Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism.

Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.

Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study.

OBJECTIVES: The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L-1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA. DESIGN: An international, multi-centre cohort study. METHODS: Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed. RESULTS: A combination of PAC <300 pmol L-1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%-38% of patients with PA to bypass AVS and proceed directly to medical treatment. CONCLUSION: In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L-1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.

Risky business: a single-centre cross-sectional analysis of calculated cardiovascular risk in patients with primary aldosteronism and essential hypertension.

OBJECTIVES: Primary aldosteronism (PA), the most common endocrine cause of hypertension, is associated with a higher risk of cardiovascular disease (CVD) than blood pressure (BP)-matched essential hypertension (EH). We aimed to compare the calculated risks of CVD in patients who had hypertension with PA or EH using CVD risk calculators, hypothesising that they will fail to recognise the increased CVD risk in PA. DESIGN: Cross-sectional analysis. SETTING: An endocrine hypertension service in Victoria, Australia. PARTICIPANTS: Patients who had hypertension without CVD referred for the investigation of hypertension. OUTCOME MEASURES: Calculated 5-year or 10-year CVD risk as predicted by the National Vascular Disease Prevention Alliance (NVDPA) algorithm, Framingham Risk Score, Pooled Cohort Equations and QRISK3. RESULTS: Those with PA (n=128) and EH (n=133), did not differ significantly in their calculated CVD risks with the NVDPA algorithm (moderate-to-high 5-year risk 36/100 vs 45/99, p=0.17); the Framingham Risk Score (median 10-year risk 7.72% (4.43%-12.95%) vs 6.84% (3.85%-10.50%), p=0.14); the Pooled Cohort Equations (median 10-year risk 9.45% (4.36%-15.37%) vs 7.90% (2.09%-14.73%), p=0.07); and QRISK3 (median 10-year risk 11.31% (7.22%-20.29%) vs 12.47% (5.10%-19.93%), p=0.51). Similarities persisted on regression analyses accounting for systolic BP. CONCLUSIONS: CVD risk algorithms do not reflect the increased risk of CVD in patients with PA, and likely underestimate the true risk of CVD among those with PA. Screening for PA, in addition to using the CVD risk algorithm in patients who had hypertension, may facilitate the targeted treatment of PA and minimisation of cardiovascular risk in affected individuals.

A representation-independent electronic charge density database for crystalline materials.

In addition to being the core quantity in density-functional theory, the charge density can be used in many tertiary analyses in materials sciences from bonding to assigning charge to specific atoms. The charge density is data-rich since it contains information about all the electrons in the system. With the increasing prevalence of machine-learning tools in materials sciences, a data-rich object like the charge density can be utilized in a wide range of applications. The database presented here provides a modern and user-friendly interface for a large and continuously updated collection of charge densities as part of the Materials Project. In addition to the charge density data, we provide the theory and code for changing the representation of the charge density which should enable more advanced machine-learning studies for the broader community.

Aldosterone, Renin, and Aldosterone-to-Renin Ratio Variability in Screening for Primary Aldosteronism.

CONTEXT: The plasma aldosterone concentration (PAC), renin, and aldosterone-to-renin ratio (ARR) are used to screen for primary aldosteronism (PA). Substantial intra-individual variability of PAC and ARR using plasma renin activity in the context of usual antihypertensive therapy has been described, but there is no data on ARR variability calculated using direct renin concentration (DRC). OBJECTIVE: To describe the intra-individual variability of PAC, DRC, and ARR in the absence of interfering medications in patients with and without PA. DESIGN: Retrospective cohort study. PATIENTS: Hypertensive patients referred for investigation of PA, with at least 2 ARR measurements while off interfering medications. SETTING: Endocrine hypertension service of a tertiary center, from May 2017 to July 2021. MAIN OUTCOME MEASURES: PAC, DRC, and ARR variability was calculated as coefficient of variation (CV) and percent difference (PD). RESULTS: Analysis of 223 patients (55% female, median age 52 years), including 162 with confirmed PA, demonstrated high variability with a sample CV of 22-25% in the PAC and sample CV of 41% to 42% in the DRC and ARR in both the PA and non-PA groups. The degree of variability was substantially higher than the assays' analytical CV. Sixty-two patients (38%) with PA had at least one ARR below 70 pmol/L:mU/L (2.4 ng/dL:mU/L), a cut-off for first-line screening of PA. CONCLUSIONS: Significant intra-individual variability in PAC, DRC, and hence ARR occurs in a large proportion of patients being investigated for PA. These findings support the need for at least 2 ARR before PA is excluded or further investigated.

Expanding the Material Search Space for Multivalent Cathodes.

Multivalent batteries are an energy storage technology with the potential to surpass lithium-ion batteries; however, their performance have been limited by the low voltages and poor solid-state ionic mobility of available cathodes. A computational screening approach to identify high-performance multivalent intercalation cathodes among materials that do not contain the working ion of interest has been developed, which greatly expands the search space that can be considered for material discovery. This approach has been applied to magnesium cathodes as a proof of concept, and four resulting candidate materials [NASICON V2(PO4)3, birnessite NaMn4O8, tavorite MnPO4F, and spinel MnO2] are discussed in further detail. In examining the ion migration environment and associated Mg2+ migration energy in these materials, local energy maxima are found to correspond with pathway positions where Mg2+ passes through a plane of anion atoms. While previous studies have established the influence of local coordination on multivalent ion mobility, these results suggest that considering both the type of the local bonding environment and available free volume for the mobile ion along its migration pathway can be significant for improving solid-state mobility.

Impact of dedicated multidisciplinary service on patient selection and outcomes for surgical treatment of primary aldosteronism.

BACKGROUND: Primary aldosteronism is the most common surgically curable cause of endocrine hypertension. Management of the unilateral subtype of primary aldosteronism with adrenalectomy requires multidisciplinary input. It is unclear if a dedicated endocrine hypertension service confers better outcomes compared to standard care offered by individual clinicians. METHODS: In this retrospective study, patients from the Monash University Endocrine Surgery Database were divided into either the endocrine hypertension service group, where patients were managed by a dedicated multidisciplinary team, or the standard group, where patients were managed by individual clinicians. The comparisons included patient selection for surgery, perioperative blood pressure control, and surgical cure rate. RESULTS: Despite similar perioperative blood pressure, patients in the endocrine hypertension service group (n = 41) were on fewer antihypertensive medications (1 vs 2, P = .011) compared to the standard group (n = 55). A larger proportion of patients in the endocrine hypertension service group had either bilateral adrenal nodules or no adrenal lesions on computed tomography (41% vs 18%, P = .013). Patients in the standard group had larger adrenal lesions on computed tomography (median 15 mm vs 10 mm, P = .032). Postoperatively, the biochemical cure rate was higher in the endocrine hypertension service group at 6 to 12 months (97% vs 76%, P = .021). CONCLUSION: Patients managed by endocrine hypertension service were more likely to be diagnosed with surgically curable primary aldosteronism without a unilateral adrenal adenoma on imaging, required fewer medications for perioperative blood pressure control, and experienced superior postoperative outcomes. Referral to a dedicated endocrine hypertension service is recommended for patients with primary aldosteronism who wish to pursue a surgical cure.

Impact of Intraprocedural Sedation on Adrenal Vein Sampling without Corticotropin Stimulation.

See also the editorial by Georgiades in this issue.

Detecting primary aldosteronism in Australian primary care: a prospective study.

OBJECTIVE: To assess the identification of primary aldosteronism (PA) in newly diagnosed, treatment-naïve patients with hypertension by screening in primary care. DESIGN: Prospective study. SETTING: General practices in the South Eastern Melbourne Primary Health Network with at least three general practitioners and general practices elsewhere in Victoria that had referred patients to the Endocrine Hypertension Clinic at Monash Health, 2017-2020. PARTICIPANTS: Adults (18-80 years) with newly diagnosed hypertension (measurements of systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on at least two occasions) and not taking antihypertensive medications were screened for PA by assessing their aldosterone-to-renin ratio (ARR). Participants with two ARR values exceeding 70 pmol/mU underwent saline suppression testing at the Endocrine Hypertension Service (Monash Health) to confirm the diagnosis of PA. MAIN OUTCOME MEASURES: Prevalence of PA (number of patients with confirmed PA divided by number screened). RESULTS: Sixty-two of 247 screened participants had elevated ARR values on screening (25%); for 35 people (14%; 95% CI, 10-19%), PA was confirmed by saline suppression testing. Baseline characteristics (mean age, sex distribution, median baseline blood pressure levels, and serum potassium concentration) were similar for people with or without PA. CONCLUSION: PA was diagnosed in 14% of patients with newly diagnosed hypertension screened by GPs, indicating a potential role for GPs in the early detection of an important form of secondary hypertension for which specific therapies are available.

Preoperative mineralocorticoid receptor antagonist reduces postoperative hyperkalaemia in patients with Conn syndrome.

BACKGROUND: The preoperative use of mineralocorticoid receptor antagonists (MRA) in patients with unilateral forms of primary aldosteronism (PA) is not standardized. The current Endocrine Society Guidelines do not specifically recommend MRA treatment before surgery. It is unclear whether preoperative MRA can optimize perioperative blood pressure and potassium control, and reduce the incidence of postoperative hyperkalaemia. OBJECTIVE: This study aimed to investigate the effect of MRA on the incidence of postoperative hyperkalaemia in addition to perioperative blood pressure and potassium concentration in patients undergoing unilateral adrenalectomy for the treatment of PA. DESIGN: Retrospective cohort study. SETTING: Tertiary referral centres, Victoria, Australia. PATIENTS: A total of 96 patients who were diagnosed with unilateral forms of PA: 73 patients ('MRA' group) received preoperative MRA while 23 patients ('No-MRA' group) did not. RESULTS: The prevalence of postoperative hyperkalaemia was significantly higher in the 'No-MRA' group at 2-4 weeks after surgery, compared to the 'MRA' group (35% vs. 11%, p = .014). In a logistic regression, the use of MRA significantly predicted a lower incidence of postoperative hyperkalaemia after adjusting for age, sex, baseline aldosterone-to-renin ratio, potassium and preoperative eGFR. Before surgery, patients in the 'MRA' group had normalized blood pressure and potassium concentration requiring fewer antihypertensive medications and no potassium supplements. CONCLUSION: Preoperative MRA use was associated with optimal perioperative blood pressure and normalized serum potassium in addition to a lower incidence of postoperative hyperkalaemia. MRA should be considered standard treatment for patients awaiting surgery for PA.

Minimizing hydrogen vacancies to enable highly efficient hybrid perovskites.

Defect-induced non-radiative losses are currently limiting the performance of hybrid perovskite devices. Experimental reports have indicated the existence of point defects that act as detrimental non-radiative recombination centres under iodine-poor synthesis conditions. However, the microscopic nature of these defects is still unknown. Here we demonstrate that hydrogen vacancies can be present in high densities under iodine-poor conditions in the prototypical hybrid perovskite MAPbI3 (MA = CH3NH3). They act as very efficient non-radiative recombination centres with an exceptionally high carrier capture coefficient of 10-4 cm3 s-1. By contrast, the hydrogen vacancies in FAPbI3 [FA = CH(NH2)2] are much more difficult to form and have a capture coefficient that is three orders of magnitude lower. Our study unveils the critical but overlooked role of hydrogen vacancies in hybrid perovskites and rationalizes why FA is essential for realizing high efficiency in hybrid perovskite solar cells. Minimizing the incorporation of hydrogen vacancies is key to enabling the best performance of hybrid perovskites.

Comparison of ambulatory blood pressure between patients with primary aldosteronism and other forms of hypertension.

OBJECTIVE: Primary aldosteronism (PA) is a potentially curable cause of hypertension associated with worse cardiovascular prognosis than blood pressure-matched essential hypertension (EH). Effective targeted treatment for PA is available with the greatest benefit seen if treatment is started early, prior to the development of end-organ damage. However, PA is currently substantially under-diagnosed. The standard screening test for PA, the aldosterone-to-renin ratio (ARR), is performed infrequently in both primary and tertiary care. In contrast, ambulatory blood pressure monitoring (ABPM) is frequently utilized in the assessment of hypertension. The aim of this study was to compare ABPM parameters in hypertensive patients with and without PA, in order to identify features of ABPM associated with PA that can prompt screening. STUDY DESIGN: Patients with PA (n = 55) were identified from a tertiary clinic specializing in the management of endocrine causes of hypertension whilst the controls (n = 389) were consecutive patients with hypertension but without a known diagnosis of PA who were referred for ABPM. RESULTS: In this study, PA patients were younger and had higher 24-h, day, and night-time blood pressure compared with controls despite similar number of antihypertensive medications. However, there was no significant difference in nocturnal dipping or day-night blood pressure variability between the two groups. CONCLUSIONS: An elevated ambulatory blood pressure in patients on multiple antihypertensives could suggest underlying PA but in the absence of other distinguishing features, ABPM could not reliably differentiate PA from other forms of hypertension. Routine biochemical screening for PA remained the most reliable way of detecting this treatable secondary cause of hypertension.

Impact of Victoria's first dedicated endocrine hypertension service on the pattern of primary aldosteronism diagnoses.

BACKGROUND: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk. AIMS: To analyse the impact of Victoria's first dedicated endocrine hypertension service (EHS) on the pattern of PA diagnosis. METHODS: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (n = 267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2) and Year 3 (Y3), based on their first visit. RESULTS: The proportion of primary care referrals increased (20% in Y1, 47% in Y2, 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1, 14% in Y2, 19% in Y3). Among PA patients, the median duration of hypertension prior to their first visit decreased (11 years in Y1, 10 years in Y2, 7 years in Y3), and the prevalence of end-organ damage decreased (44% in Y1, 42% in Y2, 33% in Y3). Targeted management of PA improved clinical and biochemical outcomes. The average blood pressure reduction following targeted management increased from 16/12 mmHg in Y1 to 23/12 mmHg in Y3. CONCLUSION: The EHS, with its strong component of general practitioner engagement, led to increased primary care referrals and PA detection earlier in the course of hypertension. Referred patients were on fewer antihypertensives and had less end-organ damage which simplified the diagnostic process, allowing targeted treatment to be commenced earlier and patient outcomes optimised.

A Multicenter Study of Neutrophil-to-Lymphocyte Ratio in Primary Aldosteronism.

BACKGROUND: Hypertensive patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than those with blood pressure-matched essential hypertension. The excess cardiovascular consequences of PA can be attributed to the proinflammatory effect of excessive aldosterone and mineralocorticoid receptor activation in a range of peripheral tissues and cell types. The neutrophil-to-lymphocyte ratio (NLR) is a widely available marker of inflammation which has been shown to predict cardiovascular outcome in the general population. This study aims to evaluate the use of NLR as a potential biomarker of PA and PA severity. METHODS: Patients with PA (n = 355) were identified from 2 large PA databases in Australia and China, while controls (n = 222) were patients with hypertension who were referred for assessment but did not meet the diagnostic criteria for PA. The NLR was retrospectively collected from routine full blood examination, prior to commencement of targeted treatment for PA. RESULTS: The NLR did not differ between PA patients and hypertensive controls (median 2.3 and 2.4, P = 0.563). However, among patients with PA, the NLR was positively correlated with baseline and post-saline aldosterone levels (r = 0.22 and P < 0.001 for both) and negatively correlated with serum potassium (r = -0.15, P = 0.006). Furthermore, in a logistic regression analysis of data from patients with PA, the NLR predicted the presence of comorbid chronic kidney disease (CKD) (defined as estimated glomerular filtration rate <60 mL/min/1.73m2) with an odds ratio of 1.5 (P = 0.003). CONCLUSION: While the NLR did not distinguish PA from controls, it was a marker of PA severity, being associated with aldosterone concentration as well as the presence of CKD. A prospective study is needed to further clarify the role of NLR in predicting end-organ damage associated with PA.

First-principles study of CaB12H12 as a potential solid-state conductor for Ca.

Calcium dodecahydro-closo-dodecaborate, CaB12H12, was calculated to have a percolating Ca migration path with low activation barrier (650 meV). The formation of Ca vacancies required for diffusion was calculated to be thermodynamically feasible by substitution of Ca with Al, Bi, or a number of trivalent rare-earth cations.

Li5VF4(SO4)2: A Prototype High-Voltage Li-Ion Cathode.

A Li-rich polyanionic compound based on V3+ with a previously unknown structure, Li5VF4(SO4)2, has been developed as a high-voltage cathode material for Li-ion batteries. The solvothermal preparation of this material, crystal structure solution, and initial electrochemical characterization are presented. An analysis based on density functional theory electronic structure calculations suggests that a high voltage close to 5 V is required to extract two Li ions and to reach the oxidation state of V5+. However, the use of conventional carbonate-based electrolytes, which exhibit increasing degradation above a potential of 4.3 V, does not permit the full capacity of this compound to be achieved at this time.

Anomalous Auger Recombination in PbSe.

Using first-principles approaches we find that the Auger recombination in PbSe is anomalous in three distinct ways. First, the direct Auger coefficient is 4 orders of magnitude lower than that of other semiconductors with similar band gaps, a result that can be attributed to the lack of involvement of a heavy-hole band. Second, phonon-assisted indirect Auger recombination prevails, contrary to the common belief that direct Auger is dominant in narrow-gap semiconductors. Third, an unexpectedly weak temperature dependence of the Auger coefficient is observed, which we can now attribute to the indirect nature of the Auger process. The widely accepted explanation of this behavior in terms of an unusual temperature dependence of the band gap is only a secondary effect. Our results elucidate the mechanisms underlying the anomalous Auger recombination in IV-VI semiconductors in general, which is critical for understanding and engineering carrier transport.

Utility of adrenocorticotropic hormone in adrenal vein sampling despite the occurrence of discordant lateralization.

BACKGROUND: Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. OBJECTIVE: To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. DESIGN: A retrospective cross-sectional analysis of AVS results and postoperative patient outcomes. SETTING: Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. MEASUREMENTS: Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure. RESULTS: Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI >3 pre-ACTH and LI >2 post-ACTH was predictive of a biochemical cure. CONCLUSION: Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.

Age- and sex-specific reference ranges are needed for the aldosterone/renin ratio.

OBJECTIVE: Current Endocrine Society Clinical Practice Guidelines use a specific aldosterone/renin ratio (ARR) threshold to screen for primary aldosteronism (a treatable disease causing up to 15% of hypertension in primary care) in all patients. We sought to characterize demographic variations in the ARR, hypothesizing a need for age- and sex-specific reference ranges to improve the accuracy of the test. DESIGN: Retrospective cross-sectional analysis of ARR measurements at a single tertiary hospital from December 2016 to June 2018. PATIENTS: A total of 442 patients with clinically indicated ARR were included, after excluding those who were on spironolactone or the oral contraceptive pill, were pregnant or had an existing adrenal condition. MEASUREMENTS: Aldosterone, renin and the ARR. RESULTS: Among those aged 20-39 years (n = 74), females had significantly higher median aldosterone (369 vs 244 pmol/L, P = .028), lower median renin (17.0 vs 27.6 mIU/L, P = .034) and higher median ARR (20.7 vs 10.3 (pmol/L)/(mIU/L), P = .001) than males, despite having lower systolic (135 vs 145 mmHg, P = .021) and diastolic (89 vs 96.5 mmHg, P = .007) blood pressure. The ≥ 60-year age group (n = 157) also had significant sex differences in the ARR. With increasing age (20-39 vs ≥ 60 years), there was a significant fall in plasma aldosterone in females (369 pmol/L vs 264 pmol/L, P = .005), with no change observed in males. CONCLUSIONS: For those 20-39 years old, aldosterone and the ARR are significantly higher in females despite a lower systolic and diastolic BP, highlighting the potential for false-positive results. Our findings indicate the need for prospective studies with a control population to define age- and sex-specific ARR reference ranges.

Saline suppression test parameters may predict bilateral subtypes of primary aldosteronism.

BACKGROUND: The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA) whilst adrenal vein sampling (AVS) is used to determine whether the aldosterone hypersecretion is unilateral or bilateral. An accurate prediction of bilateral PA based on SST results could reduce the need for AVS. AIM: We sought to identify SST parameters that reliably predict bilateral PA. METHODS: The results from 121 patients undergoing SSTs at Monash Health from January 2010 to January 2018 including screening blood tests, imaging, AVS and histopathology results were evaluated. Patients were subtyped into unilateral or bilateral PA based on AVS and surgical outcomes. RESULTS: Of 113 patients with confirmed PA, 33 had unilateral disease whilst 42 had bilateral disease. In those with bilateral disease, plasma aldosterone concentration (PAC) was significantly lower post-SST, together with a significant fall in the aldosterone-renin ratio (ARR). The combination of PAC < 300 pmol/L and a reduction in ARR post-SST provided 96.8% specificity in predicting bilateral disease. Eighteen of 39 patients (49%) with bilateral PA could have avoided AVS using these criteria. CONCLUSION: A combination of PAC < 300 pmol/L and a lower ARR post-SST could reliably predict bilateral PA. An independent cohort will be needed to validate these findings.