Endocrine Abstracts

Context: Recent guidelines recommend a diagnosis of adrenal insufficiency when stimulated peak cortisol level falls below 500 nmol/l. This may not be valid when using a highly specific cortisol immunoassay or cortisol measured by liquid chromatography-mass spectroscopy.

Objective: Determine the diagnostic threshold for adrenal insufficiency using a highly specific cortisol assay.

Design: For 4 months, all subjects having a dynamic test of adrenal reserve had results measured using the historical cortisol assay (Roche Cortisol) and the newer assay (Roche Cortisol II).

Setting: Tertiary level endocrine testing unit.

Interventions: Cosyntropin stimulation tests (1 and 250 μg), insulin hypoglycaemic tests and glucagon stimulation tests.

Main outcome measures: Subjects were categorized according to the results from the traditional assay (normal considered >500 nmol/l) along with clinical case adjudication where necessary. Results from the Cortisol II assay were reported in both normals and those deemed to have adrenal insufficiency. Passing-Bablock and Bland Altman plots described the difference between the two assays; ROC curve analysis was performed to generate new diagnostic thresholds.

Results: The Roche Cortisol II compared very closely with measures by LCMS-MS and generated cortisol levels ≈30% lower than the older immunoassay. Many normal subjects had peak cortisols as low as 300 nmol/l with the new assay. The optimized new diagnostic threshold for adrenal insufficiency was 350 nmol/l with a sensitivity of 91% and specificity 97%.

Conclusions: Transition to a more specific cortisol assay requires re-calibration of diagnostic thresholds for dynamic tests of adrenal insufficiency. With the Roche Cortisol II assay, a cut-off of 350 nmol/l would appear to best replace the traditional 500 nmol/l although a number of normal subjects may also be very close to this level. Adrenal insufficiency will be significantly over-diagnosed if the effect of assay change is not considered.