Primary
aldosteronism encompasses 2 major underlying causes: (1)
aldosterone producing
adenoma and (2) bilateral adrenal
hyperplasia. In addition to the
aldosterone excess, increased production of other compounds of the steroidogenic pathways may be involved. Until recently, most studies examined the production of
steroids other than
aldosterone in
tumor tissue, urine, or peripheral plasma samples, but several new studies have also addressed
steroid levels in adrenal venous blood samples using liquid chromatography tandem mass spectrometry. Plasma and tissue levels of several precursors of
aldosterone with
mineralocorticoid activity are higher in patients with
aldosterone producing
adenomas than in those with bilateral
hyperplasia. These include
corticosterone,
deoxycorticosterone, and their 18-hydroxylated metabolites. Similarly, urinary, peripheral, and adrenal venous concentrations of the hybrid
steroids 18-oxocortisol and
18-hydroxycortisol are higher in patients with
aldosterone producing
adenomas than in bilateral
hyperplasia. Differences in the pathophysiology and in clinical and biochemical phenotypes caused by
aldosterone producing
adenomas and bilateral adrenal
hyperplasia may be related to the differential expression of steroidogenic
enzymes, and associated to specific underlying somatic mutations. Correct appreciation of differences in
steroid profiling between
aldosterone producing
adenomas and bilateral adrenal
hyperplasia may not only contribute to a better understanding of the pathogenesis of primary
aldosteronism but may also be helpful for future subtyping of primary
aldosteronism.