Should a patient with adrenal insufficiency on hydrocortisone (cortisol replacement) who is started on dexamethasone (glucocorticoid) for a brain tumor and is undergoing surgery continue hydrocortisone and receive stress-dose adjustments?

From the Guidelines

For a patient with adrenal insufficiency on hydrocortisone who is started on dexamethasone for a brain tumor and is going for surgery, the hydrocortisone should be continued alongside dexamethasone, and the hydrocortisone dose should be increased to stress dosing for the perioperative period, as recommended by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.

Rationale

The rationale behind continuing hydrocortisone alongside dexamethasone is that they serve different purposes: dexamethasone primarily reduces brain edema around the tumor with minimal mineralocorticoid effect, while hydrocortisone provides both glucocorticoid and mineralocorticoid effects necessary for stress response and electrolyte balance. Patients with adrenal insufficiency cannot mount an appropriate cortisol stress response and are at risk for adrenal crisis during surgery if adequate coverage is not provided.

Stress Dosing

Typically, stress dosing for the perioperative period involves administering 100 mg of hydrocortisone intravenously before surgery, followed by a continuous infusion of hydrocortisone at 200 mg/24h, as recommended in the guidelines 1. After the immediate perioperative period, the patient can return to their maintenance hydrocortisone dose while continuing the prescribed dexamethasone regimen for the brain tumor.

Key Considerations

• Patients with primary adrenal insufficiency are more vulnerable to adrenal crisis and require careful management of their glucocorticoid and mineralocorticoid replacement therapy.
• Dexamethasone has no mineralocorticoid activity and is inadequate as glucocorticoid stress cover in patients with primary adrenal insufficiency.
• The plasma elimination half-time of exogenously administered hydrocortisone is approximately 90 minutes, and the volume of distribution of cortisol/hydrocortisone may be increased in critically ill patients.
• Hydrocortisone should be administered parenterally in the perioperative period until normal enteral function returns.

Recommendations

• Continue hydrocortisone alongside dexamethasone for patients with adrenal insufficiency undergoing surgery.
• Increase hydrocortisone dose to stress dosing for the perioperative period, typically 100 mg intravenously before surgery, followed by a continuous infusion of hydrocortisone at 200 mg/24h.
• Resume enteral hydrocortisone at double the pre-surgical therapeutic dose for 48 hours or for up to a week following major surgery.
• Monitor patients closely for signs of adrenal crisis and adjust glucocorticoid dosing as needed.

From the FDA Drug Label

In patients on corticosteroid therapy subjected to any unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving steroids already, dosage may have to be increased.

The patient with adrenal insufficiency on hydrocortisone (cortisol replacement) who is started on dexamethasone (glucocorticoid) for a brain tumor and is undergoing surgery should continue hydrocortisone and receive stress-dose adjustments of hydrocortisone, as the patient is already on steroid therapy and is being subjected to the stress of surgery 2.

From the Research

Adrenal Insufficiency and Glucocorticoid Replacement Therapy

• Patients with adrenal insufficiency require glucocorticoid replacement therapy, which can be affected by the introduction of other glucocorticoids like dexamethasone 3.
• The current standard treatment regimen for adrenal insufficiency involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone 4.

Perioperative Glucocorticoid Therapy

• Perioperative glucocorticoid therapy for patients with adrenal insufficiency is crucial to prevent adrenal crisis during stress periods like surgery 5, 6.
• A study found that lower doses of hydrocortisone can be safely administered to patients with adrenal insufficiency undergoing major surgery, as cortisol pharmacokinetics are altered in the postoperative period 5.

Dexamethasone and Hydrocortisone

• Dexamethasone is known to suppress the hypothalamic-pituitary-adrenal axis, with maximal cortisol suppression occurring approximately 24 hours post-dose 3.
• Patients on hydrocortisone for adrenal insufficiency who are started on dexamethasone may require adjustments to their glucocorticoid replacement therapy to avoid over- or under-treatment 4, 7.

Management of Glucocorticoid Replacement Therapy

• The management of glucocorticoid replacement therapy should take into account the individual patient's needs, including the risk of glucocorticoid-induced adrenal insufficiency and the need for stress-dose adjustments during surgery or other stress periods 6, 7.
• A careful approach to glucocorticoid tapering and patient counseling is necessary to assure a successful taper and prevent glucocorticoid withdrawal syndrome 7.