Lack of sensitivity of the 1-μg low-dose ACTH stimulation test in a paediatric population with suboptimal cortisol responses to insulin-induced hypoglycaemia


Correspondence: Dr Michael J. O'Grady, Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Subiaco, WA 6008, Australia. Tel.: +61 8 9340 8742; Fax: +61 8 9340 8605; E-mail:



The insulin-tolerance test (ITT) is the gold standard for evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. The low-dose ACTH stimulation test is increasingly used for evaluation of secondary adrenal insufficiency as several studies performed in adults have demonstrated high sensitivity and specificity when compared to the ITT. Whether the ACTH stimulation test demonstrates similar sensitivity in a paediatric and adolescent population compared with the gold standard is unclear.


To compare the sensitivity of the low-dose (1-μg) Synacthen test (LDSST) and the gold-standard ITT in a paediatric and adolescent population.

Design and Patients

A retrospective review of 42 consecutive LDSSTs in children and adolescents with suboptimal cortisol responses (peak <500 nm) on ITT.


Thirty-one patients (74%) had an adequate cortisol response to low-dose Synacthen (sensitivity 26%). Patients had a higher cortisol increment with the LDSST than ITT (median Δ cortisol 294 vs 168 nm, P < 0·0001) and correspondingly a higher cortisol peak (median peak cortisol 572 vs 396 nm, P < 0·0001). Patients who had a suboptimal peak cortisol both on ITT and on LDSST had a lower baseline cortisol on ITT (median 178 vs 227 nm, P = 0·04). Peak cortisol on ITT was significantly higher in patients who had a subsequent normal LDSST than those that did not (median 417 vs 300 nm, P = 0·0005).


The 1-μg LDSST lacks sensitivity in detection of secondary adrenal insufficiency in children when compared to the gold-standard ITT.