How long after discontinuing prednisone (corticosteroid) should one wait to check cortisol levels?

From the Guidelines

To accurately check cortisol levels after prednisone use, it is recommended to wait at least 3 months after discontinuing the medication, especially if you have been on high-dose or long-term therapy, as this allows for the recovery of the hypothalamic-pituitary-adrenal (HPA) axis and provides a more accurate assessment of endogenous cortisol production. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of waiting for an adequate period before assessing cortisol levels to avoid false-negative results 1. The study highlights that laboratory confirmation of adrenal insufficiency should not be attempted in patients given high-dose corticosteroids for other immune-related adverse events until treatment is ready to be discontinued. Furthermore, it is essential to consider consulting endocrinology for recovery and weaning protocols using hydrocortisone in patients with symptoms of adrenal insufficiency after weaning off corticosteroids.

Some key points to consider when checking cortisol levels after prednisone use include:

• The need to hold hydrocortisone for 24 hours and other steroids for longer before endogenous function is assessed
• The importance of educating patients on stress dosing for sick days, use of emergency steroid injectables, and when to seek medical attention for impending adrenal crisis
• The recommendation to test for recovery of the HPA axis after 3 months of maintenance therapy with hydrocortisone in patients with adrenal insufficiency and a recent history of treatment with corticosteroids
• The potential for isolated central adrenal insufficiency with a low ACTH in patients treated with corticosteroids for other immune-related adverse events.

It is crucial to prioritize the patient's safety and well-being by consulting with their healthcare provider before stopping prednisone and following a specific tapering schedule and optimal timing for cortisol testing based on their individual medical situation 1.

From the FDA Drug Label

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 up to 12 months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy following large doses for prolonged periods; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.

The time to check cortisol levels after stopping prednisone is not explicitly stated in the provided drug labels. However, it is mentioned that adrenocortical insufficiency may persist for up to 12 months after discontinuation of therapy.

• It is recommended to reinstitute hormone therapy in situations of stress during this period.
• Gradual reduction of dosage is advised to minimize the risk of adrenocortical insufficiency. 2 2

From the Research

Cortisol Levels After Prednisone Withdrawal

• The time it takes for cortisol levels to return to normal after prednisone withdrawal can vary depending on the duration and dose of prednisone treatment 3.
• A study found that 78% of patients had a blunted cortisol response to ACTH 2 days after corticosteroid withdrawal, which decreased to 33% after 7 and 21 days 3.
• Basal cortisol levels can be used to predict an impaired function of the HPA axis, with levels of > 400 and < 150 nmol/l being 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively 3.

Hypothalamic-Pituitary-Adrenal Axis Response

• The HPA axis response to the severity of illness in non-critically ill patients has been studied, and it was found that mild alterations in the HPA axis occurred depending on the severity of illness 4.
• Relative corticosteroid insufficiency was not confirmed in non-critically ill patients, and all patients had a good outcome without glucocorticoid treatment 4.
• The physiological basis for the etiology, diagnosis, and treatment of adrenal disorders, including Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia, has been reviewed 5.

Evaluation of the Hypothalamic-Pituitary-Adrenal Axis

• The HPA axis has been evaluated in patients with antiphospholipid syndrome, and it was found that patients with APS did not have HPA axis insufficiency 6.
• Partial adrenal insufficiency could not be excluded in two patients, and further longitudinal studies are needed to determine the significance of periodic evaluation of the HPA axis in patients with APS 6.
• A clinical approach to adrenal insufficiency in hospitalized patients has been reviewed, including various aetiologies and management of adrenal insufficiency 7.