scholarly journals Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome

2018 ◽  
Vol 64 (3) ◽  
pp. 586-596 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jimmy Masjkur ◽  
Mirko Peitzsch ◽  
Guido Di Dalmazi ◽  
Martin Bidlingmaier ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Multistep Process ◽  
Steroid Profiles ◽  
Plasma Steroids ◽  
Metabolome Profiling ◽  
Adrenal Disease

Abstract BACKGROUND Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. METHODS In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. RESULTS Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). CONCLUSIONS Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

scholarly journals Plasma Steroid Profiles in Subclinical Compared With Overt Adrenal Cushing Syndrome

2019 ◽  
Vol 104 (10) ◽  
pp. 4331-4340 ◽  
Author(s):  
Jimmy Masjkur ◽  
Matthias Gruber ◽  
Mirko Peitzsch ◽  
Denise Kaden ◽  
Guido Di Dalmazi ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Plasma Concentrations ◽  
Screening Method ◽  
Serum Cortisol ◽  
Dehydroepiandrosterone Sulfate ◽  
Cross Sectional Study ◽  
Biochemical Tests ◽  
Cross Sectional ◽  
Steroid Profiles ◽  
Plasma Steroids

Abstract Context Diagnosis of subclinical adrenal hypercortisolism is based on several tests of the hypothalamic-pituitary-adrenal axis to establish mild alterations of cortisol secretion and dysregulated cortisol physiology. Objective We assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing syndrome (SC). Design Retrospective cross-sectional study. Setting Two tertiary medical centers. Patients Of 208 patients tested for hypercortisolism, disease was excluded in 152 and confirmed in 21 with overt adrenal Cushing syndrome (AC) compared to 35 with SC. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for reference. Main Outcome Measures A panel of 15 plasma steroids was measured by mass spectrometry, with classification by discriminant analysis. Results Patients with SC had lower plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC (P < 0.05). The largest increases (P < 0.001) in plasma steroids among patients with SC were observed for 11-deoxycortisol and 11-deoxycorticosterone. Nevertheless, concentrations of 11-deoxycorticosterone, 11-deoxycortisol, and pregnenolone in patients with AC were higher (P < 0.05) than in those with SC. Patients with SC or AC could be distinguished from subjects without disease using this combination of steroids as precisely as with use of measurements of serum cortisol after administration of dexamethasone. The steroid combination provided superior diagnostic performance compared with each of the other routine biochemical tests. Conclusion Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.

scholarly journals Novel GC-MS/MS Technique Reveals a Complex Steroid Fingerprint of Subclinical Hypercortisolism in Adrenal Incidentalomas

2019 ◽  
Vol 104 (8) ◽  
pp. 3545-3556 ◽  
Author(s):  
Václav Hána ◽  
Jana Ježková ◽  
Mikuláš Kosák ◽  
Michal Kršek ◽  
Václav Hána ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Serum Cortisol ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Urinary Free Cortisol ◽  
Cross Sectional Study ◽  
Adrenal Incidentalomas ◽  
Subclinical Hypercortisolism ◽  
Cross Sectional ◽  
Free Cortisol

AbstractContextImprovement of imaging methods has led to more incidental adrenal tumor findings, especially adenomas. Routine hormonal evaluation uses only a few steroids to evaluate possible hormonal hypersecretion of these adenomas, but a wide spectrum of serum steroid hormone changes has not been published.ObjectiveTo measure the serum levels of 83 steroids from patients with unilateral and bilateral adrenal incidentalomas to uncover full steroid profile changes in patients with subclinical hypercortisolism (SH).DesignCross-sectional study.SettingThe study was conducted at a tertiary inpatient clinic.PatientsFifty-two patients with adrenal incidentalomas (unilateral, n = 29; bilateral, n = 23), including nonfunctioning (n = 11) vs SH (n = 41), and 26 age- and sex-matched controls from the general population were included.Main Outcome MeasuresEighty-three serum steroids were measured by gas chromatography–tandem mass spectrometry (GC-MS/MS) before and after 1 mg dexamethasone, ACTH, midnight serum cortisol, and urinary free cortisol/24 hour.ResultsOf 83 measured steroids, 10 were significantly decreased in patients with SH, including dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate, epiandrosterone sulfate, androstenediol sulfate, conjugated 5α-androstane-3β,17β-diol, and conjugated 5α-androstane-3α,17β-diol. This finding was observed even when unilateral, bilateral, male, and female subgroups were analyzed separately. When we compared routine clinical methods and GC-MS/MS‒measured steroids, the most discriminatory was DHEAS followed by midnight serum cortisol, epiandrosterone sulfate, androsterone sulfate, ACTH, and 16α-hydroxypregnenolone.ConclusionsSH was associated with decreased levels of adrenal androgens, their metabolites, and pregnenolone metabolite. GC-MS/MS is a powerful tool for measuring serum levels of these undescribed changes in steroid metabolism, which are characteristic of SH in adrenal incidentalomas.

scholarly journals Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort

2021 ◽  
Author(s):  
Elena Gonzalez Rodriguez ◽  
Pedro Marques-Vidal ◽  
Bérengère Aubry-Rozier ◽  
Georgios Papadakis ◽  
Martin Preisig ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Salivary Cortisol ◽  
Population Based ◽  
Cross Sectional Study ◽  
Body Composition Assessment ◽  
Cross Sectional ◽  
X Ray ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
The Relationship

AbstractSarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = − 0.153, p < 0.001) and sc-8PM (r = − 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

Paediatric reference range for overnight urinary cortisol corrected for creatinine

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ole D. Wolthers ◽  
Mark Lomax ◽  
Anne Vibeke Schmedes
Keyword(s):  
Mass Spectrometry ◽  
Reference Range ◽  
Inhaled Corticosteroids ◽  
Prediction Interval ◽  
Geometric Mean ◽  
Urinary Free Cortisol ◽  
Urinary Cortisol ◽  
Cross Sectional ◽  
Systemic Activity ◽  
Free Cortisol

Abstract Objectives Systemic activity of inhaled corticosteroids (ICS) may be assessed via urinary cortisol measurement. Overnight urinary free cortisol corrected for creatinine (OUFCC) has been extensively reported in adult studies. However, a paediatric mass spectrometric (MS) reference range for OUFCC is not established. MS methods for OUFCC avoid cross-reactivity with other steroid hormones and are thus preferable to immunoassays. The aim of the present study was to define an MS OUFCC normative range in children. Methods This was a cross-sectional study of healthy pre-pubertal children from 5 to 11 years. Children collected urine from 10 pm or bedtime, whichever was earlier, until 8 am. Urinary free cortisol was measured via a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay (Acquity UPLC with Xevo TQ-S Mass Spectrometer [Waters]) with in-house reagents. Urinary creatinine was measured using a commercial assay (Roche). Results Complete urine collections were obtained from 72 males and 70 females, mean age (SD) 8.6 (1.9) (range 5.0–11.8) years. The OUFCC 95% prediction interval was 1.7–19.8 nmol/mmol. Geometric mean OUFCC was 5.7; range 1.1–24.8 nmol/mmol. Conclusions The obtained normative LC-MS/MS OUFCC reference data facilitate the use of mass spectrometry OUFCC assays in assessment of systemic activity of endogenous and exogenous corticosteroids in children.

Abnormal body composition in patients with adrenal adenomas

2021 ◽  
Author(s):  
Danae Delivanis ◽  
Maria Daniela Hurtado Andrade ◽  
Tiffany Cortes ◽  
Shobana Athimulam ◽  
Aakanksha Khanna ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Muscle Mass ◽  
Visceral Fat ◽  
Cushing Syndrome ◽  
Cross Sectional Study ◽  
Cortisol Secretion ◽  
Muscle Area ◽  
Cross Sectional ◽  
Skeletal Muscle Area

Objective: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease Design: Cross-sectional study, 2014-2018 Methods: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS), and age, sex and body mass index 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal computed tomography imaging. Intraabdominal adipose tissue and muscle mass measurements were performed at the 3rd lumbar spine level. Results: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS and 131 with NFAT. Median age was 56 years (range, 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR) of 2.2 [95% CI 0.9-6.5], 2.0 [1.3-3.2], and 1.8 [1.2-2.7] and a lower skeletal muscle area (OR of 0.01 [95% CI 0-0.09], 0.31 [0.18-0.49], and 0.3 [1.2-2.7]), respectively. For every 1 mcg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P=0.02) and mean total skeletal muscle area decreased by 2.2cm2 (P=0.03). Conclusion: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.

scholarly journals Contralateral adrenal thinning as a distinctive feature of mild autonomous cortisol excess of the adrenal tumors

2020 ◽  
Vol 183 (3) ◽  
pp. 325-333
Author(s):  
Sung Hye Kong ◽  
Jung Hee Kim ◽  
Chan Soo Shin
Keyword(s):  
Adrenal Gland ◽  
Cushing Syndrome ◽  
Volumetric Analysis ◽  
Cross Sectional Study ◽  
Ct Scans ◽  
Adrenal Tumors ◽  
Cross Sectional ◽  
Suppression Test ◽  
The Mean ◽  
Radiologic Features

Objective: To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis. Design: Cross-sectional study. Methods: In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software. Results: The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = −0.583, P < 0.001). Conclusions: The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.

scholarly journals OR03-05 Novel Lipidome Signature in Active Cushing Syndrome Revealed by UHPLC-MS Metabolomics

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arturo Vega-Beyhart ◽  
Marta Iruarrizaga ◽  
Guillermo Garcia-Eguren ◽  
Adriana Pane ◽  
Oriol Giró ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Glutamate Metabolism ◽  
Serum Samples ◽  
Topological Network ◽  
Free Cortisol ◽  
Canonical Pathways ◽  
Omega 6 ◽  
Lipid Metabolites

Abstract Background: Alterations in circulating amino acids, polyamines and acylcarnitines have been reported in patients with endogenous chronic hypercortisolism. However, lipid metabolites profiling and its interplay with the serum metabolome and degree of hypercortisolism in patients with active Cushing syndrome (CS) has not been previously assessed. Objective: To identify new metabolomic biomarkers associated with active CS. Methodology: Multiple UHPLC-MS platforms were used to analyze the metabolome of serum samples obtained from 25 patients with active endogenous CS and 25 controls subjects matched by propensity score (sex, BMI, T2D, DLP, HBP). Results: Metabolome of CS patients was deeply disrupted with 122 (27%) of the assessed metabolites significantly altered (p adj. &lt;0.05) out of which 5 bile acids resulted with the highest perturbation (&gt; 2-fold decrease). From the altered metabolites, 3 amino acids (AA), 2 acylcarnitines (ACs), 2 ceramides (CER) and 5 glycerophospholipids showed direction of effect independently associated with 24-h urinary free cortisol (MS) levels. A highly discriminant (AUC 96%) metabolome signature (n=59) characterized by lower levels of AA, ACs, polyunsaturated fatty acids (PUFA) and monoglycerophosphocolines (MGPC) together with increased levels of triacyclglycerols (TG), CER, diacylglycerophosphocholines (DGPC) and cholesteryl esters was identified and cross-validated (R2Y= 0.92, Q2Y= 0.68) using PLS-DA VIP scores &gt;1.5. PUFA omega-6, and alanine, aspartate and glutamate metabolism resulted the most impacted canonical pathways (q-stat 19.7, 10.8 (p&lt;0.001). Finally, topological network analysis detected 158 pairwise differential correlations (p &lt;0.005, 10,000-fold permutation) between 141 metabolites due to CS where the acylPC (P-18:1/0:0) resulted a key metabolite in the network (betweenness =0.117 & closeness centrality =0.467). Conclusion: Active Cushing syndrome leads to a global proatherogenic shift in the circulating ceramides, glycerophospholipids and sphingolipids metabolites which are independently associated to the levels of urinary free cortisol being potential biomarkers of patients’ cardiovascular risk.

scholarly journals Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study

2016 ◽  
Vol 71 (3) ◽  
Author(s):  
T. T. Tsoriev ◽  
Z. E. Belaya ◽  
L. Y. Rozhinskaya ◽  
G. A. Melnitchenko ◽  
T. A. Grebennikova ◽  
...  
Keyword(s):  
Young Adults ◽  
Grip Strength ◽  
Cushing Syndrome ◽  
Serum Levels ◽  
Serum Samples ◽  
Cross Sectional ◽  
Hand Grip ◽  
Free Cortisol ◽  
The Difference ◽  
Control Study

Background: Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. Aims: To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. Materials and methods: Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. Results: We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1.Conclusions: Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

scholarly journals Urinary sodium is positively associated with urinary free cortisol and total cortisol metabolites in a cross-sectional sample of Australian schoolchildren aged 5–12 years and their mothers

2018 ◽  
Vol 121 (2) ◽  
pp. 164-171
Author(s):  
Susan J. Torres ◽  
Carley Grimes ◽  
Caryl A. Nowson ◽  
Sisitha U. Jayasinghe ◽  
Clinton R. Bruce ◽  
...  
Keyword(s):  
Primary Schools ◽  
Regression Models ◽  
Urinary Free Cortisol ◽  
Linear Regression Models ◽  
Urinary Cortisol ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Potential Impact ◽  
Cortisol Levels ◽  
Cortisol Metabolites

AbstractHigh Na intake and chronically elevated cortisol levels are independently associated with the development of chronic diseases. In adults, high Na intake is associated with high levels of urinary cortisol. We aimed to determine the association between urinary Na and K and urinary cortisol in a cross-sectional sample of Australian schoolchildren and their mothers. Participants were a sample of Australian children (n 120) and their mothers (n 100) recruited through primary schools. We assessed Na, K, free cortisol and cortisol metabolites in one 24 h urine collection. Associations between 24 h urinary electrolytes and 24 h urinary cortisol were assessed using multilevel mixed-effects linear regression models. In children, urinary Na was positively associated with urinary free cortisol (β=0·31, 95 % CI 0·19, 0·44) and urinary cortisol metabolites (β=0·006, 95 % CI 0·002, 0·010). Positive associations were also observed between urinary K and urinary free cortisol (β=0·65, 95 % CI 0·23, 1·07) and urinary cortisol metabolites (β=0·02, 95 % CI 0·03, 0·031). In mothers, urinary Na was positively associated with urinary free cortisol (β=0·23, 95 % CI 0·01, 0·50) and urinary cortisol metabolites (β=0·008, 95 % CI 0·0007, 0·016). Our findings show that daily Na and K intake were positively associated with cortisol production in children and their mothers. Investigation of the mechanisms involved and the potential impact of Na reduction on cortisol levels in these populations is warranted.

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