mineralocorticoidrelated

Mineralocorticoid-related refers to the physiological and clinical aspects governed by mineralocorticoids, principally aldosterone, and the receptors and signaling pathways they engage. Aldosterone is produced in the adrenal cortex and primarily regulates electrolyte balance, extracellular fluid volume, and blood pressure by promoting sodium reabsorption and potassium excretion in the kidney, especially in the collecting ducts. Mineralocorticoid signaling also influences other tissues such as the colon, sweat glands, and, to a lesser extent, the heart and brain.

The key molecular mediator is the mineralocorticoid receptor (MR), a nuclear receptor expressed in renal tubules and other tissues. aldosterone binding to MR stimulates transcription of target genes that increase epithelial sodium channels (ENaC) and Na+/K+-ATPase activity, enhancing sodium reabsorption and potassium secretion. Cortisol can bind MR with high affinity, so locally active 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol to prevent inappropriate MR activation. This protective mechanism helps to maintain selective aldosterone effects in mineralocorticoid target tissues.

Regulation of mineralocorticoid activity occurs largely through the renin-angiotensin-aldosterone system (RAAS). Low blood pressure or low sodium stimulates renin release, increasing angiotensin II and aldosterone production. Disorders related to mineralocorticoids include primary hyperaldosteronism (often from an adrenal adenoma or bilateral hyperplasia) with hypertension and hypokalemia, and secondary hyperaldosteronism driven by RAAS activation. Hypoaldosteronism (e.g., Addison disease) can cause hyponatremia and hyperkalemia. Pseudohypoaldosteronism and Liddle syndrome represent defects in MR signaling or ENaC function, causing salt wasting or hypertension, respectively.

Diagnosis typically involves measuring plasma aldosterone concentration and plasma renin activity or ratio, sometimes combined with imaging. Treatment uses mineralocorticoid receptor antagonists (spironolactone, eplerenone), potassium-sparing diuretics, and addressing underlying causes, including surgical removal of aldosterone-producing tumors when present.