scholarly journals SAT-166 Advantage and Trustworthy of Cortisol and Dexamethasone Evaluation in Different Biological Matrices in Patients with Adrenal Masses

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luana Lionetto ◽  
Roberta Maggio ◽  
Pina Lardo ◽  
Donatella De Bernardini ◽  
Fabiola Cipolla ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Reference Ranges ◽  
Serum Samples ◽  
Late Night ◽  
Liquid Chromatography Tandem Mass ◽  
Adrenal Masses ◽  
Suppression Test ◽  
The Individual

Abstract Biochemical function of adrenal masses is currently based on 1mg post-overnight dexamethasone suppression test (pDST). Several approaches are recently developed, in order to reduce false positive/negative samples, only in retrospective series. They are based on the correlation of some different parameters, i.e. late-night salivary cortisol (LNSC) vs serum and salivary cortisol pDST; LNSC vs serum and salivary cortisol and serum dexamethasone pDST; LNSC and cortisone vs serum cortisol and salivary cortisol and cortisone pDST. Although these findings offer a better diagnostic performance, several conditions are still disappointed. No information is traceable about the harvest time of diurnal salivary and serum samples and no study include neither the levels of salivary nor urinary dexamethasone pDST. Aim of our study is to combine all these strategies in order to avoid the underestimated biases and obtain more precise information about the true “cortisol condition” of the patients. To reach this purpose we assess both cortisol and dexamethasone concentrations in several samples: saliva at 11PM before the drug administration, diurnal saliva and serum at 8AM and also the urine collection from 11PM to 8AM. Analytes levels are measured using a validated liquid chromatography-tandem mass spectrometry method. In this study we included 20 subjects without morphological adrenal alteration (MRI assessment), dyslipidemia, hypertension and impaired glucose tolerance (healthy controls) and 20 patients with adrenal incidentaloma showing different cortisol levels ranging from normal to ACTH-independent hypercortisolism. In both series, LNSC were similar to salivary cortisol pDST, even if they were greater in the patients with adrenal incidentalomas and subclinical cortisol secretion. Serum dexamethasone levels were in reference ranges, while salivary and urinary dexamethasone found in these matrices require additional sample numbers in order to establish appropriate cut-offs. Our preliminary results suggest that the combination of these findings could represent an improvement to assess the individual cortisol status.

scholarly journals Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

2020 ◽  
Vol 17 (1) ◽  
pp. 13-21
Author(s):  
Zhanna E. Belaya ◽  
Anastasia A. Malygina ◽  
Tatiana A. Grebennikova ◽  
Aleksandr V. Il'yin ◽  
Liudmila Ya. Rozhinskaya ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Dexamethasone Suppression Test ◽  
Histological Evaluation ◽  
Diagnostic Study ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushings syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive. AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA). MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushings Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushings syndrome manifestation. RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,512,7 nmol/l (595 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST 0,838 (95% СI 0,7720,905), for blood cortisol in 1-mg DST 0,965 (95% CI 0,9390,992) and for late-night salivary cortisol 0,925 (95% CI 0,8820,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA. CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity.

scholarly journals The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma

2009 ◽  
Vol 160 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Benedetta Masserini ◽  
Valentina Morelli ◽  
Silvia Bergamaschi ◽  
Federica Ermetici ◽  
Cristina Eller-Vainicher ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Salivary Cortisol ◽  
Adrenal Incidentaloma ◽  
Urinary Free Cortisol ◽  
Standard Test ◽  
Subclinical Hypercortisolism ◽  
Late Night ◽  
Free Cortisol ◽  
Suppression Test

ObjectiveThe criteria for defining subclinical hypercortisolism (SH) are debated and a real gold standard test or combination of tests is lacking. Recently, late-night salivary cortisol (MSC) has been described as a sensitive and easy-to-perform marker for diagnosing overt hypercortisolism. No data are available on the role of MSC in the diagnosis of SH. The aim of this study was to evaluate the sensitivity and specificity of MSC levels in the diagnosis of SH in patients with adrenal incidentalomas (AI).MethodsIn 103 (females/males, 69/34) patients with AI, MSC levels were studied. One milligram overnight dexamethasone suppression test (DST), urinary-free cortisol (UFC), and ACTH plasma levels were also evaluated. Patients were defined as affected by SH if they showed two of the following criteria: DST>83 nmol/l, ACTH <2.2 pmol/l, and UFC >193 nmol/24 h.ResultsNo difference in MSC levels in patients with SH (3.1±3.1 nmol/l) compared with patients without SH (2.2±2.8 nmol/l) was observed. In patients with SH, MSC levels were significantly correlated with DST (r=0.4,P<0.05). Using the cut-off of 5.1 nmol/l, the sensitivity and specificity of MSC levels for diagnosis of SH is 22.7 and 87.7% respectively.ConclusionIn patients with AI, normal levels of MSC do not exclude SH, whereas high levels may suggest the presence of SH identified by conventional tests. Thus, MSC is not suitable as a screening test, although it may be used in conjunction with other tests as the confirming test in selected patients.

scholarly journals The Influence of Serum Sample Storage Conditions on Selected Laboratory Parameters Related to Oxidative Stress: A Preliminary Study

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 51
Author(s):  
Lilla Pawlik-Sobecka ◽  
Katarzyna Sołkiewicz ◽  
Izabela Kokot ◽  
Aleksandra Kiraga ◽  
Sylwia Płaczkowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serum Sample ◽  
Storage Conditions ◽  
Wilcoxon Test ◽  
Reference Ranges ◽  
Sample Storage ◽  
Serum Samples ◽  
The Stability ◽  
The Individual ◽  
The Impact

The present work aims at accessing the stability of biological material stored for diagnostic and scientific purposes. The influence of the temperature, storage time, and cyclic thawing on concentration stability of selected oxidative stress parameters in human serum was investigated. The study group consisted of 20 serum samples collected from healthy volunteers aged 18–52. The parameters whose reference ranges were not determined and to which validated determination methods did not correspond were examined by manual methods (FRAP and AOPP). Automatic methods were used to determine routine laboratory tests (albumin, total protein, bilirubin, uric acid) using the Konelab 20i® analyzer. The samples were stored at various temperatures (room temperature, 4 °C, −20 °C, −80 °C) for max 6 months and were subjected to cyclic thawing at 1 month intervals. In order to check whether any differences between the concentrations of the studied parameters existed when the samples were stored in various conditions, the paired Student t-test or Wilcoxon test and comparison to desirable bias were applied. Based on the obtained results, it was found that the temperature and time of serum sample storage significantly affected the stability of the analyzed parameters and determined different shelf lives of serum samples for oxidative stress examination. Therefore, continuing the investigation concerning the impact of storage conditions on various serum parameters seems justified due to the discrepancy between the individual results obtained by different researchers and the inconsistencies between the results of scientific research and the applicable recommendations.

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

2016 ◽  
Vol 175 (2) ◽  
pp. G1-G34 ◽  
Author(s):  
Martin Fassnacht ◽  
Wiebke Arlt ◽  
Irina Bancos ◽  
Henning Dralle ◽  
John Newell-Price ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Adrenal Mass ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Adrenal Masses ◽  
Autonomous Cortisol Secretion

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 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing’s syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/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 with 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 incidentalomas

Comparison of 1 mg versus 2 mg Dexamethasone Suppression Test in Patients with Obesity

2017 ◽  
Vol 49 (11) ◽  
pp. 854-859
Author(s):  
Sandrine Urwyler ◽  
Nina Cupa ◽  
Mirjam Christ-Crain
Keyword(s):  
Salivary Cortisol ◽  
False Positive ◽  
False Positive Rate ◽  
Serum Cortisol ◽  
Dexamethasone Suppression Test ◽  
Obese Patients ◽  
Positive Rate ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

AbstractIn this study, we compared the 2 mg dexamethasone suppression test (DST) with the gold-standard 1 mg DST in obese patients in order to reduce the false-positive rate for Cushing’s syndrome (CS). The primary endpoint was the comparison of serum cortisol levels after 1 mg versus 2 mg DST in patients with a BMI >30 kg/m2 and at least one additional feature of the metabolic syndrome. Secondary endpoints were comparison of salivary cortisol and ACTH levels, respectively. Fifty-four obese patients were included. Median serum cortisol levels after 1 mg DST and 2 mg DST were similar [28 nmol/l (20; 36) vs. 28 nmol/l (20; 38), p=0.53]. Salivary cortisol was 8.2 nmol/l (4.7; 11.7) after the 1 mg DST vs. 6.7 nmol/l (4.2; 9.5) after the 2 mg test, p=0.09. ACTH levels were higher after the 1 mg DST compared to the 2 mg DST [10.0 pg/ml (7.6; 10.7) vs. 5.0 pg/ml (5.0; 5.1), p<0.0001]. The false positive rate after the 1 mg DST was 14.8% (n=8) and was reduced to 11.1% (n=6) after the 2 mg DST. All non-suppressors (n=8) had type 2 diabetes and most of them took a medication interacting with cytochrome P450 3A4 (CYP3A4). In individuals with obesity, the 2 mg DST was not superior to the 1 mg DST in regard to serum cortisol levels. However, in some patients, particularly with poorly controlled diabetes or medication interacting with CYP3A4 and without adequate suppression after the 1 mg DST, the 2 mg DST might prove helpful to reduce the false-positive rate for CS. ClinicalTrials.gov Number: NCT02227420

scholarly journals Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism

2021 ◽  
Vol 53 (10) ◽  
pp. 662-671
Author(s):  
Lukas van Baal ◽  
Marc Wichert ◽  
Denise Zwanziger ◽  
Henning Dralle ◽  
Frank Weber ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Salivary Cortisol ◽  
Cushing's Disease ◽  
Control Group ◽  
High Morbidity ◽  
Reference Ranges ◽  
Ectopic Acth ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Ectopic Acth Production

AbstractDue to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing’s disease and Cushing’s disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.

scholarly journals The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk

2019 ◽  
Vol 104 (11) ◽  
pp. 5519-5528 ◽  
Author(s):  
Guido Di Dalmazi ◽  
Flaminia Fanelli ◽  
Guido Zavatta ◽  
Silvia Ricci Bitti ◽  
Marco Mezzullo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
University Hospital ◽  
Adrenal Tumors ◽  
Adrenal Incidentalomas ◽  
Steroid Profiling ◽  
Liquid Chromatography Tandem Mass ◽  
Steroid Profiles ◽  
Adrenal Masses ◽  
Suppression Test ◽  
Autonomous Cortisol Secretion

Abstract Context Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors. Objectives To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS). Design Cohort study. Setting University hospital. Patients Patients (n = 302) with incidentally discovered adrenal masses, divided into unilateral adenoma and hyperplasia with ACS (n = 46 and n = 52, respectively) and NS (n = 120 and n = 84, respectively). Post–dexamethasone suppression test (DST) cortisol <50 or >50 nmol/L defined NS and ACS, respectively. Intervention Analysis of 10-steroid panel by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months). Main Outcome Measures Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile. Results Patients with unilateral adenomas and ACS showed higher cortisol, 11-deoxycortisol, and corticosterone and lower dehydroepiandrosterone than those with NS adenomas. Patients with ACS hyperplasia showed higher cortisol and lower androgens in women than those with NS. Patients with ACS had reduced suppression of post-DST cortisol, 11-deoxycortisol, and corticosterone, irrespective of adrenal morphology. Post-DST cortisol and corticosterone were associated with higher prevalence of severe/resistant hypertension. Patients with ACS unilateral adenomas showed higher incidence of worsening of hypertensive disease and novel cardiovascular events than those with NS, with post-DST cortisol [hazard ratio (HR) 1.02; 95% CI, 1.01 to 1.03; P < 0.001] and baseline corticosterone (HR 1.06; 95% CI, 1.01 to 1.12; P = 0.031) among the main predictors. Conclusions Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.

scholarly journals Midnight Salivary Cortisol Versus Urinary Free and Midnight Serum Cortisol as Screening Tests for Cushing’s Syndrome

2003 ◽  
Vol 88 (9) ◽  
pp. 4153-4157 ◽  
Author(s):  
Pietro Putignano ◽  
Paola Toja ◽  
Antonella Dubini ◽  
Francesca Pecori Giraldi ◽  
Salvatore Maria Corsello ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Diagnostic Performance ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Screening Tests ◽  
Late Night ◽  
Free Cortisol ◽  
Simple Obesity

The diagnosis of Cushing’s syndrome (CS) is often a challenge. Recently, the determination of late night salivary cortisol levels has been reported to be a sensitive and convenient screening test for CS. However, no studies have included a comparison with other screening tests in a setting more closely resembling clinical practice, i.e. few patients with CS to be distinguished from patients with pseudo-Cushing states (PC), including the large population of obese patients. The aim of this study was to compare the diagnostic performance of midnight salivary cortisol (MSC) measurement with that of midnight serum cortisol (MNC) and urinary free cortisol (UFC) in differentiating 41 patients with CS from 33 with PC, 199 with simple obesity, and 27 healthy normal weight volunteers. Three patients with CS had MSC levels lower than the cut-off point derived from receiver operator characteristic analysis (9.7 nmol/liter), yielding a sensitivity for this parameter of 92.7%. In the whole study population, no statistically significant differences in terms of sensitivity, specificity, diagnostic accuracy, and predictive values were observed among tests. In particular, the overall diagnostic accuracy for MSC (93%; 95% confidence interval, 90.1–95.9%) was similar to those of UFC (95.3%; 94.1–96.5%) and MNC (95.7%; 93.4–98%; both P = NS). The diagnostic performance of MSC was superimposable to that of MNC also within the area of overlap in UFC values (≤569 nmol/24 h) between CS and PC. In conclusion, MSC measurement can be recommended as a first-line test for CS in both low risk (simple obesity) and high-risk (i.e. PC) patients. Given its convenience, this procedure can be added to tests traditionally used for this purpose, such as UFC and MNC.

scholarly journals Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency

2013 ◽  
Vol 169 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Filippo Ceccato ◽  
Mattia Barbot ◽  
Marialuisa Zilio ◽  
Sergio Ferasin ◽  
Gianluca Occhi ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Healthy Subjects ◽  
Adrenal Incidentaloma ◽  
High Sensitivity ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol

ObjectiveSalivary cortisol has recently been suggested for studies on the hypothalamic–pituitary–adrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing's syndrome (CS), and some authors have reported that low salivary cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of salivary cortisol in specific diagnostic settings of HPA axis disease.Subjects and methodsWe analyzed morning salivary cortisol (MSC) and late-night salivary cortisol (LNSC) levels in 406 subjects: 52 patients with Cushing's disease (CD), 13 with ectopic CS, 17 with adrenal CS, 27 with CD in remission (a mean follow-up of 66±39 months), 45 with adrenal incidentaloma, 73 assessed as having CS and then ruled out for endogenous hypercortisolism, 75 with adrenal insufficiency, and 104 healthy subjects.ResultsA LNSC value above 5.24 ng/ml differentiated CS patients from controls with high sensitivity (96.3%) and specificity (97.1%); we found higher LNSC levels in ectopic CS patients than in CD patients. We found no difference in MSC and LNSC levels between patients with CD in remission and healthy subjects. Both MSC and LNSC levels were higher in patients with adrenal incidentaloma than in healthy controls. A MSC value below 2.65 ng/ml distinguished patients with adrenal insufficiency from controls with high sensitivity (97.1%) and specificity (93.3%).ConclusionsSalivary cortisol is a useful tool to assess endogenous cortisol excess or adrenal insufficiency and to evaluate stable CD in remission.

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