Is concurrent fludrocortisone (mineralocorticoid) necessary in patients receiving stress dose steroids (glucocorticoids)?

From the Guidelines

Concurrent fludrocortisone is generally not necessary when patients are receiving stress dose glucocorticoids, as the higher doses of glucocorticoids, such as hydrocortisone, provide sufficient mineralocorticoid activity to maintain fluid and electrolyte balance. This approach is supported by the understanding that hydrocortisone, a commonly used glucocorticoid for stress coverage, has inherent mineralocorticoid effects, especially at the higher doses utilized in stress dosing regimens 1.

When considering the management of patients with primary adrenal insufficiency (PAI), the guidelines suggest that most patients should take 15–25 mg of hydrocortisone (HC) daily in split doses, and 50–200 µg of fludrocortisone as a single daily dose 1. However, during periods of stress, such as surgery or severe illness, the dose of hydrocortisone is significantly increased, which provides adequate mineralocorticoid activity, potentially obviating the need for additional fludrocortisone.

Key points to consider include:

• The primary goal of stress dosing glucocorticoids is to prevent adrenal crisis by providing adequate glucocorticoid coverage during physiologic stress.
• Hydrocortisone has inherent mineralocorticoid activity, which is sufficient at stress doses to maintain fluid and electrolyte balance.
• For patients on chronic fludrocortisone, it is reasonable to continue their usual dose during stress dosing of glucocorticoids.
• Consideration of fludrocortisone supplementation may be necessary if using glucocorticoids with minimal mineralocorticoid activity, such as dexamethasone or methylprednisolone, especially for prolonged therapy.

In clinical practice, the decision to use concurrent fludrocortisone with stress dose glucocorticoids should be individualized, taking into account the specific patient's condition, the type and dose of glucocorticoid used, and the duration of therapy 1.

From the Research

Concurrent Fludrocortisone in Stress Dose Steroids

• The necessity of concurrent fludrocortisone (mineralocorticoid) in patients receiving stress dose steroids (glucocorticoids) is a topic of interest in the management of adrenal insufficiency.
• According to 2, patients with adrenal insufficiency are at risk of adrenal crisis, usually precipitated by major stress, such as severe infection or surgery, and early dose adjustments are required to cover the increased glucocorticoid demand in stress.
• However, the use of fludrocortisone in stress dose steroids is not explicitly mentioned in 2, but it is stated that fludrocortisone 0.05-0.2 mg/day is given for substitution in mineralocorticoid deficiency aiming at normotension, normokalaemia, and a plasma renin activity in the upper normal range.

Mineralocorticoid Activity and Stress

• A study published in 3 explored the dose of fludrocortisone treatment and its relationship with glucocorticoid therapy, sodium, potassium, renin, and clinical parameters in patients with primary adrenal insufficiency.
• The results showed that the mineralocorticoid activity of fludrocortisone was dose-dependent, and an overall reduction in the fludrocortisone dose was observed at the last follow-up visit in the group with longer follow-up.
• Another study 4 discussed mineralocorticoid substitution and monitoring in primary adrenal insufficiency, stating that patients usually show pronounced impairment of aldosterone secretion and require mineralocorticoid replacement for full recovery.

Stress Dose Steroids and Adrenal Crisis

• 5 investigated the prevention of adrenal crisis by comparing cortisol responses to major stress with stress dose hydrocortisone delivery, concluding that continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.
• However, the study did not specifically address the use of concurrent fludrocortisone in stress dose steroids.
• 6 discussed adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia, emphasizing the importance of increasing glucocorticoid doses during acute stress to prevent adrenal crisis.