Home measurement of 24-hour corticosteroid dynamics in primary aldosteronism

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Abstract

Primary aldosteronism (PA) affects 5–20% of the hypertensive population and is associated with increased cardiovascular and metabolic risks compared with primary hypertension. PA is significantly underdiagnosed partly due to our inability to capture the pulsatile variability of aldosterone over 24 hours in clinical settings. To gain insight into steroid secretion patterns in PA we applied multiplex 24-hour profiling of free corticosteroids concentrations in subcutaneous tissue microdialysate in 60 PA patients and 215 healthy individuals in a home setting (NCT02934399). PA profiles displayed a diurnal, pulsatile hypersecretion of aldosterone compared with healthy participants. Nocturnal and early morning hypersecretion of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol enabled the identification of unilateral PA cases, candidates for surgical treatment. Indeed, normalisation of aldosterone hypersecretion was observed after adrenalectomy. Using dynamic markers extracted from the 24-hour time series our machine learning classifier achieved sensitivity of 88% and specificity of 80% to diagnose PA. We demonstrate that 24-hour dynamic hormone profiling in the home setting has the potential to transform endocrine diagnostics from assessing single point hormone levels to evaluation of dynamic patterns, which can change clinical practice not only for the diagnosis of PA, but also for other hormone excess and deficiency syndromes.

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