Does glucocorticoid (corticosteroid) therapy increase water and sodium retention?

From the Guidelines

Glucocorticoids do not primarily increase water and sodium retention; this effect is mainly attributed to mineralocorticoids like aldosterone. The primary function of glucocorticoids, such as cortisol, prednisone, and dexamethasone, is to regulate metabolism, immune function, and stress responses, with minimal direct effect on sodium and water balance at physiological doses 1. In contrast, mineralocorticoids act on the distal tubules and collecting ducts of the kidneys to increase sodium reabsorption and potassium excretion, leading to water retention. This is evident in the use of mineralocorticoid receptor antagonists, such as spironolactone, in the treatment of heart failure, where they have been shown to reduce hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF) 1. The distinction between glucocorticoids and mineralocorticoids is crucial, as it explains why patients on glucocorticoid therapy do not typically develop significant fluid retention unless they are receiving very high doses or have underlying conditions affecting fluid balance.

Some key points to consider:

• Glucocorticoids have a minimal direct effect on sodium and water balance at physiological doses.
• Mineralocorticoids, such as aldosterone, play a primary role in regulating sodium and water balance.
• The use of mineralocorticoid receptor antagonists, like spironolactone, can help reduce hospitalizations in patients with HFpEF.
• Patients on glucocorticoid therapy may develop fluid retention at supraphysiological doses or with underlying conditions affecting fluid balance.

It is essential to understand the differences between glucocorticoids and mineralocorticoids to provide appropriate treatment and management for patients with various conditions, including heart failure and adrenal hormone excess disorders.

From the FDA Drug Label

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium.

Yes, glucocorticoids can increase water and sodium retention. This effect is more likely to occur with average and large doses of glucocorticoids like hydrocortisone or cortisone, and less likely with synthetic derivatives except when used in large doses 2, 3.

• Dietary salt restriction and potassium supplementation may be necessary to mitigate these effects.
• The use of glucocorticoids can lead to elevation of blood pressure and increased excretion of potassium in addition to water and sodium retention.

From the Research

Glucocorticoid Effects on Water and Sodium Retention

• The effect of glucocorticoids on water and sodium retention is complex and involves multiple mechanisms 4, 5, 6.
• Glucocorticoids can increase water and sodium excretion, rather than retention, as shown in a study where dexamethasone treatment increased water and sodium excretion without affecting water intake 4.
• However, glucocorticoids can also stimulate renal Na+ transport, which can lead to sodium retention, particularly during moderate excess 6.
• The mineralocorticoid receptor plays a crucial role in regulating sodium retention, and glucocorticoids can occupy this receptor, leading to increased sodium retention 5, 6.
• The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protects the mineralocorticoid receptor from glucocorticoid occupation, but its saturability can be achieved at high-normal physiological plasma cortisol levels, leading to overstimulation of the receptor by cortisol 5.

Implications for Hypertension and Hyponatremia

• Glucocorticoid-induced hypertension is a major concern, and the mechanism involves overstimulation of the mineralocorticoid receptor, leading to renal Na+ retention and volume expansion 5, 6.
• Hyponatremia management is also affected by glucocorticoids, which can influence water balance through their effects on arginine vasopressin secretion and peripheral effects on hemodynamics and renal water handling 7.
• The complex interplay between glucocorticoids and water balance has implications for pituitary surgery and the management of hyponatremia 7.

Receptor-Mediated Actions

• Glucocorticoids and mineralocorticoids exert their effects through intracellular receptor molecules, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) 8.
• Natural inactivating mutations of the GR or MR genes can lead to significant clinical phenotypes, including glucocorticoid resistance and pseudohypoaldosteronism type 1 8.
• The biological relevance of the GR and MR receptors has been confirmed in mice with inactivated or modified genes, and natural compensated glucocorticoid and/or mineralocorticoid 'resistance' has been described in several mammalian species 8.