Can a decreased mineralocorticoid (corticosteroid that regulates electrolyte and water balance) dosage in primary adrenal insufficiency cause impaired renal function (decreased estimated Glomerular Filtration Rate, eGFR)?

Can Decreased Mineralocorticoid Dosage Cause a Drop in eGFR in Primary Adrenal Insufficiency?

Yes, decreased mineralocorticoid dosage in primary adrenal insufficiency can cause a drop in eGFR through volume depletion and prerenal azotemia resulting from inadequate sodium retention and fluid balance.

Mechanism of Renal Impairment

Mineralocorticoid deficiency leads to prerenal renal failure through volume depletion. The physiologic mechanism is straightforward:

• Fludrocortisone acts on the distal renal tubules to enhance sodium reabsorption from tubular fluid into plasma, while increasing urinary excretion of potassium and hydrogen ions 1
• Inadequate mineralocorticoid replacement results in sodium wasting, volume depletion, and subsequent prerenal azotemia 2
• During acute adrenal crisis, typical laboratory findings include increased creatinine caused by prerenal renal failure, along with hyponatremia and hyperkalaemia 2

Clinical Manifestations of Mineralocorticoid Under-Replacement

Postural hypotension is the hallmark clinical sign of insufficient mineralocorticoid therapy. Key indicators include:

• Postural hypotension reflects insufficient mineralocorticoid therapy and/or low salt intake 2
• Clinical signs comprise hypotension, weakness, salt craving, and electrolyte disturbances (hyperkalemia, hyponatremia) 3
• Chronic under-replacement with mineralocorticoid is a recognized cause of recurrent adrenal crises 2

Evidence for Under-Replacement Being Common

Under-replacement of mineralocorticoids is frequently overlooked in clinical practice:

• Under-replacement of mineralocorticoids is common and possibly predisposes patients to recurrent adrenal crises 4
• Current replacement regimens may often be associated with mild hypovolemia 3
• Available data suggest that patients with PAI may be under-replaced with fludrocortisone, as symptoms indicating chronic mineralocorticoid under-replacement, such as salt craving and postural dizziness, persist in many treated patients 5
• Overreplacement with glucocorticoids often occurs as compensation for inadequate mineralocorticoid replacement 4

Monitoring and Prevention Strategy

To prevent eGFR decline from mineralocorticoid under-replacement, implement systematic monitoring:

• Measure blood pressure in supine and standing positions to detect postural hypotension 4, 6
• Monitor serum sodium, potassium, and creatinine levels regularly 2
• Assess plasma renin activity (PRA), aiming for the upper normal range 2, 4, 3
• Evaluate for clinical signs: salt craving, postural dizziness, weakness 3, 5

Dosing Considerations

Standard fludrocortisone dosing ranges from 50-200 μg daily, with higher doses sometimes needed:

• Fludrocortisone 50-200 μg (0.05-0.2 mg) daily is the standard replacement, usually taken as a single morning dose 4, 6
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during pregnancy 4, 6
• The mineralocorticoid activity of fludrocortisone is dose-dependent, with significant correlations between dose and sodium (positive), potassium (negative), and renin (negative) levels 7

Critical Pitfall to Avoid

Do not reduce fludrocortisone dose based solely on elevated PRA without considering clinical context. Important caveats:

• Optimal fludrocortisone replacement may be associated with mildly elevated plasma renin activity levels 8
• Attempted lowering of elevated PRA by raising fludrocortisone dose led to normalization of PRA but caused hypokalaemia and edema in some patients 8
• Patients should consume sodium salt and salty foods without restriction and avoid potassium-containing salts 4, 6

Special Clinical Scenarios

During acute illness or crisis, mineralocorticoid effects are temporarily provided by high-dose hydrocortisone:

• Mineralocorticoid replacement with fludrocortisone should be restarted when the hydrocortisone dose falls below 50 mg/day 2, 4
• Rapid intravenous administration of hydrocortisone (100 mg) saturates 11β-HSD type 2, thereby obtaining a desired mineralocorticoid effect during crisis 2