Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening

Abstract

Context Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277 to 415.5 pmol/L) using immunoassay. Aim To evaluate intraindividual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least two screenings. Results The median intraindividual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least two aldosterone levels <15 ng/dL and 16.2% had mean aldosterone levels <15 ng/dL. A lower cut-off of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for two aldosterone measurements and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on one or two assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering anti-hypertensive medications, PA lateralization, hypokalemia, age and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negative test in a single screening for PA. Therefore, PA screening should be based in at least two screenings with concomitant aldosterone and renin measurements.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism

“…The algorithm for PA investigation followed the 2016 Endocrine Society Guideline for PA management [2]. In our Institution, a positive screening for PA, defined as an aldosterone/DRC ratio > 2 ng/ dl/μIU/ml (or 55.5 pmol/l/μIU/ml) with concomitant aldosterone levels > 10 ng/dl (or 277 pmol/l), has a true positive rate of 95 % for PA diagnosis [23].…”

Primary Aldosteronism Prevalence – An Unfolding Story

“…[12] Less stringent criteria increase the detection rates of both advanced and mild forms of PA. [26][27][28][29] Two recent systematic reviews of ARR testing found that the clinical performance of ARR varied widely with the patient population, clinical setting, and thresholds used, rendering sensitivities from 10% to 100%. [30,31] Considering the dynamic fluctuations of renin and aldosterone in response to a large number of determinants, [32][33][34] the current Endocrine Society guideline proposes confirmatory testing in most patients with positive screening results in order to solidify the PA diagnosis. [12] Notably, however PA has been diagnosed in individuals with ARR values lower than the commonly used threshold for PA, indicating the limitations of arbitrary screening criteria in capturing the broad continuum of inappropriate aldosterone production.…”

“…Considering the dynamic fluctuations of renin and aldosterone in response to a large number of determinants [32][33][34], the current Endocrine Society guideline proposes confirmatory testing in most patients with positive screening results to solidify the PA diagnosis [12]. Notably, however, PA has been diagnosed in individuals with ARR values lower than the commonly used threshold for PA, indicating the limitations of arbitrary screening criteria in capturing the broad continuum of inappropriate aldosterone production.…”

Avaliação dos testes da furosemida endovenosa e oral no diagnóstico do hiperaldosteronismo primário

“…Nesse cenário, o valor de corte de 10 µU/mL no tempo de 2 horas aumentou a sensibilidade e especificidade para o diagnóstico de HP. Embora, essa conclusão seja preliminar, já que somente 6 casos com HA com renina suprimida foram analisados, foi considerado o valor de corte de renina de 10 µU/mL como o mais adequado para o TFO no tempo 2 horas.Recentemente, diversos estudos demonstraram uma importante variabilidade intraindividual nos valores de aldosterona basais em pacientes com HP15,64 . Yozamp et al64 mostraram que aproximadamente 30% dos pacientes com HP tiveram pelos menos um valor de aldosterona <10 ng/dL e 50% dos pacientes pelo menos um valor de aldosterona <15 ng/dL.…”