Long-acting Porcine Sequence ACTH (Acton Prolongatum) Stimulation Test is a Reliable Alternative Test as Compared to the Gold Standard Insulin Tolerance Test for the Diagnosis of Adrenal Insufficiency

CONTEXT: As synacthen use is not licensed in India and there are concerns about the safety of the insulin tolerance test (ITT), an alternative dynamic test to diagnose adrenal insufficiency (AI) is required. OBJECTIVE: The study aimed to evaluate the diagnostic performance of the Acton Prolongatum stimulation test (APST) with a standard ITT for the diagnosis of AI. DESIGN: Prospective study comparing two diagnostic tests. PARTICIPANTS: Six healthy volunteers and 53 suspected or known AI patients. MEASUREMENTS: Serum cortisol response to ITT and APST. RESULTS: The median (95% confidence interval [CI]) peak cortisol levels among healthy volunteers in ITT and APST were 17 (14.58–19.08) and 30.5 (22.57–34.5) μg/dL. Of the 53 patients (age: 39.6 ± 9.38 years; females: 38 [71.1%]), 34 had AI (peak ITT serum cortisol < 14.5 μg/dL) whereas 19 had a normal hypothalamic-pituitary-adrenocortical (HPA) axis. In the receiver operator characteristic curve analysis, 60-min APST cortisol had an area under the curve of 0.984 (95% CI: 0.904–1.00, P < 0.0001). The best accuracy was obtained at a cut-off of 16.42 μg/dL (sensitivity: 97.7% [95% CI: 87.7–99.9%]; specificity: 100% [69.2-100%]). Forty-three of the 53 patients with suspected AI had hypoglycemic symptoms during ITT and two of them required intravenous dextrose, whereas, none had adverse events during APST. The ITT was incomplete in two patients whereas all completed APST. CONCLUSIONS: APST is a simple, safe, and reliable alternative to ITT for the diagnosis of AI; 60-min serum cortisol of 16.42 μg/dL in APST best distinguishes the AI patients from those with adequate cortisol response.