What are the risks of stopping prednisone (corticosteroid) abruptly and how can adrenal insufficiency be prevented?

From the Guidelines

Abruptly stopping prednisone or other corticosteroids is dangerous and should be avoided, as it can lead to adrenal insufficiency, a potentially life-threatening condition. Instead, these medications should always be tapered gradually under medical supervision. Sudden discontinuation of prednisone can lead to adrenal insufficiency, which occurs because long-term corticosteroid use suppresses the body's natural production of cortisol, leaving the adrenal glands temporarily unable to produce adequate amounts when the medication is withdrawn. This can result in serious symptoms including extreme fatigue, weakness, dizziness, nausea, vomiting, low blood pressure, hypoglycemia, and in severe cases, adrenal crisis—a life-threatening emergency.

Key Considerations

• The risk of adrenal insufficiency cannot be excluded by alternate day GC therapy and remains difficult to predict, as stated in the study by Duru et al. 1.
• To prevent adrenal insufficiency, patients should follow a carefully planned tapering schedule, typically reducing the dose by small amounts (often 2.5-5mg) every 1-2 weeks, with slower reductions at lower doses, as recommended by the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults 1.
• The exact tapering schedule depends on the original dose, duration of treatment, and individual patient factors.
• During times of illness, injury, or stress, patients who are tapering or have recently completed a taper may need temporary increases in their corticosteroid dose, as these situations demand more cortisol than their recovering adrenal glands can produce.
• Patients should wear medical alert identification and carry information about their corticosteroid use to ensure proper emergency treatment if needed, as suggested by the guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency 1.

Patient Education

• Patients need education on stress dosing for sick days, use of emergency steroid injectables, when to seek medical attention for impending adrenal crisis, and a medical alert bracelet for adrenal insufficiency to trigger stress dose corticosteroids by EMS, as recommended by the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update 1.
• Patients should be informed about the risks of adrenal insufficiency and how to prevent it, including the importance of gradual tapering and stress dosing, as stated in the study by Duru et al. 1.

From the FDA Drug Label

Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. Adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly

The risks of stopping prednisone abruptly include adrenal insufficiency, which can be minimized by gradual reduction of dosage. To prevent adrenal insufficiency, it is recommended to:

• Withdraw prednisone gradually rather than abruptly
• Monitor the patient's condition closely during the withdrawal process
• Be aware that adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids 2
• Consider increasing the dosage of prednisone in situations of stress during the withdrawal period 2
• Note that relative insufficiency may persist for up to 12 months after discontinuation of therapy, and hormone therapy should be reinstituted in any situation of stress occurring during that period 2

From the Research

Risks of Stopping Prednisone Abruptly

• Stopping prednisone abruptly can lead to adrenal insufficiency, a life-threatening condition where the adrenal glands do not produce enough cortisol 3.
• Adrenal insufficiency can occur in patients who have been taking prednisone for a long time, especially those who have been taking high doses or have been taking it for more than 5 months 4, 5.
• The risk of adrenal insufficiency is related to the duration and cumulative dose of prednisone therapy 4.

Preventing Adrenal Insufficiency

• To prevent adrenal insufficiency, patients who are stopping prednisone should be gradually tapered off the medication to allow the adrenal glands to recover 4, 5.
• A short Synacthen test can be used to evaluate adrenal function and determine if a patient is at risk of adrenal insufficiency 4, 5.
• Patients who are found to have adrenal insufficiency may need to take hydrocortisone replacement therapy to manage their condition 5, 3.

Management of Adrenal Insufficiency

• Adrenal insufficiency can be managed with hydrocortisone replacement therapy, which should be taken in doses that mimic the natural production of cortisol by the adrenal glands 3.
• Patients with adrenal insufficiency should also be educated on how to manage their condition, including how to increase their hydrocortisone dose during times of stress or illness 3.
• Glucocorticoid emergency kits can be prescribed to patients with adrenal insufficiency to help manage acute adrenal crises 3.

Mortality Risk

• Patients with adrenal insufficiency who are taking prednisolone may have a higher mortality risk compared to those taking hydrocortisone, especially in primary adrenal insufficiency 6.
• However, more research is needed to confirm this finding and to determine the long-term safety of prednisolone as a replacement therapy for adrenal insufficiency 6.