Duration of Action of Cosyntropin (Corticotropin)
Cosyntropin stimulates maximal adrenal cortical secretion within 30-60 minutes after administration, with cortisol levels measured at these specific time points to assess adrenal function. 1
Pharmacodynamic Timeline
The FDA-approved labeling specifies the precise timing for cosyntropin testing 1:
- Baseline cortisol: Obtained immediately before administration
- Peak cortisol response: Measured at exactly 30 and 60 minutes post-injection
- Maximal adrenal stimulation: Achieved with a single 0.25 mg dose, equivalent to 25 units of natural ACTH 1
Duration in Normal vs. Impaired Adrenal Function
In Patients with Normal Adrenal Function
The cortisol response peaks between 30-60 minutes, with 54% of patients reaching maximum levels at 60 minutes. 2 Research demonstrates that:
- Normal individuals show stimulated cortisol levels ≥18 mcg/dL at 30 or 60 minutes 1, 2
- The lowest cortisol values in confirmed normal HPA axis patients were 15.7 mcg/dL at 30 minutes and 17.9 mcg/dL at 60 minutes 3
- Weight status affects peak timing: overweight/obese individuals tend to peak at 30 minutes, while normal/underweight individuals peak at 60 minutes 2
In Patients with Adrenal Insufficiency
Patients with adrenal insufficiency fail to achieve adequate cortisol response at both 30 and 60 minutes, with stimulated levels remaining below 18 mcg/dL. 1 The 2017 SCCM/ESICM guidelines recommend using the 250-μg ACTH stimulation test to diagnose critical illness-related corticosteroid insufficiency (CIRCI), with a delta cortisol <9 μg/dL indicating inadequate response 4.
Critical Timing Considerations
Both 30- and 60-minute measurements are necessary to avoid overdiagnosing adrenal insufficiency, as 11% of patients who fail at 30 minutes pass at 60 minutes. 2 The FDA label explicitly states that cortisol should be measured "exactly 30 minutes and 60 minutes after administration" 1.
Primary vs. Secondary Adrenal Insufficiency
- Primary adrenal insufficiency: 30-minute cortisol determination establishes diagnosis in >95% of cases 5
- Secondary adrenal insufficiency: 60-minute measurement is more specific, establishing diagnosis in >97% of cases 5
Adrenal Suppression from Single-Dose Etomidate
One study examining etomidate-induced adrenal suppression found that although a single 0.3 mg/kg induction dose caused decreased adrenal response at 4 hours, levels returned to normal by 12 hours, with all measured cortisol levels remaining within normal laboratory ranges throughout 4.
Common Pitfalls to Avoid
Do not rely solely on 30-minute cortisol values, as this may lead to false-positive diagnoses of adrenal insufficiency. 2 Additionally:
- Glucocorticoids and spironolactone must be stopped on the day of testing; long-acting glucocorticoids require longer discontinuation 1
- Estrogen-containing drugs should be stopped 4-6 weeks before testing, as they elevate cortisol-binding globulin and falsely increase total cortisol levels 1
- The specific cortisol assay used affects cutoff values—newer assays like the Roche Elecsys Cortisol II may require lower cutoffs than the traditional 18 mcg/dL 3