Is a short Synacthen (Synthetic Adrenocorticotropic Hormone) test necessary before long-term withdrawal of corticosteroids?

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Last updated: April 6, 2025 • View editorial policy

From the Guidelines

Before long-term withdrawal of steroids, a short Synacthen test is recommended to assess adrenal function, as it helps determine if the hypothalamic-pituitary-adrenal (HPA) axis has recovered sufficiently to produce adequate cortisol independently. This is particularly important for patients who have been on steroids for more than 1 month at a dose equivalent to prednisolone ≥ 5 mg, as their adrenal glands may have become suppressed due to negative feedback from exogenous steroids, potentially leading to adrenal crisis if steroids are withdrawn too quickly 1.

Key Considerations

  • The short Synacthen test involves measuring baseline cortisol levels, administering 250 micrograms of synthetic ACTH (Synacthen/cosyntropin) intravenously or intramuscularly, then measuring cortisol levels again after 30 and 60 minutes.
  • A normal response (cortisol level >500-550 nmol/L or >18-20 μg/dL) indicates adequate adrenal function and suggests steroids can be safely withdrawn.
  • If the test shows inadequate response, steroid withdrawal should proceed more cautiously with slower tapering to allow the HPA axis more time to recover.

Rationale

  • Studies have shown that a daily glucocorticoid dose equivalent to prednisolone ≥ 5 mg, for longer than 1 month, represents an adrenal suppressive dose in a proportion of adults 1.
  • The data from case series of short Synacthen tests performed in populations receiving therapeutic corticosteroid treatment of between 5 mg and 20 mg prednisolone daily, report a variable number of patients (approximately one third to a half) not achieving the target cortisol concentration when 5 mg or more of prednisolone was administered 1.
  • Given the risks of an inadequate glucocorticoid response, individualised glucocorticoid supplementation in addition to ongoing treatment during the peri-operative period (and by extension whenever patients are subjected to any physiological stress), is supported in this group of patients 1.

From the Research

Assessment of Hypothalamic-Pituitary-Adrenal Axis Before Long-Term Withdrawal of Steroids

  • The short synacthen test (SST) is a reliable method for assessing the hypothalamic-pituitary-adrenal (HPA) axis in patients on long-term corticosteroid therapy 2.
  • The SST can be used as an initial assessment of the HPA axis, and the insulin tolerance test (ITT) can be used for those who fail the SST 2.
  • A study found that the SST is a suitable substitute for the ITT in assessing the HPA axis, with a 30-minute cortisol value > 600 nmol/l as a cut-off 3.
  • Another study suggested that baseline serum cortisol, salivary cortisone, and salivary cortisol can be used to predict HPA axis recovery, reducing the need for short synacthen tests by 50%, 46%, and 37%, respectively 4.

Importance of Short Synacthen Test Before Withdrawal

  • The SST is essential in assessing the HPA axis before long-term withdrawal of steroids to avoid adrenal insufficiency 2, 3.
  • A study found that immediate and prolonged suppression of the HPA axis is a common finding in patients undergoing systemic steroid treatment, and the low-dose ACTH test can reliably assess this suppression 5.
  • The SST can help identify patients who are at risk of adrenal insufficiency after steroid withdrawal, allowing for appropriate management and monitoring 2, 3.

Potential Risks and Considerations

  • A personal report described an apparent steroid withdrawal reaction following a short synacthen test, highlighting the potential risks of steroid withdrawal syndrome 6.
  • The SST should be performed with caution, and patients should be closely monitored for signs of adrenal insufficiency after steroid withdrawal 2, 3.

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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.