Testing the hypothalamo-pituitary-adrenal axis

Abstract

Aims There remains considerable debate about the best way to assess adrenal function. In our unit, adrenal function in children with suspected pituitary disease is initially tested using dynamic testing of the HPA axis (insulin tolerance test (ITT) or glucagon stimulation test (GST)), with failures (peak cortisol Methods This study took place in a single paediatric endocrinology unit. Endocrine records from November 1999– March 2010 identified patients having anterior pituitary function testing with ITT or GST, and also subsequent SST. Demographic, clinical and endocrine data were subsequently extracted from clinical and laboratory records. Results Over the 11 year collection period 509 ITTs and 164 GSTs were performed. Subsequent SSTs for failed tests were performed in 11 (2.2%) ITTs and 18 (11.0%) GSTs. Overall 42 children with paired tests were identified; 19 underwent ITT (median age 15.2 years, 12 males) and 23 GST (median age 8.8 years, 12 males), followed by SST within one year. The correlation coefficient between baseline (9 am) cortisols on the 2 consecutive tests was 0.36 (p=0.02); using a cutoff of ≥200 nmol/L there was concordance in 29/42 (69%). For ITTs there was a correlation coefficient of 0.34 (p=0.15) between the peak ITT cortisol compared to the 30 minute SST value. Using cutoffs of a peak ITT/GST cortisol level of ≥500 nmol/l and ≥550 nmol/l for the 30 minute SST cortisol level there was concordance in 14/19 (73.7%) ITTs. For GST the correlation coefficient was 0.56 (p=0.0057), and concordance in 11/23 (47.8%). Conclusion There is considerable variation in baseline cortisol levels, making its use and also that of incremental cortisol levels unhelpful in the diagnosis of adrenal insufficiency. Whilst there is a better correlation between the SST cortisol levels at 30 minutes and peak cortisol levels during the GST compared to the ITT concordance between tests is better in the latter. It would appear that the ITT is a good diagnostic test for the HPA axis; the GST less so. For patients having a subnormal cortisol response during the GST we would recommend SST testing.