Utility of LC-MS/MS based adrenal venous steroid profiling: Should cortisol remain the gold standard for selectivity and comparisons to aldosterone?

M Peitzsch; T Dekkers; M Haase; LJ Schultzekool; ARRM Hermus; D Blondin; FCGJ Sweep; G Antoch; G Siegert; J Lenders; J Deinum; HS Willenberg; G Eisenhofer

doi:10.1055/s-0034-1372151

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Utility of LC-MS/MS based adrenal venous steroid profiling: Should cortisol remain the gold standard for selectivity and comparisons to aldosterone?

M Peitzsch ¹, T Dekkers ², M Haase ³, LJ Schultzekool ², ARRM Hermus ², D Blondin ³, FCGJ Sweep ², G Antoch ³, G Siegert ¹, J Lenders ², J Deinum ², HS Willenberg ³, G Eisenhofer ¹

¹Universitätsklinikum Carl Gustav Carus an der TU Dresden, Institut für Klinische Chemie und Laboratoriumsmedizin, Dresden, Germany
²Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
³Universitätsklinik, Düsseldorf, Germany

Abstract

Background: Comparisons of aldosterone with cortisol during adrenal venous sampling (AVS) provide the currently recommended technique for distinguishing unilateral adenomas from bilateral adrenal hyperplasia during the diagnostic work-up of patients with primary aldosteronism. Selectivity of AVS is routinely established from adrenal venous (AV) to peripheral venous (PV) ratios of cortisol, but is more accurately indicated by AV: PV ratios of plasma metanephrine.

Objective: Here we describe a novel liquid-chromatography tandem mass spectrometric (LC-MS/MS) assay for profiling plasma levels of 15 adrenal steroids during AVS, with and without ACTH stimulation.

Methods: Selectivity of AVS was established by AV: PV ratios of plasma metanephrine larger than 12. Concentrations of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, pregnenolone, cortisone, cortisol, 11-deoxycortisol, 17-hydroxy-progesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, 21-deoxycortisol, 18-oxo-cortisol and 18-hydroxy-cortisol were compared in PV and AV plasma samples from 35 patients with and without ACTH stimulation. Aldosterone and cortisol levels measured by LC-MS/MS were compared with levels measured by immunoassay.

Results: Median AV: PV ratios of plasma cortisol (17) were lower than those of corticosterone (52), 11-deoxycorticosterone (68), pregnenolone (72), 11-deoxycortisol (55) and 17-hydroxy-progesterone (57). ACTH stimulation increased AV plasma concentrations of cortisol 6-fold, but had larger effects on other steroids such as corticosterone, which increased by 36-fold. As a result AV plasma concentrations of corticosterone relative to cortisol increased from 6% to 38%. Method comparisons indicated agreement of concentrations of cortisol measured by immunoassay and LC-MS/MS.

Conclusion: Compared to other adrenal steroids, cortisol provides a less sensitive marker for selectivity of AVS.