Urinary cortisol metabolites in corticotroph and adrenal tumours

J. Brossaud; D. Ducint; B. Gatta; M. Molimard; A. Tabarin; J. Corcuff

We investigated whether urinary cortisol metabolites could help to diagnose patients with cortisol oversecretion either with benign adrenal or corticotroph tumours.

Liquid chromatography tandem mass spectrometric assay (LC-MSMS) of cortisol (F)m, cortisone, tetra-hydrocortisol (THF), allo-THF, tetra-hydrocortisone (THE), α-cortol, β-cortol, α-cortolone, α-cortolone and internal standard 6-α-methylprednisolone were assayed after deconjugaison and dichloromethane extraction. LC-MSMS was performed with an Acquity UPLC separative module and aTQD detector (Waters, Millport, USA).

In-patients of the endocrine department (n=253, 196F, 49 (20–74)years (median (2.5th–97.5th percentile) were control subjects (n=175 (N)), patients with active Cushing disease’s (n=35, (CD)) or with adrenocortical tumours (n=43, (AS)). The latter were either secreting or non-secreting tumours (the former were subsequently operated and the latter followed-up). Initial diagnosis was made using routine tools including cortisol assays (Fr) performed by RIA (Diasorin, France).

Analytes excretions of the groups are presented in the table (ng/day). Log-transformed cortisol concentrations determined were significantly linearly correlated with a significant bias (Passing-Bablock regression).

Areas under the ROC curves (AUC) were >0.950 for cortisol, THF, α-cortol for the diagnosis of (CD) with an equal 39% sensitivity at 100% specificity for cortisol and α-cortol. Combined analysis of cortisol and α-cortol improved the sensitivity.

AUC were >0.700 for cortisol and β-cortolone for the diagnosis of whole population of (AS). Based on urinary cortisol, 0800 h ACTH and cortisol in plasma, AS tumours could be non-secreting or secreting (at least two positive criteria). AUC were >0.800 for cortisol, β-cortol and β-cortolone for the diagnosis of secreting (AS).

(F) and β-cortolone and to a minor extent both cortols are useful parameter to investigate benign (AS) and (CD). Whether their combined use can facilitate the diagnosis of these diseases has to be investigated in prospective studies.

Table 1
	cortisol	cortisone	THF	alloTHF	THE	α-cortol	β-cortol	α-cortolone	β-cortolone
[N]	101	124	3064	350	3947	162	289	714	423
	(43–533)	(28–429)	(1305–11839)	(11–680)	(781–9924)	(65–519)	(130–946)	(210–2191)	(108–1180)
[CD]	357	297	8637	400	8561	609	872	2643	835
	(181–2012)	(138–618)	(4613–36884)	(49–2052)	(1837–22976)	(229–3266)	(274–6783)	(1228–5375)	(201–3245)
[AS]	66	89	2467	275	3264	162	227	815	187
	(17–216)	(18–277)	(521–8220)	(27–871)	(714–8973)	(36–453)	(43–683)	(143–1997)	(36–497)

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

P55