Abstract
The short synacthen test (SST) is widely used in diagnosing adrenal insufficiency as a safer and cheaper alternative to the insulin tolerance test (ITT). Following administration of synacthen, serum Cortisol concentration is measured at 30 and 60 min. Despite its widespread use, consensus lacks among physicians regarding the additional value of the 60 min sample. Furthermore, only the 30 min value has been validated against ITT.
In this large (n = 384) retrospective study, Chitale et al. report on the utility of measuring serum Cortisol at 60 min in addition to the sample at 30 min. The aim was to determine the frequency of misdiagnosis if a 60 min sample was not taken. Several groups were excluded: patients taking corticosteroids not omitted before SST, patients taking oestrogens; patients with congenital adrenal hyperplasia or chronic liver disease and pregnant women. Serum Cortisol was measured 0, 30 and 60 min after intravenous or intramuscular synacthen (250 μg) using Advia-Centaur or Roche-Elecsys immunoassays. Patients ‘passed’ if the Cortisol concentration was ≥550 nmol/L at 30 and 60 min or ‘failed’ if Cortisol was <550 nmol/L at both time points. A partial pass was defined as 30 min Cortisol ≥550 nmol/L and 60 min <550 nmol/L and delayed response as 30 min Cortisol <550 nmol/L and 60 min ≥550 nmol/L. All 75 individuals insufficient at 60 min were also insufficient at 30 min; none had a partial pass and 33 patients had a delayed response. In the latter group, the mean Cortisol was 232 nmol/L (±104), 486 nmol/L (± 29) and 588 nmol/L (± 27) at the three time points.
The 60 min Cortisol was superior as a gold standard versus the 30 min test (higher specificity, positive predictive value, ROC area). In this study 11% of patients undergoing SST would be inappropriately diagnosed with adrenal insufficiency had the 60 min sample not been used. In view of biological and analytical variation, it is recommended that each laboratory should use their own results validated at the three time points.
In conclusion, routinely taking a 60 min sample would improve the specificity of SST and avoid misdiagnosis of adrenal insufficiency.