Will prednisone (corticosteroid) suppress morning cortisol levels?

From the Guidelines

Yes, prednisone will suppress morning cortisol levels. Prednisone is a synthetic glucocorticoid that mimics the effects of cortisol in the body, and when taken regularly, it signals the body to reduce its own natural cortisol production through negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. This suppression can occur with doses as low as 5 mg daily when taken for more than a few weeks, as supported by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.

Key Considerations

• The effect is most pronounced when prednisone is taken in the evening, as it interferes with the natural cortisol peak that typically occurs in early morning hours.
• For patients on long-term prednisone therapy (generally more than 3 weeks), this suppression can lead to adrenal insufficiency if the medication is stopped abruptly.
• Therefore, prednisone should be tapered gradually when discontinuing treatment to allow the adrenal glands time to resume normal cortisol production, as advised in the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.
• Patients should be aware that during periods of stress, illness, or surgery, they may need supplemental steroids if they've been on long-term prednisone therapy, as their bodies may not produce enough cortisol to meet increased demands.

Clinical Implications

• It is crucial for clinicians to be aware of the potential for adrenal insufficiency in patients on long-term prednisone therapy and to manage them appropriately, including gradual tapering of the medication and supplemental steroids during periods of stress.
• The guidelines also emphasize the importance of starting corticosteroids first when planning hormone replacement therapy for multiple deficiencies to prevent precipitating adrenal crisis, as noted in the American Society of Clinical Oncology clinical practice guideline 1.
• Furthermore, patients should be educated on stress dosing for sick days, the use of emergency steroid injectables, and when to seek medical attention for impending adrenal crisis, as recommended in the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.

From the FDA Drug Label

Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm Serum levels of ACTH rise from a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am. During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenocortical suppression for 11/4; to 11/2; days following a single dose)

Yes, prednisone will suppress morning cortisol. The drug label states that during conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited, which leads to subsequent suppression of cortisol production by the adrenal cortex. Additionally, it is mentioned that prednisone is considered a short-acting corticosteroid that can produce adrenocortical suppression for 1 1/4 to 1 1/2 days following a single dose 2.

From the Research

Morning Cortisol Suppression by Prednisone

• The effect of prednisone on morning cortisol levels is not directly addressed in the provided studies 3, 4, 5, 6, 7.
• However, it is known that glucocorticoids like prednisone can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to decreased cortisol production 3, 4, 5, 6, 7.
• Studies have established various morning cortisol cutoff values to predict adrenal insufficiency or sufficiency, but these values may not apply to patients taking prednisone due to its suppressive effect on cortisol production 3, 4, 5, 6, 7.
• For example, a study found that a morning serum cortisol level of >236 nmol/l predicted adrenal sufficiency with sensitivity 84% and specificity 71% 3, but this cutoff value may not be valid for patients taking prednisone.
• Another study suggested that a mean basal morning serum cortisol of >300 nmol/L excluded the possibility of adrenal insufficiency, and a level of <110 nmol/L suggested adrenal insufficiency 4, but again, this may not apply to patients taking prednisone.
• A more recent study found that morning serum cortisol cutoff values of <3.65, <2.35, and <1.5 mcg/dL had specificity of 98%, 99%, and 100%, respectively, for confirming adrenal insufficiency, while cutoff values of >12.35, >14.2, and >14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, for excluding adrenal insufficiency 6, but the effect of prednisone on these cutoff values is unknown.
• In patients with suspected central adrenal insufficiency, a morning serum cortisol cutoff of ≤323.3 nmol/L had a sensitivity of 87.7% and specificity of 46.1% for predicting a deficient response to insulin tolerance test, while a cutoff of ≤126.4 nmol/L had a sensitivity of 13.8% and specificity of 98.7% 7, but the impact of prednisone on these cutoff values is not clear.