T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity.

Primary aldosteronism (PA) is a common, under-recognised cause of hypertension carrying cardiovascular and renal risk beyond blood pressure alone. Management requires accurate subtype diagnosis: lateralised disease may be cured by adrenalectomy, whereas bilateral disease usually requires mineralocorticoid receptor antagonist therapy. The PASO criteria standardised postsurgical outcome assessment and showed that biochemical remission is achieved in most patients with adrenal vein sampling-confirmed lateralised disease, whereas clinical remission is variable, reflecting pre-existing hypertensive burden, age and sex. The PAMO criteria extend this framework to medically treated PA and show that complete clinical response is uncommon. At the tissue level, the HISTALDO classification distinguishes classical lateralised disease, typically caused by an aldosterone-producing adenoma, from non-classical disease, dominated by multiple micronodules; the latter carries a higher risk of postsurgical persistent or recurrent aldosteronism. These observations support a broader model in which PA forms a continuous rather than binary spectrum, from subclinical renin-independent aldosteronism and age-related micronodular remodelling to overt bilateral and lateralised disease. Tissue omics studies support a model in which aldosterone-producing lesions progress from zona glomerulosa cells to micronodules and adenomas. KCNJ5-mutated adenomas may follow a direct route, arising without a detectable micronodule stage, possibly because reduced oxidative stress favours early cell survival and expansion. The adenoma is therefore not a static endpoint but a maturing tissue, in which immune remodelling and changes in cell survival mechanisms may shape progression towards a hypersecretory state. Together, these findings link clinical phenotype to adrenal tissue biology and support a dynamic, genotype-modulated model of PA pathogenesis.