A 13-Steroid Serum Panel Based on LC-MS/MS: Use in Detection of Adrenocortical Carcinoma

Taylor, David R.; Ghataore, Lea; Couchman, Lewis; Vincent, Royce P.; Whitelaw, Ben; Lewis, Dylan; Díaz‐Cano, Salvador; Galatà, G; Schulte, Klaus–Martin; Aylwin, Simon; Taylor, Norman

doi:10.1373/clinchem.2017.277624

Cited by 94 publications

(68 citation statements)

References 36 publications

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“…This so-called heterogeneity of steroidogenesis observed is a reflection of immature and dedifferentiated cell features, which are the hallmark of ACC [11,13,[15][16][17]. To our knowledge, no serum or urinary steroid metabolites associated with prognostic factors in ACC have been demonstrated to date, but several papers have reported these were useful for the diagnosis of ACC [11][12][13][14][15][16][17][18][19]. Consistent with our recommendation, [17,18] were recommended.…”

Section: Discussionsupporting

confidence: 52%

“…Recently, steroid profiling has emerged as a powerful novel diagnostic tool for ACC [11][12][13][14]. Previous reports demonstrated that examination of serum steroid metabolites using liquid chromatography tandem mass spectrometry (LC-MS/MS) [12,13] or urine steroid metabolites using gas chromatography mass spectrometry (GC-MS) [15][16][17][18][19] are useful for distinguishing ACC from adrenocortical adenoma. Furthermore, the ENSAT recommends a biochemical workup for suspected ACC that includes serum cortisol, aldosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, and 17-beta-estradiol (http://www.ensat.org/page-1317312).…”

Section: Introductionmentioning

confidence: 99%

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Steroid Metabolites for Diagnosing and Predicting Clinicopathological Features in Cortisol-Producing Adrenocortical Carcinoma.

Suzuki

Minamidate

Shiga

et al. 2020

Preprint

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About 60% of adrenocortical carcinomas (ACC) are functional, and Cushing's syndrome is the most frequent diagnosis which has been revealed to have particularly poor prognosis. Since 30% of ACC present steroid hormone-producing disorganization, measurement of steroid metabolites in suspected ACC is recommended. Previous reports demonstrated that steroid hormone precursors or its urine metabolites, using liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC-MS) respectively, are useful for distinguishing ACC from adrenocortical adenoma. However, whether steroid metabolites can predict pathological characteristics or prognosis has not been elucidated. Here, we examined 12 serum steroid metabolites using immunoassay, which is a more rapid and less costly method compared to LC-MS/MS, in cortisol-producing ACC and cortisol-producing adenomas (CPA). Further, the correlation of each steroid metabolite to the stage classification and pathological status in ACC was analyzed. Reflected disorganized steroidogenesis, immunoassay revealed all basal levels of steroid precursors were significantly increased in cortisol-producing ACC compared to CPA; especially 17- hydroxypregnenolone (androgen precursor) and 11-deoxycorticosterone (mineralocorticoid precursor) showed large area under ROC curve with high sensitivity and specificity, when setting the cut-off at 1.78 ng/ml and 0.4 mg/ml, respectively. In cortisol-producing ACC, 11-deoxycortisol (glucocorticoid precursor) showed significant positive correlations to predictive prognostic factors of ENSAT classification, while testosterone showed significant positive correlations to Ki67-index in both men and women. In conclusion, measurement of serum steroid metabolites using immunoassay has great potential not only for diagnosis but also for prediction of the clinicopathological features associated with disease prognosis of ACC, as a simple non-invasive method.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Steroid Metabolites for Diagnosing and Predicting Clinicopathological Features in Cortisol-Producing Adrenocortical Carcinoma.

Suzuki

Minamidate

Shiga

et al. 2020

Preprint

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“…Third, we included in our series also ENSAT stage IV tumors, which are frequently associated with clinically more severe steroid phenotypes due to their large tumor mass. This fact, however, also applies to the two series referred to above (14,18) and that by Kerkhofs et al (15). Fourth, we deliberately excluded aldosterone-producing adenomas from our series.…”

Section: Discussionmentioning

confidence: 66%

“…The recent study by Taylor et al (18) described the development of an LC-MS/MS method for quantitation of 13 steroid hormones in serum and applied this method to different adrenal tumors. With the exception of 17-OH-pregnenolone, all analytes accessible in the method by Taylor et al were also quantified in the present paper.…”

Section: Discussionmentioning

confidence: 99%

“…In a very small study with only ten ACC patients, Taylor et al suggested that serum steroid panel analysis may help in the differential diagnosis of ACC and non-ACC adrenal tumors (e.g. ACA) (18) and similar panel analyses have been successfully conducted in cortisolproducing adenomas (19). LC-MS/MS analysis of serum or plasma samples would not only facilitate sampling but also speed up laboratory diagnostics and thereby facilitate the difficult differential diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma

Schweitzer

Kunz

Kurlbaum

et al. 2019

European Journal of Endocrinology

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Objective: Current workup for the pre-operative distinction between frequent adrenocortical adenomas (ACAs) and rare but aggressive adrenocortical carcinomas (ACCs) combines imaging and biochemical testing. We here investigated the potential of plasma steroid hormone profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) for the diagnosis of malignancy in adrenocortical tumors. Design: Retrospective cohort study of prospectively collected EDTA-plasma samples in a single tertiary reference center. Methods: Steroid hormone profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) in random plasma samples and logistic regression modeling. Results: Fifteen steroid hormones were quantified in 66 ACAs (29 males; M) and 42 ACC (15 M) plasma samples. Significantly higher abundances in ACC vs ACA were observed for 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA, DHEAS and estradiol (all P < 0.05). Maximal areas under the curve (AUC) for discrimination between ACA and ACC for single analytes were only 0.76 (estradiol) and 0.77 (progesterone), respectively. Logistic regression modeling enabled the discovery of diagnostic signatures composed of six specific steroids for male and female patients with AUC of 0.95 and 0.94, respectively. Positive predictive values in males and females were 92 and 96%, negative predictive values 90 and 86%, respectively. Conclusion: This study in a large adrenal tumor patient cohort demonstrates the value of plasma steroid hormone profiling for diagnosis of ACC. Application of LC-MS/MS analysis and of our model may facilitate diagnosis of malignancy in non-expert centers. We propose to continuously evaluate and improve diagnostic accuracy of LC-MS/MS profiling by applying machine-learning algorithms to prospectively obtained steroid hormone profiles.

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Development and validation of a liquid chromatography–tandem mass spectrometry method for the simultaneous analysis of androgens, estrogens, glucocorticoids and progestagens in human serum

Iannone

Dima

Sciarra

et al. 2022

Biomedical Chromatography

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We present a liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 16 endogenous steroids (androgens, estrogens, glucocorticoids and progestogens) in human serum. Samples (250 μl of matrix) were extracted with t-butylmethyl ether prior to LC-MS/MS analysis. The chromatographic separation was achieved on a reversed-phase column using a methanol-water gradient. The HPLC was coupled to a triple quadrupole mass spectrometer equipped with an electrospray ionization source with acquisition in multiple reaction monitoring mode.

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A 13-Steroid Serum Panel Based on LC-MS/MS: Use in Detection of Adrenocortical Carcinoma

Abstract: Serum steroid paneling by LC-MS/MS is useful for diagnosing ACC by combining the measurement of steroid hormones and their precursors in a single analysis.

Cited by 94 publications

References 36 publications

Steroid Metabolites for Diagnosing and Predicting Clinicopathological Features in Cortisol-Producing Adrenocortical Carcinoma.

Steroid Metabolites for Diagnosing and Predicting Clinicopathological Features in Cortisol-Producing Adrenocortical Carcinoma.

Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma

Development and validation of a liquid chromatography–tandem mass spectrometry method for the simultaneous analysis of androgens, estrogens, glucocorticoids and progestagens in human serum

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