SFEBES2015 Poster Presentations Steroids (49 abstracts)
Discrimination of adrenocortical carcinoma from other adrenal lesions: use of a new 13 steroid serum panel based on LC–MS/MS
David Taylor 1 , Lea Ghataore 1 , Royce Vincent 1 , Roy Sherwood 1 , Ben Whitelaw 2 , Dorota Dworakowska 2 , Klaus-Martin Schulte 3 , Salvadore Diaz-Cano 4 , Dylan Lewis 5 , Simon Aylwin 2 & Norman Taylor 1
1Department of Clinical Biochemistry (Viapath Analytics), King’s College Hospital, London, UK; 2Department of Endocrinology, King’s College Hospital, London, UK; 3Department of Surgery, King’s College Hospital, London, UK; 4Department of Histopathology, King’s College Hospital, London, UK; 5Department of Radiology, King’s College Hospital, London, UK.
Adrenocortical carcinoma (ACC) is a rare malignancy, but accounts for up to 11% of adrenal masses investigated in referral centres. Diagnosis remains a challenge. Up to two thirds are biochemically inactive, resulting from de facto enzyme deficiencies in the steroid hormone biosynthetic pathways, as shown by urine steroid profiling by gas chromatography-mass spectrometry. Increased metabolites of pathway intermediates in ACC discriminate it from benign adrenal lesions and provide markers for follow up. Serum assays for most intermediates (e.g. 17-hydroxypregnenolone) are unavailable, due to low demand or lack of immunoassay specificity. Serum steroid analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS) is increasingly replacing immunoassay, especially for those most subject to cross-reaction. We have developed an LC–MS/MS method for measurement of testosterone, progesterone, androstenedione, DHEAS, pregnenolone, 11-deoxycorticosterone, corticosterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, cortisol, and cortisone in serum. We investigated its utility in discriminating ACC (six cases) from 24 non-ACC adrenal lesions (11 phaeochromocytoma, three cortisol-producing and three aldosterone-producing adenomas, and seven lesions demonstrating no hormonal excess) and 61 healthy controls. Samples containing internal standards were prepared for LC–MS/MS by sequential protein precipitation and liquid–liquid extraction. Steroids were resolved on a reverse-phase C18 column with the MS operated in positive APCI ionisation mode. In the ACC cases, between four and 10 steroids were increased (mean=6), whilst in the non-ACC group up to two steroids were increased. 11-Deoxycortisol was markedly increased in all ACC cases, whilst increases were also seen for androstenedione (five cases), 17-hydroxyprogesterone (four cases) and pregnenolone, 17-hydroxypregnenolone, 11-deoxycorticosterone, and DHEAS (three cases each). The cortisol:11-deoxycortisol ratio best discriminated between ACC (mean=14.9), non-ACC (335.9), and healthy controls (324.9, P=0.003). In conclusion, serum steroid panelling by LC–MS offers a promising diagnostic test for ACC by combining the measurement of steroid hormones and their precursors in a single analysis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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