,27,28). This is due to the profibrotic and pro-inflammatory effect of aldosterone on the arterial wall, myocardial and renal tissue, which leads to fibrotic changes. Elimination of excessive aldosterone production is therefore primordial in treatment of PHA, even if hypertension can persist after surgical removal of the pathologic adrenal gland.

According to our predefined pragmatic definition, 53.6% of patients discontinued all antihypertensive therapy (complete clinical success by our criteria), and 85.7% experienced a partial clinical response with a reduced medication burden. This result is in line with published rates, with complete clinical success achieved in less than 50% of cases (29).

Despite complete clinical success being achieved in only about half of patients, biochemical success was observed in the vast majority of cases, confirming the effectiveness of adrenalectomy in suppressing autonomous aldosterone secretion. The number of antihypertensive drugs was reduced for most patients (85.7%), and the benefits of surgically eliminating excess aldosterone to prevent long-term complications should always be considered when weighing treatment options, even if complete clinical success is not guaranteed after adrenalectomy.

The complication rate reported in our study is 14.6%, which is within the range reported in the literature (2–14%) (18,30). Most complications (83.3%) were low-grade (Clavien Dindo I–II).

Another important aspect is localizing the side of hypersecretion and being aware that older individuals (>35 years old) are more likely to have non-functioning adenomas. Microadenomas (less than 10 mm) are rarely detected on CT imaging and normal adrenal gland anatomy is often described by radiologists. In our study, 14.8% of patients were described to have adrenal glands with normal anatomy yet final histology revealed that they actually had pathological changes (adenomas, hyperplasia and micronodular changes). Lateralization study remains integral part of the workup of PHA and the 2016 Endocrine Society guidelines (3) recommend AVS as gold standard for determining laterality in patients with confirmed PHA. However, AVS remains invasive procedure and is not available in every center. In our study, patients were referred to one of the two academic centers where an interventional radiologist performed the sampling and a dedicated nephrologist analyzed the results.

Importantly, among patients with a clearly lateralizing unilateral adrenal lesion on CT of MRI, AVS did not change the surgical side in any case, regardless of patient age. In this subgroup, cross-sectional imaging alone was sufficient to guide surgical management, and AVS served only as a confirmatory test rather than a decision-altering tool. AVS impacted management exclusively in cases with non-lateralizing or discordant imaging findings. This selection strategy may explain the absence of discordant imaging and AVS findings and represents a potential selection bias. Recent guidelines from the American Association of Endocrine Surgeons (AAES) continue to support the use of AVS but acknowledge that it may be safely omitted in selected patients, particularly those under 35 years of age with marked biochemical abnormalities and a clear unilateral adrenal lesion on imaging (15).

In the future, this method will likely be replaced or complemented by functional molecular imaging approaches like 11C-metomidate positron emission tomography (PET)/CT (31), iodomethyl-19-norcholesterol scan (32) or 68Ga-pentixafor PET/CT, which targets CXCR4 expression in aldosterone-producing-adenomas (33). More recently, 18F-AIF-NOTA-pentixafor PET/CT has also demonstrated promising results in lateralization, with a prospective comparative study confirming its added value over AVS in selected patients (34).

Our study also comes with a number of limitations, namely its retrospective design and the lack of homogeneity in the management of patients. This was caused, in part, by the long interval of over 10 years between the first and the last operation recorded and the lack of standardization in diagnostic definitions at the time of the study. The analysis of aldosterone levels was limited by the heterogeneity of laboratory results, where different units and a different normal range were used. We thus used the ratio of aldosterone levels to normal aldosterone values to determine aldosterone reduction.

Furthermore, because of the retrospective nature of our study and missing variables, only 43 patients (52.4%) had both pre- and postoperative aldosterone values available for direct comparison.

In addition, the timing of postoperative data collection was not standardized, and follow-up was most often limited to the hospital stay. Given the short half-life of aldosterone (approximately 20 minutes), early postoperative normalization may reflect acute adrenal removal rather than sustained biochemical cure, thus limiting the assessment of long-term outcomes.

Long-term biochemical follow-up was not consistently available in our cohort, and our analysis therefore focuses on early postoperative biochemical response.

A substantial proportion of patients had aldosterone levels within the normal range preoperatively despite confirmed primary aldosteronism based on ARR and/or AVS. This should be taken into account when interpreting postoperative normalization rates, as biochemical response in these patients reflects correction of inappropriate aldosterone secretion rather than normalization of an overtly elevated baseline value. In this context, the isolated postoperative increase observed in one patient may be related to biological variability, differences in sampling conditions (e.g., posture, volume status), or interassay variability, and does not appear to reflect true persistent hyperaldosteronism.

In addition, perioperative factors such as intravenous saline infusion may transiently suppress aldosterone levels, potentially leading to an overestimation of early biochemical response. Standardized postoperative renin measurements were not available, although some authors recommend monitoring renin to better assess biochemical outcomes, particularly when renin remains suppressed (17,23).

Clinical and biochemical outcomes were not systematically paired at the individual patient level, which limits direct comparison between these endpoints.

We did not perform a formal comparison of outcomes between patients with histologically confirmed adenoma and those with hyperplasia due to limited subgroup sizes.

In patients without histologically confirmed adenoma, the possibility of bilateral disease cannot be completely excluded, although surgical indication was based on AVS demonstrating unilateral aldosterone excess.

Overall, our definition of biochemical outcome should be interpreted with caution and reflects early biochemical response rather than definitive long-term cure. These findings should be interpreted in the context of historical practice prior to standardized criteria.

Although this study is based on data collected over a decade ago, it provides a valuable historical reference for the management of unilateral PHA prior to the widespread adoption of standardized criteria.

Conclusions

Our study, conducted in two academic centers in Switzerland, found that the wide majority of patients with PHA due to a unilateral adrenal gland nodule had normal aldosterone levels after adrenalectomy and were considered biochemically cured. These findings are concordant with published results.

Based on our findings, we thus recommend that surgery always be the offered therapy in case of unilateral aldosterone excess production.

For the observed lack of standardization in the pre- and postoperative management of PHA between our two institutions, we recommend following current guidelines (3) to better select and prepare patients who will benefit from surgery. Moreover, postoperative aldosterone and potassium levels can be measured to confirm biochemical response, ideally before the patient’s discharge from the hospital. The clinical cure requires a longer follow-up, although this is rarely done by surgical teams.

These results will provide a benchmark for a forthcoming retrospective analysis using more recent data, which will allow a direct comparison of outcomes before and after the implementation of consensus guidelines such as PASO and AAES.

Such comparison may offer further insight into the impact of standardization on clinical cure rate and biochemical response following adrenalectomy.

In addition, longer follow-up will be essential to fully assess the long-term clinical success of surgical treatment.

Acknowledgments

The authors acknowledge the use of artificial intelligence–assisted tools for language editing and improvement, and for assistance in figure preparation. No AI tools were used for data analysis and scientific interpretation. The abstract of this work was presented at the European Society of Endocrine Surgeons congress and at the Swiss Surgical Congress in 2020. The authors would like to thank Ilaria Di Meglio for her assistance with manuscript formatting and language editing.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0087/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0087/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0087/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0087/coif). F.T. received consulting fees from Medtronic and Getinge (Fluoptics) for topics unrelated to this paper. The other 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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Cantonal Research Ethics Commission of Geneva (CCER) and the Cantonal Research Ethics Commission of Vaud (CER-VD) (No. 2018-00975), and individual consent for this retrospective analysis was waived.

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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