see also:

• aldosterone antagonists
• hypoaldosteronism
• aldosterone
• hypertension
• endocrinology
• physiology main index

• hyperaldosteronism is due to excessive aldosterone secretion from the adrenals and causes hypertension with hypokalaemia and metabolic alkalosis
• it is characterized by a high serum level of aldosterone and a low serum renin level if primary and a high serum renin level is secondary
• the same clinical features but with normal or low levels of aldosterone may be caused by pseudoaldosteronism which may be due to:
  • licorice ingestion
    • licorice inhibits the 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2) enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol
  • high gluocorticosteroid levels
  • Liddle's syndrome (an extremely rare genetic disorder)
  • apparent mineralocorticoid excess syndrome a rare AR disorder

• note: serum renin levels will be low
• idiopathic bilateral adrenal cortical hyperplasia (70% of cases)
• adrenal adenoma
  • Conn's syndrome
  • large aldosterone-secreting adrenal adenomas
    • tend to be picked up on CT scans given their larger size
    • tend to have pathogenic KCNJ5 variants (30-40% of large aldosterone-secreting adrenal adenomas)
    • cells paradoxically resemble the cortisol- rather than aldosterone-secreting zone of the normal adrenal gland
  • ZG-like aldosterone-secreting adrenal adenomas
    • tend to have pathogenic CACNA1D, ATP1A1 and ATP2B3 variants
    • tend to be smaller and missed on CT scans
    • cells resemble the physiological aldosterone-secreting cells of the adrenal zona glomerulosa (ZG)
  • daily transient adrenal adenoma hyper-aldosteronism
    • discovered in 2023 ¹⁾
      • requires 24hr urine aldosterone to detect as serum levels may miss the transient rises
      • caused by a somatic mutation in aldosterone-producing adenomas of the gene which produces a protein called cell adhesion molecule 1 (CADM1)
      • seems to the the cause of 5-10% of cases of hypertension
      • Rx is unilateral adrenalectomy
• adrenal carcinoma is an extremely rare cause
• glucocorticoid remediable aldosteronism (aldosterone synthase hyperactivity), is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

• this is due to overactivity of the renin–angiotensin–aldosterone system (RAAS) resulting from high renin levels
  • massive ascites
  • left ventricular failure (LVF)
  • cor pulmonale
  • a renin-producing tumor leads to increased aldosterone eg. juxtaglomerular cell tumor
  • renal artery stenosis causes reduced blood supply across the juxtaglomerular apparatus which stimulates the production of renin
  • hyporeabsorption of sodium (as seen in Bartter and Gitelman syndromes)

• elevated serum aldosterone
• serum aldosterone:renin ratio to determine primary vs secondary
• serum cortisol to exclude cortisol causes