Hyperaldosteronism

 

• Pathophysiology and causes

  Excess aldosterone, a mineralocorticoid.

  Renin-angiotensin-aldosterone system (RAAS) refresher:

  1. ↓BP triggers renin release from juxta-glomerular cells in kidney.
  2. Renin converts angiotensinogen to angiotensin I.
  3. ACE converts angiotensin I to angiotensin II.
  4. Angiotensin II has many effects, including triggering aldosterone release from the zona glomerulosa (the outer section) of the adrenal cortex.
  5. Aldosterone acts on principals cells in distal collecting tubule of kidney to ↑sodium reabsorption through ENaC (apical) and Na+/K+ exchanger (basolateral).

  Causes of primary hyperaldosteronism:

  • Conn's syndrome: adrenal adenoma. The name is often synonymous with primary aldosteronism.
  • Bilateral adrenal hyperplasia (BAH), which is usually idiopathic. Not to be confused with congenital adrenal hyperplasia.
  • Glucocorticoid remediable aldosteronism (GRA): autosomal dominant inherited disease. ↑Aldosterone synthase sensitivity to ACTH which leads to persistent ↑aldosterone.

  Secondary hyperaldosteronism:

  • Juxtaglomerular cell tumour.
  • Bartter's syndrome.

• Signs and symptoms

  • ↑BP, often mild.
  • Nocturia
  • Lethargy and altered mood.
  • Rarely, weakness and cramps.

• Differential diagnosis

  The following mimic features of hyperaldosteronism but do not involve aldosterone increase.

  Apparent mineralocorticoid excess

  • Autosomal recessive condition leading to failure to break down cortisol to cortisone in the kidney.
  • Licorice can also be a cause.

  Liddle's syndrome

  • Aka pseudoaldosteronism.
  • Autosomal dominant condition leading to hyperactive ENaC.
  • Treat with amiloride.

• Investigations

  U&E:

  • ↓K+, sometimes with ↑pH as consequence.
  • Na+ is usually normal due to other regulatory mechanisms.

  Renin-aldosterone:

  • ↑ or inappropriately normal aldosterone.
  • ↓Renin in response to high aldosterone.
  • ↑Aldosterone:Renin ratio.

  Locating source:

  • High-res CT or MRI of adrenals.
  • Adrenal vein sampling if imaging is -ve.

• Management

  • Conn's: spironolactone until surgery, which is the definitive treatment.
  • BAH: aldosterone antagonists including amiloride and spironolactone.