Can an adrenocorticotropic hormone (ACTH) stimulating test be performed while on hydrocortisone (cortisol) therapy?

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From the Guidelines

You should not perform an adrenocorticotropic hormone (ACTH) stimulating test while on hydrocortisone (cortisol) therapy, as it can lead to false-negative results and inaccurate interpretation. The ACTH stimulation test measures how well your adrenal glands respond to adrenocorticotropic hormone by producing cortisol, and taking hydrocortisone before the test will artificially elevate cortisol levels in your bloodstream, masking any potential adrenal insufficiency 1.

To ensure accurate results, hydrocortisone needs to be held for at least 24 hours before the test, as the measurement of therapeutic steroids in the assay for cortisol varies 1. Other steroids may need to be held for longer periods before endogenous function is assessed. It is essential to consult endocrinology for recovery and weaning protocols using hydrocortisone in patients with symptoms of adrenal insufficiency after weaning off corticosteroids 1.

Some key considerations when planning to perform an ACTH stimulation test include:

  • The need to start corticosteroids first when planning hormone replacement therapy for multiple deficiencies, as other hormones can accelerate the clearance of cortisol and precipitate adrenal crisis 1
  • The potential for false-negative results early in hypophysitis, as adrenal reserve declines slowly after pituitary stimulation is lost 1
  • 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 1

In patients with adrenal insufficiency, a recent history of treatment with corticosteroids, and no other central hormone deficiencies, the HPA axis should be tested for recovery after 3 months of maintenance therapy with hydrocortisone 1. 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 1.

From the Research

Adrenocorticotropic Hormone (ACTH) Stimulating Test on Hydrocortisone Therapy

  • The ACTH stimulating test can be performed while on hydrocortisone (cortisol) therapy, but the interpretation of the results may be affected by the therapy 2.
  • A study suggests that the ACTH-ST may be used for the diagnosis of suspected adrenal insufficiency within the first 3 days after initiation of empiric glucocorticoid therapy 2.
  • However, another study notes that the outcome of an ACTH test is not always an appropriate indicator of the need for glucocorticosteroid replacement, particularly in cases of partial ACTH deficiency 3, 4.
  • The rapid ACTH stimulation test (RST) and the prolonged ACTH stimulation test (PST) have been standardized, and the post-ACTH cortisol value is the single parameter chosen to interpret both tests 5.
  • Hydrocortisone administration can suppress plasma ACTH levels, and a significant fall in blood glucose levels was found in adrenalectomized patients after hydrocortisone injection 6.

Key Considerations

  • The timing of the ACTH test after initiation of hydrocortisone therapy is crucial, as the serum cortisol response may be compromised after 72 hours 2.
  • The interpretation of the ACTH test results should take into account the clinical context and the potential for misleading results, particularly in cases of incomplete ACTH deficiency states 4.
  • Further studies are needed to confirm the initial results and to establish clear guidelines for the use of the ACTH test in patients on hydrocortisone therapy 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adrenocorticotropic hormone stimulation test during high-dose glucocorticoid therapy.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2009

Research

Problems in Interpretation of the short ACTH test: an update and historical notes.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2015

Research

Effect of hydrocortisone on ACTH, growth hormone, insulin and glucose in the blood of bilaterally adrenalectomized patients.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 1980

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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