PA is defined as inappropriately elevated aldosterone production in the setting of low plasma renin. PA is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist.

PA commonly presents itself as:

• Aldosterone Producing Adenoma (APA)

• Bilateral Hyperaldosteronism (BHA)

APA is a tangible form of disease and can be seen as nodules on the adrenal, while BHA is an elusive concept, which has lacked a pathophysiological mechanism for many years.

CAH is a term used collectively for a group of autosomal recessive genetic defects in cortisol biosynthesis.

• 21-hydroxylase (CYP21A2) deficiency (21OHD) is the most common form of CAH, accounting for more than 90% of all CAH cases. Based on the presence or absence of cortisol insufficiency, diagnosis of 21OHD is routinely classified into classic and nonclassic forms, respectively.

• Impaired cortisol production relieves negative feedback to the hypothalamus and the pituitary gland, which in response amplify the secretion of corticotropin-releasing hormone (CRH) and ACTH, respectively, resulting in hyperplasia of the adrenal cortex.

AVS is required to distinguish unilateral from bilateral aldosterone sources in primary aldosteronism, and cortisol is used for AVS data interpretation, but cortisol has several pitfalls. We are working to explore the utility of several other steroids in PA subtyping, both during AVS, as well as in peripheral serum. We have found 11β-hydroxyandrostenedione and 11-deoxycortisol to be superior to cortisol for AVS data interpretation. Single assay multi-steroid panels measured in peripheral serum are helpful in stratified PA subtyping and have the potential to circumvent AVS in a subset of patients with PA.