Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery

Recent advances in molecular pathology have elucidated the genetic underpinnings of benign aldosterone- and cortisol-producing adrenal lesions, identifying genes encoding mainly potassium and voltage-gated calcium channels in primary aldosteronism (PA), and PRKACA, PRKAR1A, ARMC5 in hypercortisolism. These insights are increasingly guiding precise, function-preserving surgery, such as mini back scope adrenalectomy (MBSA) at high-volume centers with reduced morbidity and risk of adrenal insufficiency, even in complex bilateral cases. Postoperative pathological analysis assessing hormone secretion and genetics provides prognostic information and directs further therapy, whether medical or surgical. A modern approach to PA and hypercortisolism, influenced by an enhanced understanding of the molecular pathophysiology, is likely to improve outcomes and expand adrenalectomy usage and indications as the morbidity and mortality associated with these endocrinopathies are increasingly recognized.