Endocrine Abstracts

Background: The Synachten test is used to diagnose for adrenal insufficiency (AI) and non-classical congenital adrenal hyperplasia (CAH). The cut-off levels for s-cortisol and s-17-hydroxyprogesterone are derived from immunoassays that were not well standardized and are no longer in use. Introduction of liquid chromatography tandem mass spectrometry (LCMSMS) could resolve the lack of standardization of steroid hormone assays and enable increased diagnostic accuracy.

Aim: Define cut-off values for s-cortisol and s-17OH-progesterone by LCMSMS after intravenous administration of 250 μg tetracosactide acetate (Synachten).

Methods: The Synachten test was performed in healthy individuals (n=60) and patients referred for evaluation of adrenocortical function (n=42). Steroids were assayed by LCMSMS. Cut-off level for s-cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n=55), and for 17-OH-progesterone as the 97.5% percentile in the healthy women.

Results: Cortisol cut-off levels were 415 and 493 nmol/l at 30 and 60 min, respectively. All controls had higher cortisol at 60 compared to 30 min. Applying the current cut-off of 550 nmol/l, 27 healthy controls would have had a false negative test at 30 min, and six at 60 min. For s-17-OH-progesterone the cut-off levels were 10.5 and 11.1 nmol/l at 30 and 60 min, respectively. Forty-two patients performed the test for suspected AI or non-classic CAH. Applying the new cut-offs, seven who had AI according to old criteria, now scored normal.

Conclusions: Cut-off levels for s-cortisol after Synacthen test are lower than the commonly recommended discriminating levels when cortisol is analyzed by LCMSMS. When applied, a significant proportion of patients can be re-categorized from adrenal insufficiency to healthy. We recommend using the 60 min value as standard, as cortisol increased from 30 to 60 min in all controls.