Urine free cortisol (UFC) measurement is commonly utilised in the investigation and management of Cushing’s syndrome (CS). UFC immunoassays (IA) are susceptible to cross-reactivity with cortisol precursors, metabolites and exogenous glucocorticoids. Liquid chromatography mass spectrometry (LCMS) is more ‘cortisol specific’. However, detection of cortisol conjugates may be relevant in disease detection and monitoring. We measured UFC samples on LCMS, LCMS aligned IA (Abbott) and traditional IA (Roche) in patients with and without CS.
UFC samples were collected from four tertiary Australian centres and analysed on three assays: Roche (reference range (RR) <380 nmol/day), Abbott (RR <280 nmol/day) and LCMS (RR <160 nmol/day).
161 UFC samples from 146 patients were analysed. Correlations against LCMS were: r = 0.9 for Abbott, and 0.73 for Roche (p < 0.0001 for both). There were 45 UFC samples from 35 patients with endogenous CS: 33 Cushing’s disease (CD), 5 ACTH independent CS and 7 ectopic ACTH secretion. Amongst cases of CS, 15 were de novo, with 16, 4 and 10 patients having persistent, relapsed and cured disease respectively.
Concordance rate amongst the three methods was 93% for de novo CS, 69% for persistent CS, 75% for relapsed CS and 60% for cured CS. Of the four relapsed samples, 2 were positive on LCMS and Abbott but 3 positive on Roche. Normalised UFC ratios are shown in table 1. In patients receiving adrenal enzyme inhibitors, Roche UFC ratios were 66% higher than LCMS ratios (p = 0.16). In adrenal CS samples, Roche UFC ratios were 115% higher than LCMS ratios (P= 0.03).
The less specific Roche assay may be more sensitive in the detection of mild relapsed CS and produce higher results in adrenal CS and in patients on enzyme inhibitors due to cortisol conjugate cross-reactivity.