ACTH measured by Immulite1000® and Elecsys® assay platforms in suspected cases of hypocortisolism: A word of caution.

Objective: Several reports suggested that ACTH level measured by Immulite 1000® may be falsely elevated leading to misdiagnosis of etiology of Cushing syndrome. However, when it comes to fallacies of ACTH measurement in suspected cases of hypocortisolism, evidence is limited. We explored the performance of ACTH assays using Immulite 1000® and Elecsys® Cobas immunoassay platforms in subjects with hypocortisolism.

Methods: In this observational, cross-sectional study, 104 patients with HbE/Beta thalassemia were subjected to 9 am serum cortisol, direct renin concentration and plasma aldosterone. Plasma ACTH was measured in Immulite 1000® and Elecsys® Cobas platforms. Both 1 μg and 250 μg Synacthen® stimulation tests were performed to diagnose adrenal insufficiency.

Results: Amongst 104 patients with HbE/Beta thalassemia, 34 had primary adrenal insufficiency, 9 had secondary adrenal insufficiency and 33 had subclinical adrenal insufficiency. Mean plasma ACTH (n=104) measured by Immulite 1000® and Elecsys® was 83.42 ± 63.46 pg/ml versus 52.10 ± 38.14 pg/ml respectively (p <0.001). The values had good correlation (r= 0.341, p <0.001); however, the agreement between measured values was not strong (Cohen's κ = 0.208, p= 0.001). With regards to the diagnosis of primary adrenal insufficiency, specificity of Immulite 1000® was low as compared to Elecsys® (27.86% vs. 80.32%). Furthermore, 2 patients with secondary adrenal insufficiency had inappropriately elevated ACTH measured at Immulite 1000® assay platform.

Conclusion: Use of Immulite 1000® platform may result in falsely elevated ACTH values. Physicians should exercise caution while interpreting the results and repeat test using a different assay platform may be considered.