What is the likely cause of water retention in a patient with primary adrenal insufficiency taking 0.15mg mineralocorticoid (mineralcorticoid) and 20mg glucocorticoid (glucocorticoid)?

Water Retention in Primary Adrenal Insufficiency

The most likely cause of this patient's water retention is excessive glucocorticoid dosing (20mg daily), which is above the recommended replacement range and causing Cushing's syndrome-like effects including central obesity and peripheral edema. 1

Analysis of Current Replacement Therapy

Glucocorticoid Dosing Assessment

• The patient is receiving 20mg of glucocorticoid daily, which exceeds the recommended replacement range of 15-25mg for hydrocortisone (if this is hydrocortisone) or is dramatically excessive if this is prednisolone (recommended 4-5mg daily). 1

• Weight gain in the trunk and buttocks with peripheral edema below the knees is a classic pattern of glucocorticoid excess, not mineralocorticoid excess. 1

• The patient's weight increase from 140 to 150 lbs (approximately 7% gain) with this distribution pattern strongly suggests iatrogenic Cushing's syndrome from glucocorticoid over-replacement. 1

Mineralocorticoid Dosing Assessment

• The fludrocortisone dose of 0.15mg (150 µg) falls within the standard replacement range of 50-200 µg daily and is appropriate for this patient's size. 1, 2

• Mineralocorticoid excess typically causes hypertension and peripheral edema, but the distribution pattern described (trunk and buttocks fat accumulation) is not consistent with pure mineralocorticoid excess. 1

• Peripheral edema from fludrocortisone over-replacement would be expected to present with elevated blood pressure and would not explain the central fat distribution. 1

Clinical Evaluation Required

Immediate Assessment

• Check blood pressure in supine and standing positions to evaluate for hypertension (suggesting mineralocorticoid excess) versus normal/low blood pressure. 1

• Measure serum sodium and potassium - mineralocorticoid excess causes hypokalemia, while appropriate replacement maintains normal electrolytes. 1, 2

• Assess for other signs of glucocorticoid excess: moon facies, supraclavicular fat pads, easy bruising, proximal muscle weakness, and striae. 1

Distinguishing Features

• Glucocorticoid excess causes: central obesity (trunk, face, dorsocervical area), peripheral edema from capillary fragility, and relative limb sparing. 1

• Mineralocorticoid excess causes: generalized peripheral edema, hypertension, and hypokalemia without preferential central fat distribution. 1, 2

Management Recommendations

Primary Intervention

Reduce the glucocorticoid dose to the appropriate replacement range - if using hydrocortisone, reduce to 15-20mg daily in divided doses; if using prednisolone, reduce dramatically to 4-5mg daily. 1

Mineralocorticoid Adjustment

• If blood pressure is elevated and peripheral edema is present, consider reducing fludrocortisone to 0.1mg (100 µg) daily, but do not discontinue it as this would risk adrenal crisis. 1

• Monitor for signs of under-replacement including salt cravings, orthostatic hypotension, and hyperkalemia after any dose reduction. 1, 2

Important Caveats

• Under-replacement of mineralocorticoids is common and sometimes compensated for by over-replacement of glucocorticoids, which may be occurring in this patient. 1

• If essential hypertension develops, treat with a vasodilator rather than stopping mineralocorticoid replacement, though dose reduction should be considered. 1

• Avoid diuretics, NSAIDs, licorice, and grapefruit juice as these interact with fludrocortisone and may complicate management. 1, 2

Follow-up Monitoring

• Reassess weight, blood pressure, and edema pattern in 2-4 weeks after glucocorticoid dose adjustment. 1

• Recheck electrolytes to ensure appropriate mineralocorticoid replacement is maintained. 1, 2

• Measure plasma renin activity (PRA) if available, aiming for upper normal range to confirm adequate mineralocorticoid replacement. 2, 3