What is the use and dosage of Tetracosactide (Synacthen) in assessing adrenal gland function?

Tetracosactide (Synacthen) for Adrenal Function Assessment

Primary Use and Standard Dosage

Tetracosactide (Synacthen) is administered at 0.25 mg (250 μg) intramuscularly or intravenously to diagnose adrenal insufficiency, with serum cortisol measured at baseline and 30 minutes post-administration; a peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency. 1

Diagnostic Protocol

Standard Short Synacthen Test

• Administer 0.25 mg tetracosactide via IM or IV route 1, 2, 3
• Obtain baseline serum cortisol and plasma ACTH before administration 1, 2
• Measure serum cortisol at 30 minutes (and optionally at 60 minutes) post-injection 2, 3
• Preferably perform in the morning, though not strictly mandatory 2

Interpretation Criteria

• Peak cortisol >500 nmol/L (>18 μg/dL) = Normal adrenal function 1, 2
• Peak cortisol <500 nmol/L (<18 μg/dL) = Diagnostic of primary adrenal insufficiency 1

Baseline Cortisol Interpretation (Without Stimulation)

• Basal cortisol <250 nmol/L with elevated ACTH in acute illness = Diagnostic of primary adrenal insufficiency 1, 2
• Basal cortisol <400 nmol/L with elevated ACTH in acute illness = Strong suspicion of primary adrenal insufficiency 1

Clinical Indications

When to Use the Test

• Equivocal cases where paired baseline cortisol and ACTH measurements are inconclusive 1
• Hypo-osmolar hyponatremia to distinguish adrenal insufficiency from SIADH, as both present identically 2
• Suspected partial adrenal insufficiency when clinical suspicion exists but baseline values are uncertain 1
• Patients at risk for developing primary adrenal insufficiency, such as those with 21-hydroxylase autoantibodies 2

Critical Safety Considerations

When NOT to Delay for Testing

Treatment of suspected acute adrenal crisis must NEVER be delayed for diagnostic procedures. 1, 2, 3

• If adrenal crisis is suspected, immediately administer IV hydrocortisone 100 mg followed by 100 mg every 6-8 hours 1
• Administer 0.9% saline at 1 L/hour until hemodynamic improvement 1, 2
• Obtain blood samples for cortisol and ACTH before treatment if possible, but do not delay therapy 2

Important Confounding Factors

Medications That Interfere with Results

• Oral prednisolone or dexamethasone can confound interpretation of serum cortisol levels 1, 2
• Inhaled steroids (particularly fluticasone) may affect test results 1, 2
• Discontinue exogenous steroids before performing the test when clinically feasible 3

Low-Dose Alternative (Primarily Pediatric)

While the standard 0.25 mg dose is most widely used (92% of centers), some centers use low-dose protocols (1 μg), particularly in pediatrics 4. However:

• Significant variability exists in low-dose preparation methods, with intramethod coefficients of variation ranging from 2.1% to 109% 4
• The 5% dextrose dilution method shows the least variability (CV 2.1%) if low-dose testing is chosen 4
• The standard high-dose test remains preferred due to reliability and consistency 3, 4

Diagnostic Algorithm Context

The Synacthen test fits into the broader diagnostic workup as follows:

1. First-line testing: Paired morning serum cortisol and plasma ACTH 1, 2
2. If equivocal: Proceed to Synacthen stimulation test 1
3. If positive for primary adrenal insufficiency: Measure 21-hydroxylase autoantibodies to identify autoimmune etiology 1, 2
4. If autoantibodies negative: Obtain CT imaging of adrenals to evaluate for structural causes 1, 2