Management of Hypoaldosteronism
Fludrocortisone 0.1 mg daily is the medication of choice for mineralocorticoid replacement in hypoaldosteronism, with doses ranging from 0.1 mg three times weekly to 0.2 mg daily depending on clinical response. 1
Diagnostic Confirmation Before Treatment
Before initiating therapy, confirm the diagnosis by demonstrating:
- Low plasma aldosterone concentration (typically <10 ng/dL) with elevated or inappropriately normal plasma renin activity 1
- Hyperkalemia (often >5.5 mEq/L) and/or hyperchloremic metabolic acidosis 2, 3
- Hyponatremia with urinary sodium wasting may also be present, particularly in volume-depleted states 4
The aldosterone-to-renin ratio (ARR) is used diagnostically, but in hypoaldosteronism the ratio will be low (opposite of hyperaldosteronism), with specificity improving when plasma renin activity exceeds 0.5 ng/mL/h 1. Confirmatory testing with saline infusion or oral salt loading may be performed if the diagnosis is uncertain 1.
Pharmacologic Management
First-Line Treatment: Fludrocortisone
Start fludrocortisone at 0.1 mg daily orally, which is the standard initial dose for mineralocorticoid replacement 1. This dose effectively reverses hyperkalemia and metabolic acidosis in most patients 2.
Dose titration:
- Increase to 0.2 mg daily if hyperkalemia or acidosis persists 1
- Some patients may require only 0.1 mg three times weekly for maintenance 1
- Adjust based on serum potassium, blood pressure, and clinical symptoms 5
Monitoring Requirements
Check serum electrolytes and blood pressure within 1 week of initiation and after each dose adjustment 5. Continue monitoring:
- Serum potassium and sodium at regular intervals to assess treatment adequacy 5
- Blood pressure at each visit, as fludrocortisone can induce sodium retention and hypertension 5, 2
- Signs of volume overload including edema, cardiac enlargement, or congestive heart failure 5
Managing Treatment-Related Adverse Effects
Hypertension and edema are the most common adverse effects due to mineralocorticoid-induced sodium and water retention 5. If these develop:
- Reduce fludrocortisone dose if blood pressure becomes elevated 2
- Consider adding loop diuretics (furosemide or bumetanide) to manage volume overload while maintaining potassium correction 2, 3
- Implement dietary sodium restriction 3
Hypokalemia can paradoxically develop with excessive fludrocortisone dosing 5. Monitor potassium levels and reduce the dose if this occurs 5.
Alternative and Adjunctive Therapies
When Fludrocortisone is Insufficient or Contraindicated
Loop diuretics (furosemide, bumetanide) can be used as alternatives or additives when fludrocortisone causes problematic sodium retention or hypertension 2, 3. These promote potassium excretion without the mineralocorticoid effects.
Sodium bicarbonate may be added to specifically address persistent metabolic acidosis 2, 3.
Potassium-binding resins (sodium polystyrene sulfonate) can be used acutely for severe hyperkalemia while awaiting fludrocortisone effect 3.
Dietary Modifications
Restrict dietary potassium intake as a general measure in all patients with hypoaldosteronism 2. This includes limiting high-potassium foods (bananas, oranges, potatoes, tomatoes, salt substitutes).
Liberalize sodium intake unless hypertension or volume overload develops, as these patients have impaired renal sodium conservation 2, 3.
Special Populations and Considerations
Elderly Patients
Exercise particular caution in elderly patients, who commonly have conditions exacerbated by fludrocortisone including hypertension, edema, congestive heart failure, cataracts, glaucoma, and osteoporosis 5. Start at the low end of the dosing range (0.1 mg daily or less) and monitor closely 5.
Elderly patients frequently take medications that interact with fludrocortisone, including digitalis glycosides (increased arrhythmia risk with hypokalemia), oral anticoagulants (decreased prothrombin time), and antidiabetic drugs (diminished effect) 5.
Patients with Renal Impairment
Hypoaldosteronism most commonly occurs in patients with mild to moderate renal dysfunction, particularly those with diabetic nephropathy, interstitial nephritis, or obstructive uropathy 2. These patients require especially careful monitoring as they are at higher risk for both hyperkalemia (from reduced renal potassium excretion) and treatment-related complications 2.
Pregnancy and Lactation
Fludrocortisone is FDA Pregnancy Category C - use only if clearly needed, as adequate human studies are lacking 5. Infants born to mothers receiving substantial doses should be carefully observed for signs of hypoadrenalism 5.
Fludrocortisone is excreted in breast milk - exercise caution when administering to nursing mothers 5.
Common Clinical Pitfalls
Do not confuse hypoaldosteronism with primary adrenal insufficiency (Addison's disease) - hypoaldosteronism is typically isolated mineralocorticoid deficiency without cortisol deficiency 4. Only 5% of hypoaldosteronism cases have concurrent primary adrenal insufficiency 4.
Do not overlook medication-induced hypoaldosteronism - prostaglandin inhibitors (NSAIDs), beta-blockers, ACE inhibitors, and ARBs can all contribute to or cause hypoaldosteronism 2. Review and discontinue offending agents when possible.
Do not ignore extrarenal causes of hyperkalemia - consider oral potassium intake, potassium-sparing diuretics, and intracellular-to-extracellular potassium shifts (particularly with insulin deficiency in diabetics) as contributing factors 2.
Do not rely solely on potassium levels to guide therapy - also monitor acid-base status, sodium balance, blood pressure, and volume status for comprehensive management 2, 3.