Diagnostic Utility of Low-Dose Cosyntropin Stimulation Test for Central Adrenal Insufficiency

Consensus regarding the diagnostic cutoff values for cortisol responses to low-dose cosyntropin testing (LDT) and its specific advantages over standard high-dose test (HDT) in assessing the pituitary-adrenal axis in children is lacking.

In a retrospective study, patients who underwent sequential LDT and HDT were classified into two groups depending on the reason for testing: prolonged systemic glucocorticoid exposure (group 1) or suspected hypothalamic-pituitary dysfunction (group 2). Sensitivity and specificity analysis of varying cortisol levels during LDT in diagnosing adrenocorticotropic hormone (ACTH) deficiency (ACTHD) were calculated via the receiver operating characteristic curve analysis against the reference diagnostic test HDT. ACTHD was defined as peak cortisol level <18 μg/dL (500 nmol/L) in HDT.

This analysis included 112 patients, of whom 20 were diagnosed with ACTHD. There was a strong correlation between peak cortisol levels during LDT and HDT (r = 0.93, p < 0.001). A cortisol peak of 13.5 μg/dL (372 nmol/L) during the LDT had the best diagnostic accuracy (Sensitivity 90%, Specificity 90%: area under the curve 0.973 [95% CI: 0.945-1, p < 0.001]) in the entire cohort. A higher cortisol level was needed for group 1 to achieve comparable performance to group 2 (14.5 vs. 11.5 μg/dL [317 nmol/L], respectively).

The strong correlation between cortisol responses in the LDT and HDT suggests that, when appropriately lower cutoff values are applied, the LDT provides results comparable to the HDT.