Objective: Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally. Methods: Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and postoperative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in the SPARTACUS trial who underwent AVS. Previously published prediction models were also tested in our cohorts. Results: Backward stepwise logistic regression analysis yielded a final tool using baseline aldosterone-to-lowest-potassium ratio (APR, ng/dl/mmol/l), with an area under receiver-operating characteristic curve of 0.80 (95% CI 0.70–0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR <5) and probability of unilateral disease was 91.4% (with APR >15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR <5), and probability for unilateral was 91.7% (with APR >15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA. Conclusion: The novel aldosterone-to-lowest-potassium ratio is a convenient score to guide clinicians and patients of various ethnicities on the probability of primary aldosteronism subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.

ContextStudies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery.ObjectiveTo compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA.DesignRetrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019.Patients154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy.MeasurementsPrimary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control.ResultsCardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32–2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0–2.0) versus 2.6 (IQR 0.8–4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery.ConclusionIn patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.

Background: In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy versus mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment. Design and Methods: A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to Dec 18, 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). Results: A total of 9 studies with 8,473 adult patients with PA (≥18 years) were enrolled. Lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 [95% CI, 0.38-0.56], P < 0.001). We found lower incidence of all-cause mortality (OR: 0.33 [95% CI, 0.15-0.73], P = 0.006) and MACE (OR: 0.55, [95% CI, 0.40-0.74], P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 [95% CI, 0.15-0.75], P = 0.008), arrhythmias (OR: 0.46 [95% CI, 0.27-0.81], P = 0.007), and congestive heart failure (OR: 0.52 [95% CI, 0.33-0.81], P = 0.004) were also lower in adrenalectomy group. The meta regression showed patient’s age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 [95% CI, 1.005-1.169], P = 0.036). TSA demonstrated that the accrued sample size as well as effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. Conclusions: In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.