Diagnosis

Hypoaldosteronism

Etiology

Cause [zwp][dad]

1. Defective synthesis: Hyperreninemic hypoaldosteronism (rare)

   • Immaturity of aldosterone synthetic enzymes in infants

   • Primary adrenal insufficiency (enzyme defect: aldosterone synthase deficiency)

   • Critically ill patients (peritonitis, liver failure, septic shock, pneumonia, cholangitis): diminish aldosterone synthesis by diverting substrate to the production of cortisol

   • Delayed recovery of the suppressed gland after contralateral adrenalectomy

   • Drug-induced diminished synthesis

   • Discontinuation of drugs with mineralocorticoid activity after prolonged use

2. Defective release: Hyporeninemic hypoaldosteronism (most common)

   1. Congenital (rare: 1 per 80,000)

   2. Acquired (more frequent due to diabetes and RAAS-medications)

      • Diabetes

      • Various nephropathies

      • Autonomic neuropathy

      • Sickle cell disease

      • HIV disease

3. Medications: NSAIDs, COX-2 inhibitors, ACEI/ARBs, Heparin, β-blockers, Trimethoprim, MRBs, calcineurin inhibitors, potassium-sparing diuretics (spironolactone), pentamidine, ketoconazole, dopamine

4. Aldosterone resistance:

   • Genetic

     • Autosomal dominant pseudohypoaldosteronism

     • Autosomal recessive pseudohypoaldosteronism

   • Acquired

     • Urinary tract infection and obstructive uropathy

     • Medications

     • Downregulation of mineralocorticoid receptor in renal tubules (solid organ transplant)

Pathophysiology

1. Renin --> Angiotensin --> Aldosterone (RAA axis) regulates:

   • Sodium (Na)

   • Potassium (K)

   • Extravellular compartment fluid volume

   • Blood pressure

2. Hypoaldosteronism: Defective synthesis/release of renin, angiotensin, aldosterone

Complications [zwp]

• Hyperkalemia --> arrhythmia

Epidemiology

Incidence per 100.000 [b9n][msy]

Approach

• Blood test: Na (hyponatremia), K (hyperkalemia), Aldosterone, 17 hydroxyprogesterone, 18 hydroxycorticosterone, plasma renin activity/concentration, Serum cortisol and plasma ACTH, creatinine

• Urine: Elevated urine Na ≥ 30 mmol/L, diminished urinary potassium, urine aldosterone

• Arterial bloodgas: pH (metabolic acidosis)

Treatment

1. Acute salt-wasting crisis: [zwp]

   • Volume and salt repletion with NaCl

   • Intravenous hydrocortisone in stress doses

2. Maintenance:

   • Mineralocorticoid replacement therapy: 9α-fluorocortisone 0.05-0.1 mg/day

   • Increased water and salt intake

Differential diagnoses

Adrenal insufficiency, Gordon syndrome, Liddle syndrome