Hypoaldosteronism medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2] Akshun Kalia M.B.B.S.[3]

The mainstay of treatment for hypoaldosteronism depends upon the level of plasma potassium. Prompt ECG is advised in all patients suspected of hypoaldosteronism as hyperkalemia may lead to cardiac conduction defects and life threatening arrhythmias. Patients with no ECG changes and moderate hyperkalemia (6.5–7.5 mmol/l) require only monitoring. Patients with severe hyperkalemia (>7.5 mmol/l) are treated with emergency measures for hyperkalemia (calcium, insulin, β₂ agonist or cation resins) and fludrocortisone. Depending upon the volume status, patients may be treated with either 0.9% normal saline (hypovolemia) or furosemide (hypervolemic).

Medical therapy for hypoaldosteronism depends upon the age of the patient and other concurrent disorders such as diabetic nephropathy and renal insufficiency. Medical therapy includes: ^[1][2][3]

• Prompt ECG must be obtained in all suspected patients of hypoaldosteronism as hyperkalemia may alter the electrical activity of heart and predispose to life threatening arrhythmias.
• Patients with no ECG changes and moderate hyperkalemia (6.5–7.5 mmol/l) require only monitoring potassium concentrations.
  • Drugs promoting hyperkalemia should be avoided, such as β blockers, ACE inhibitor, angiotensin receptor blockers and potassium-sparing diuretics.
  • Reduced dietary intake of potassium.
• Patients with severe hyperkalemia (>7.5 mmol/l) are treated with emergency measures for hyperkalemia as necessary (see below) and fludrocortisone 0.05 to 0.1 mg PO q24h.
• Depending upon the volume status, patients may be treated with:
  • In hypovolemic patients, normal saline 0.9% is given to restore volume status.
  • In hypervolemic patients (signs of volume overload) or underlying heart failure, furosemide 20 to 40 mg q24h is given.

1. Management of Hyperkalemia

• 1.1 Calcium supplementation
  • Preferred regimen (1): Calcium gluconate 10% (10ml)

  Note: Usually infused through a central venous catheter as the calcium may cause phlebitis and does not lower potassium but decreases myocardial excitability, protecting against life threatening arrhythmias.

• 1.2 Insulin
  • Preferred regimen (1): Short acting insulin (e.g. Actrapid) 10-15 u IV along with 50 ml of 50% dextrose (to prevent hypoglycemia)

  Note: Short acting Insulin leads to a shift of potassium ions into cells, secondary to increased activity of the sodium-potassium ATPase.

• 1.3 Bicarbonate therapy
  • Preferred regimen (1): Sodium bicarbonate 1 ampule (45mEq) infused over 5 minutes is effective in cases of metabolic acidosis.

  Note:The bicarbonate ion will stimulate an exchange of cellular H⁺ for Na⁺, thus leading to stimulation of the sodium-potassium ATPase.

• 1.4 β₂-selective agonist
  • Preferred regimen (1): Salbutamol nebulization (e.g. 10-20 mg)
  • Preferred regimen (2): (Albuterol, Ventolin^®) nebulization (e.g. 10-20 mg)

  Note: This drug promotes movement of potassium into cells, lowering the blood levels.

• 1.5 Potassium binding resins
  • Preferred regimen (1): Polystyrene sulfonate (calcium resonium, kayexalate) is a binding resin that binds potassium within the intestine and removes it from the body by defecation.
  • Preferred regimen (2): Calcium resonium (15g three times a day in water) can be given by mouth.
  • Preferred regimen (3): Kayexalate can be given by mouth or as an enema. In both cases, the resin absorbs potassium within the intestine and carries it out of the body by defecation.
  • Preferred regimen (4): Patiromer anion

  Note (1): Kayexalate may cause diarrhea.

  Note (2): Refractory or severe cases may need dialysis to remove the potassium from the circulation.

  Note (3): Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal of an offending medication, and/or the addition of a diuretic (such as furosemide (Lasix^®) or hydrochlorothiazide).

  Note (4): Patiromer anion is a potassium binding ion cation exchange polymer that increases the gastrointestinal excretion of potassium (it is available in 8.4, 16.8, and 25.2 grams of powder in packets to be administered once daily).

  Note (5): Patiromer should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

2. Management on the basis of subtype of hypoaldosteronism

• 2.1 Hyporeninemic Hypoaldosteronism: Treatment is aimed at normalizing volume status, plasma potassium and aldosterone levels.^[4][5][6]
  • 2.1.1 Thiazide diuretics:
    • Preferred regimen (1): furosemide 20 to 40 mg 24h

    Note: Diuretics are the first-line therapy for patients with severe hyperkalemia (>7.5 mmol/l) and fluid overload (seen in renal impairment or congestive heart failure). Avoid diuretics in patients with signs of hypotension or volume depletion.

  • 2.1.2 Patients who are unable to tolerate diuretics due to underlying hypotension or volume depletion are treated with:
    • Preferred regimen (1): Sodium bicarbonate (NaHCO3)

    Note: Sodium bicarbonate (NaHCO3) is the second line therapy and used in patients with ‘normal renal function and who cannot tolerate diuretics‘ due to underlying hypotension or volume depletion. In these patients sodium bicarbonate (NaHCO3) can be used to increase distal delivery of bicarbonate anion and increase urinary potassium excretion. Sodium bicarbonate (NaHCO3) also corrects underlying metabolic acidosis.

    • Preferred regimen (2): Sodium polystyrene sulfonate

    Note: Sodium polystyrene sulfonate is used in patients with inadequate renal function and decreased potassium excretion. 1 gm of sodium polystyrene sulfonate can remove upto 1 mEq of potassium.

  • 2.1.3 Aldosterone analogues:
    • Preferred regimen (1): fludrocortisone 0.1-0.3 mg q24h

    Note: Aldosterone analogues such as fludrocortisone in the dose of 0.1-0.3 mg q24h are the third line therapy .

• 2.2 Hyperreninemic hypoaldosteronism: Secondary isolated hypoaldosteronism also known as hyperreninemic hypoaldosteronism is seen in patients with severe underlying illness such as liver cirrhosis or heart failure.^[7]
  • 2.2.1: The primary focus of the treatment in hyperreninemic hypoaldosteronism is to treat the underlying condition.
  • 2.2.2: Decreased level of aldosterone in patients of hyperreninemic hypoaldosteronism does not lead to any clinical complications and is therefore seldom treated.

• 2.3 Isolated hypoaldosteronism:^[8]
  • 2.3.1 Aldosterone analogues:

    Preferred regime (1): 9α-fludrocortisone 0.05 to 0.2 mg q24h

    Note (1): Isolated hypoaldosteronism from CYP11B2 gene mutation presents in infancy and are treated with 9α-fludrocortisone.

    Note (2): In adults treatment is not necessary.^[8]

• 2.4 Pseudohypoaldosteronism type I: Patients of pseudohypoaldosteronism are resistant to aldosterone or mineralocorticoid therapy and treatment is based on:^[9]
  • Correcting the underlying electrolyte abnormalities with sodium chloride (2 to 8 g q24h) and cation-exchange resins such as sodium polystyrene sulfonate.
  • Thiazide diuretics are used to treat hyperkalemia. In patients with severe hyperkalemia (>7.5 mmol/l) peritoneal dialysis may also be done.
  • Pseudohypoaldosteronism decreases after few years and the therapy may be discontinued. However, these patients require salt supplementation till first 3-4 years of life.

• 2.5 Primary or secondary adrenal insufficiency: These patients are treated with fludrocortisone and cortisol:^[10]
  • 2.5.1 Fludrocortisone:
    • Preferred regimen (1): fludrocortisone 0.1 mg PO q24h.
      • Reduce dose to 0.05 mg q24h if transient hypertension develops.
      • Maintenance dosage range: 0.1 mg 3 times weekly to 0.2 mg q24h.
  • 2.5.2 Cortisone or hydrocortisone:
    • Preferred regimen (1): Cortisone 10 to 37.5 mg q12h orally given in 2 divided doses with two-thirds of the total dose given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.).

For complete therapy in adrenal insufficiency please click here.

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