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

Abstract

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.

Adrenocortical suppression in children with nephrotic syndrome treated with corticosteroids

“…Injection Acton Prolongatum® Ferring pharmaceuticals (Saint Prex, Switzerland) (available as a 5-mL vial with a concentration of 60 units per mL, 40 IU = 1 mg) was used [12]. A baseline cortisol of ≤5 mcg/dL was considered as low; any subject with one hour post ACTH cortisol <18.0 microg/dl was diagnosed as having adrenal insu ciency [11,12]. Aliquots for baseline and stimulated cortisol were transported from study site and stored at -20 0 C until tested for estimation of cortisol levels.…”

“…The availability of synacthen is limited in India making this test nonfeasible for testing adrenal function. The modi ed form of ACTH available as ACTH prolongatum has been validated for testing adrenal insu ciency in earlier studies [11]. This form of ACTH is widely used in management of West syndrome in children.…”

“…Acton prolongatum, an ACTH analogue is the most easily available form in India and is used in stimulation tests for detection of adrenocortical insu ciency. It has been shown that both high dose or low dose cosyntropin or ACTH stimulation tests yield almost similar results for detecting secondary adrenocortical suppression[11,12, 18].Early morning fasting serum cortisol levels were used to determine the proportion of patients with baseline serum cortisol suppression and 26 (50%) had levels below the cutoff of 5 mcg/dL (indicating adrenocortical suppression). Children with FRNS disease had the lowest mean level of 5.28mcg/dL while patients with IFRNS course had the highest mean levels of 8.37 mcg/dL.…”