What is the significance of an elevated morning cortisol level after discontinuing prolonged prednisone (corticosteroid) therapy?

From the Guidelines

An elevated a.m. cortisol level after coming off prolonged prednisone therapy is a positive indicator of the recovery of the hypothalamic-pituitary-adrenal (HPA) axis, suggesting the adrenal glands have regained their natural cortisol production ability. This is crucial because prolonged use of prednisone or equivalent corticosteroids suppresses the body's own cortisol production, necessitating a recovery period after discontinuation. The significance of an elevated morning cortisol in this context is that it points towards the adrenal glands' ability to produce cortisol independently again, reducing the risk of adrenal insufficiency and its associated symptoms such as fatigue, weakness, and hypotension 1.

When interpreting the significance of an elevated a.m. cortisol, it's essential to consider the timing and the patient's recent history with corticosteroids. As noted in guidelines for managing immune-related adverse events, laboratory confirmation of adrenal insufficiency should not be attempted in patients given high-dose corticosteroids until treatment is ready to be discontinued, and even then, hydrocortisone needs to be held for 24 hours before endogenous function is assessed 1.

Key considerations in the management and interpretation of cortisol levels after prednisone therapy include:

• The need for education on stress dosing for sick days and the use of emergency steroid injectables to prevent adrenal crisis.
• The importance of medical alert bracelets for adrenal insufficiency.
• The potential for isolated central adrenal insufficiency with a low ACTH in patients treated with corticosteroids for other immune-related adverse events.
• The recommendation to test for recovery of the HPA axis after 3 months of maintenance therapy with hydrocortisone in patients with a history of corticosteroid treatment and no other central hormone deficiencies 1.

In clinical practice, the return of normal or elevated morning cortisol levels is a reassuring sign, but complete recovery and the safety of discontinuing supplemental steroids should be confirmed, especially after long-term or high-dose steroid use, ideally with an ACTH stimulation test. Consulting endocrinology for personalized recovery and weaning protocols using hydrocortisone is advisable for patients exhibiting symptoms of adrenal insufficiency after weaning off corticosteroids 1.

From the FDA Drug Label

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 significance of an elevated a.m. cortisol after coming off of prolonged prednisone therapy is that it may indicate recovery of the hypothalamic-pituitary-adrenal (HPA) axis.

• An elevated a.m. cortisol level suggests that the adrenal cortex is producing cortisol again, which is a good sign.
• However, it is essential to note that adrenocortical insufficiency can persist for up to 12 months after discontinuation of prednisone therapy, especially if the patient was on high doses for an extended period.
• In situations of stress, hormone therapy may need to be reinstituted to support the patient's adrenal function 2.

From the Research

Significance of Elevated a.m. Cortisol after Prolonged Prednisone Therapy

• The significance of an elevated a.m. cortisol level after coming off prolonged prednisone therapy is not directly addressed in the provided studies 3, 4, 5, 6, 7.
• However, it is known that prolonged use of glucocorticoids like prednisone can suppress the body's natural production of cortisol, leading to adrenal insufficiency 3, 4.
• After stopping prednisone therapy, the body may take some time to recover its natural cortisol production, and an elevated a.m. cortisol level could be a sign of this recovery process.
• It is also possible that an elevated a.m. cortisol level could be a sign of other underlying conditions, such as Cushing's syndrome or adrenal hyperplasia, although this is not directly related to the use of prednisone 5, 6.
• Further research is needed to fully understand the significance of an elevated a.m. cortisol level after prolonged prednisone therapy, as the current evidence does not provide a clear answer 7.

Adrenal Insufficiency and Cortisol Replacement

• Adrenal insufficiency is a condition where the body does not produce enough cortisol, and it can be caused by prolonged use of glucocorticoids like prednisone 3, 4.
• Cortisol replacement therapy is commonly used to treat adrenal insufficiency, and it involves taking synthetic cortisol-like medications to replace the body's natural cortisol production 4, 5.
• The goal of cortisol replacement therapy is to mimic the body's natural cortisol rhythm, and different medications and dosing regimens are being developed to achieve this goal 4, 5.
• However, the optimal approach to cortisol replacement therapy is still a topic of debate, and further research is needed to determine the best strategies for managing adrenal insufficiency 6, 7.