Urinary steroid profile in adrenocortical tumors

doi:10.1016/S0753-3322(00)80043-8

Biomedicine & Pharmacotherapy

Volume 54, Supplement 1, June 2000, Pages 194s-197s

https://doi.org/10.1016/S0753-3322(00)80043-8 Get rights and content

Summary

Determination of the urinary steroid profile has been proposed as a sensitive tool for diagnosing adrenocortical tumors.

The urinary steroid profiles were determined for patients with adrenocortical tumors. Urinary steroids were extracted, derivatized to form methyloxime-trimethylsilyl ether and analyzed by gas chromatography/mass spectrometry.

Patients with adrenal adenomas from primary hyperaldosteronism had increased metabolites of 18-hydroxycorticosterone and aldosterone, and those with Cushing's syndrome had elevated excretion of 11-deoxycortisol, cortisol, 18-hydroxycortisol, and cortisone metabolites. In patients with adrenocortical carcinomas, increased levels of metabolites of 11-deoxycortisol or 3β-hydroxy-5-ene steroids were observed. The urinary steroid profiles of adrenal adenomas and adrenocortical carcinomas were quite different, suggesting the diagnostic validity for discriminating malignant from benign diseases.

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Cited by (36)

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping
2024, eBioMedicine
Diagnosing Cushing’s syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS.
We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing’s disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female).
Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11β-OH-An + 11β-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%.
GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes.
The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung.
A Proposal for Nomenclature Revision of Nonfunctioning Adrenal Incidentalomas as Adrenal Lesions of Undetermined Secretion of Adrenal Steroids (ALUSAS)
2022, Endocrine Practice
In this commentary we propose a change of the nomenclature of non-functioning adrenal incidentalomas (NFAI) to adrenal lesions of undetermined secretion of adrenal steroids (ALUSAS) since there are mounting evidence suggesting that a substantial proportion of so-called NFAIs do actually secrete steroids in excess. In fact, it is known that some NFAIs develop ACS over time. In the commentary we justify the change of term by summarizing the evidence that shows that NFAIs present a higher cardiometabolic risk than the general population, and the metabolomics studies in which an increase in cortisol metabolites is observed in patients with NFAI.
Determination of the steroid profile in alternative matrices by liquid chromatography tandem mass spectrometry
2020, Journal of Steroid Biochemistry and Molecular Biology
The simultaneous determination of a broad panel of steroids provides more accurate information about the hormonal status than the detection of a single hormone. For that reason, the determination of the steroid profile, i.e. the endogenous steroid hormones and their main metabolites, has become the most powerful tool for the study of hormonal imbalances. The usefulness of the evaluation of the steroid profile in urine and plasma is widely accepted. However, despite its broad potential applicability, the evaluation of the whole steroid profile in alternative matrices such as amniotic fluid, saliva and breast milk remains almost unexplored. In this research we developed and validated a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the quantification of several steroids and their metabolites in amniotic fluid (28 analytes), saliva (15) and breast milk (12). Sample preparation, chromatographic conditions and mass spectrometric conditions (e.g. ionization species or ion source parameters) were optimized. The method was shown to be linear in the range of endogenous concentrations for all studied metabolites. Intra- and inter-assay accuracies were between 80% and 120% while intra- and inter-precisions were below 20% for all analytes in all matrices. The applicability of the method was evaluated by the comparison between the concentration ranges obtained in healthy volunteers (n = 30 per matrix) and the scarce data previously reported in literature. The concentration ranges for several analytes are reported for the first time. The present methodology represents a useful tool for the comprehensive evaluation of the steroid profile in alternative matrices and can be applicable for different clinical purposes.
Steroid metabolomics: machine learning and multidimensional diagnostics for adrenal cortical tumors, hyperplasias, and related disorders
2019, Current Opinion in Endocrine and Metabolic Research
Citation Excerpt :
The possibility to use steroid profiles for diagnosis and/or prognostic risk stratification in ACC has consequently received several decades of attention from multiple groups [7–11,19,23,49,51–53]. Most steroid profiling studies in ACC have focused on the urinary steroidome usually with GC–MS [7–11,53] or other GC-based methods [49,51], but in one report using LC coupled to a high-resolution mass spectrometer [23]. Increases in metabolites of 11-deoxycortisol, such as tetrahydro-11-deoxycortisol, most consistently distinguished ACC from other adrenal cortical adenomas.
Steroid profiling applications have a long history primarily directed toward diagnosis of endocrine disorders of childhood. Technological advances in mass spectrometry enabling rapid, sensitive, and specific measurements of multiple steroids in biological fluids are now paving the way for numerous other applications, including diagnosis of adrenocortical carcinoma, primary aldosteronism, and different forms of hypercortisolism. Such analytical procedures that target combinations of steroids in a single biological sample have potential for efficient one-shot methods for diagnosis of multiple disorders of steroidogenesis. Moreover, within a specific disorder, such methods can facilitate subtyping for more rapid therapeutic stratification than allowed by current methods that rely on single measurements per sample at sequential time points in a diagnostic process. Combined with advances in computational mathematics, such as machine learning, it is now possible to move from traditional unidimensional approaches for interpreting diagnostic data to methods that can interpret patterns in data. Mass spectrometry–based steroidomics provides an ideal platform for advancing such multidimensional approaches for disease diagnosis and stratification. Bottlenecks that must be overcome to move forward include needs for laboratory harmonization and method certification combined with ingrained reliance on outmoded, but well-accepted, diagnostic methods and general inertia to take advantage of new technologies.
Serum steroid profiling in Cushing's syndrome patients
2019, Journal of Steroid Biochemistry and Molecular Biology
Citation Excerpt :
In recent decades (with improvement of analytical methods) serum measurements are more often used. Low serum adrenal androgens such as DHEAS were repeatedly reported in patients with CS arising from adrenal adenoma, whereas in ACTH-dependent CS, lower aldosterone concentrations were reported [2,6,8]. Low 18-oxo-cortisol was particularly low in ectopic ACTH secreting forms [9].
Cushing’s syndrome is caused by increased exposure to cortisol. Discrimination of different causes of endogenous hypercortisolism can make a diagnostic dilemma.
In serum samples from patients with Cushing’s syndrome (47 with Cushing’s disease, 6 with ectopic ACTH-dependent Cushing’s syndrome, 16 with adrenal adenoma, 7 bilateral adrenal hyperplasia (BMAH) with overt Cushing’s syndrome, 42 controls from the general population) using novel method based on gas chromatography-tandem mass spectrometry (GC–MS/MS) we measured 94 serum steroids to search for steroid fingerprint of each subtype.
Patients with Cushing’s disease and ectopic ACTH producing tumors showed elevated levels of androgens and their metabolites when compared with healthy controls. Mineralocorticoid precursors were also elevated in ectopic ACTH syndrome. The levels of androgens were decreased in adrenal adenomas and BMAH. ROC analysis showed 100% sensitivity and 93.6% specificity for 11β-hydroxyepiandrosterone sulfate for discrimination of Cushing’s disease from ectopic ACTH secretion. We didn’t find any significant (p < 0.05) difference in steroids that would discriminate BMAH from unilateral adenomas causing Cushing’s syndrome.
Various causes of Cushing’s syndrome show particular steroid fingerprints that can be used to discriminate and may help to achieve appropriate clinical diagnosis.
Steroid biomarkers in human adrenal disease
2019, Journal of Steroid Biochemistry and Molecular Biology
Citation Excerpt :
Alternatively, ACTH-dependent CS can result from Cushing disease, meaning an ACTH-secreting pituitary adenoma, from ectopic ACTH secretion, or rarely, from ectopic CRH production [132,133]. Several studies, using plasma or urinary multisteroid profiles, have suggested the release of precursor steroids that could be useful for the differential diagnosis of CS [101,134–137] (Table 1). The first report on the application of LC–MS/MS–based multisteroid profiling in subclinical CS, published in 2015, showed that suppressed adrenal androgens had good accuracy in predicting subclinical hypercortisolism [138].
Adrenal steroidogenesis is a robust process, involving a series of enzymatic reactions that facilitate conversion of cholesterol into biologically active steroid hormones under the stimulation of angiotensin II, adrenocorticotropic hormone and other regulators. The biosynthesis of mineralocorticoids, glucocorticoids, and adrenal-derived androgens occur in separate adrenocortical zones as a result of the segregated expression of steroidogenic enzymes and cofactors. This mini review provides the principles of adrenal steroidogenesis, including the classic and under-appreciated 11-oxygenated androgen pathways. Several adrenal diseases result from dysregulated adrenal steroid synthesis. Herein, we review growing evidence that adrenal diseases exhibit characteristic modifications from normal adrenal steroid pathways that provide opportunities for the discovery of biomarker steroids that would improve diagnosis and monitoring of adrenal disorders.

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Short articleUrinary steroid profile in adrenocortical tumors

Summary

Steroid Biochem Molec Biol

Mol Cell Endocrinol

Mol Cell Endocrinol

Am J Med

Short article
Urinary steroid profile in adrenocortical tumors