Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey.

BACKGROUND: Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Many patients experience preventable end-organ injury due to delayed or missed diagnosis but data on the experience of patients are limited. METHODS: We evaluated the lived experience of PA and determines factors associated with diagnostic delay through an international anonymous online cross-sectional survey, codesigned by researchers and PA consumers. We distributed the survey through academic medical centers, Amazon Mechanical Turk, Twitter, PA patient advocacy groups, and hypertension support groups on Facebook between March 21 and June 5, 2022. RESULTS: Of 684 eligible respondents, 66.5% were women. Diagnostic delay (defined as ≥5 years between the diagnosis of hypertension and PA) was reported in 35.6%. Delay was more likely in women than in men (odds ratio, 1.55 [95% CI, 1.10-2.20]) and respondents with ≥3 comorbidities versus none (odds ratio, 1.77 [95% CI, 1.05-3.02]), ≥10 symptoms versus none (odds ratio, 2.73 [95% CI, 1.74-4.44]), and on ≥4 antihypertensive medications versus none (odds ratio, 18.23 [95% CI, 6.24-77.72]). Three-quarters of patients (74.4%) experienced reduced symptom burden following targeted PA treatment. Quality of life improved in 62.3% of patients, and greater improvement was associated with being a woman (odds ratio, 1.42, [95% CI, 1.02-1.97]), receiving adrenalectomy (odds ratio, 2.36 [95% CI, 1.67-3.35]), and taking fewer antihypertensive medications following diagnosis (odds ratio, 5.28 [95% CI, 3.55-7.90]). CONCLUSIONS: One-third of patients with PA experienced prolonged diagnostic delays. Targeted treatment led to reduced symptom burden and improved quality of life. Gender differences in diagnostic delay and symptom burden are prominent. These findings suggest that routine screening for PA at the onset of hypertension may reduce diagnostic delay and facilitate timely diagnosis.

Cost-effectiveness of screening for primary aldosteronism in hypertensive patients in Australia: a Markov modelling analysis.

BACKGROUND: Primary aldosteronism affects 3-14% of hypertensive patients in the primary care setting and up to 30% in the hypertensive referral units. Although primary aldosteronism screening is recommended in patients with treatment-resistant hypertension, diagnosis at an earlier stage of disease may prevent end-organ damage and optimize patient outcomes. METHODS: A Markov model was used to estimate the cost-effectiveness of screening for primary aldosteronism in treatment and disease (cardiovascular disease and stroke) naive hypertensive patients. Within the model, a 40-year-old patient with hypertension went through either the screened or the unscreened arm of the model. They were followed until age 80 or death. In the screening arm, the patient underwent standard diagnostic testing for primary aldosteronism if the screening test, aldosterone-to-renin ratio, was elevated above 70 pmol/l : mU/l. Diagnostic accuracies, transition probabilities and costs were derived from published literature and expert advice. The main outcome of interest was the incremental cost effectiveness ratio (ICER). RESULTS: Screening hypertensive patients for primary aldosteronism compared with not screening attained an ICER of AU$35 950.44 per quality-adjusted life year (QALY) gained. The results were robust to different sensitivity analyses. Probabilistic sensitivity analysis demonstrated that in 73% of the cases, it was cost-effective to screen at the commonly adopted willingness-to-pay (WTP) threshold of AU$50 000. CONCLUSION: The results from this study demonstrated that screening all hypertensive patients for primary aldosteronism from age 40 is cost-effective. The findings argue in favour of screening for primary aldosteronism before the development of severe hypertension in the Australian healthcare setting.

Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization.

CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).