Diagnostic Value of Urinary Steroid Profiling in the Evaluation of Adrenal Tumors

Kerkhofs, Thomas M.A.; Kerstens, Michael; Kema, Ido P.; Willems, Tineke P.; Haak, Harm R.

doi:10.1007/s12672-015-0224-3

Cited by 94 publications

(79 citation statements)

References 22 publications

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“…Analysis of steroid hormones by gas chromatography mass spectrometry (GC-MS) in urine samples is a useful tool for the diagnosis of steroid synthesis disorders such as congenital adrenal hyperplasia (25,26,27,28) and P450 oxidoreductase deficiency (27,29). It has also been successfully applied for the discrimination between benign and malignant adrenal masses (14,30,31,32).…”

Section: Discussionmentioning

confidence: 99%

“…Some decades ago, it has already been considered to exploit variabilities of steroidogenic hormone production as markers of malignancy in adrenal masses (12,13). More recently, it has been shown that steroid profiling by gas chromatography mass spectrometry (GC-MS) of urine samples collected over 24 h has diagnostic value in discriminating benign and malignant adrenocortical tumors (14,15).…”

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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma

Schweitzer

Kunz

Kurlbaum

et al. 2019

European Journal of Endocrinology

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“…However, the panel acknowledges that the published evidence for this suggestion is very low (184,193). A very promising new tool to discriminate benign from malignant adrenocortical tumors appears the analysis of a comprehensive urinary steroid profile measured by GC-MS or LC-MS (194,195). (Fig.…”

Section: Reasoningmentioning

confidence: 99%

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Arlt

Bancos

et al. 2016

European Journal of Endocrinology

1,335

1,571

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By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected recommendations: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1 mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50 nmol/L (1.8 µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1 mg dexamethasone >138 nmol/L (>5 µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients www.eje-online.org European Journal of Endocrinology175:2 G2 Clinical Practice Guideline M Fassnacht and others ESE and ENSAT guideline on adrenal incidentalomawith an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal inciden...

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“…More recently, in a series of 102 patients with ACAs and 45 with ACCs, urinary steroid profiling differentiated ACCs from ACAs with a sensitivity and specificity of 90% (Arlt et al 2011). Kerkhofs et al (2015) showed that tetrahydro-11-deoxycortisol (THS) at a cut-off value of 2.35 mmol/24 h differentiated ACC (nZ27) from other adrenal disorders (nZ125) with a sensitivity of 100% and specificity of 99%.…”

Section: Geneticsmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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Diagnostic Value of Urinary Steroid Profiling in the Evaluation of Adrenal Tumors

Cited by 94 publications

References 22 publications

Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma

Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

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