Diagnosis of primary aldosteronism: Novel workup strategies and biochemical tools

Primary aldosteronism (PA) is a prevalent yet underdiagnosed cause of hypertension, significantly contributing to cardiovascular morbidity. Despite established guidelines, the diagnostic pathway for PA remains complex, hindered by analytical and physiological variability in aldosterone and renin measurements, and limitations of the aldosterone-to-renin ratio (ARR) for the screening. These challenges often lead to delayed diagnosis and suboptimal patient outcomes. This chapter critically reviews emerging innovations designed to overcome these barriers, exploring advancements across several domains. We examine novel applications of traditional biomarkers, such as renin suppression and angiotensin II-based ratios, alongside the utility of non-invasive salivary as well as urinary aldosterone measurements. Furthermore, the integration of steroidomics, proteomics, and molecular profiling, including microRNAs and extracellular vesicles, is discussed to offer deeper biochemical insights. Finally, transformative potential of functional imaging techniques, particularly CXCR4-targeted PET, and the increasing role of machine learning in refining diagnostic algorithms and identifying novel biomarkers is explored. These advancements in novel biomarkers and work-up strategies promise to enhance the sensitivity, specificity, and practicality of PA diagnosis, facilitating earlier intervention and improving patient care.