Biochemical monitoring of classical 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) mostly relies on measurement of serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) concentrations. However, high biological variability, particularly of 17OHP, limits interpretation of results and makes therapeutic adjustments based on single measurements challenging. Recently, 21-deoxycortisol (21DF), has been proposed as a more reliable marker of disease control owing to its adrenal-specific origin and lower biological variability.
Our objective was to compare the intra-individual variability of serum 17OHP, A4 and 21DF, all quantified by liquid chromatography and tandem mass spectrometry (LC-MS/MS) in a cohort of patients with classical salt-wasting CAH.
32 adults (9 males and 23 females) with salt wasting CAH were identified from a single institution. All LC-MS/MS quantified 17OHP, A4 and 21DF measurements performed at PathWest QEII Laboratory between 01/01/2018 and 04/05/2022 were collated for each patient. 20 patients had 2 or more 21DF measurements. Of these, 40 % had 5 or more measurements. The biological component of each patient’s intra-individual coefficient of variation (CVI) was calculated for each analyte. The intra-individual variability was compared between the analytes.
There was strong statistical evidence of lower biological variability (CVI) for A4 than 17OHP (mean difference = -24.1, p=0.003). Other pairwise differences were not significant (A4 versus 21DF p=0.156; 21DF versus 17OHP p=0.104).
The intra-individual variability of LC-MS/MS-quantified 21DF was similar to A4 in adult patients with salt-wasting CAH. Larger prospective studies are required to determine the clinical utility of 21DF measurement for therapeutic monitoring of CAH.