scholarly journals Prospective Evaluation of Late-Night Salivary Cortisol and Cortisone by EIA and LC-MS/MS in Suspected Cushing Syndrome

2020 ◽  
Vol 4 (10) ◽  
Author(s):  
Joshua Kannankeril ◽  
Ty Carroll ◽  
James W Findling ◽  
Bradley Javorsky ◽  
Ian L Gunsolus ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Cushing Syndrome ◽  
High Sensitivity ◽  
Lower Sensitivity ◽  
First Line ◽  
Cushing Disease ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Liquid Chromatography Tandem Mass ◽  
Very High

Abstract Context Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing syndrome (CS) with a reported sensitivity and specificity of >90%. However, liquid chromatography-tandem mass spectrometry, validated to measure salivary cortisol (LCMS-F) and cortisone (LCMS-E), has been proposed to be superior diagnostically. Objective, Setting, and Main Outcome Measures Prospectively evaluate the diagnostic performance of EIA-F, LCMS-F, and LCMS-E in 1453 consecutive late-night saliva samples from 705 patients with suspected CS. Design Patients grouped by the presence or absence of at least one elevated salivary steroid result and then subdivided by diagnosis. Results We identified 283 patients with at least one elevated salivary result; 45 had an established diagnosis of neoplastic hypercortisolism (CS) for which EIA-F had a very high sensitivity (97.5%). LCMS-F and LCMS-E had lower sensitivity but higher specificity than EIA-F. EIA-F had poor sensitivity (31.3%) for adrenocorticotropic hormone (ACTH)-independent CS (5 patients with at least 1 and 11 without any elevated salivary result). In patients with Cushing disease (CD), most nonelevated LCMS-F results were in patients with persistent/recurrent CD; their EIA-F levels were lower than in patients with newly diagnosed CD. Conclusions Since the majority of patients with ≥1 elevated late-night salivary cortisol or cortisone result did not have CS, a single elevated level has poor specificity and positive predictive value. LNSC measured by EIA is a sensitive test for ACTH-dependent Cushing syndrome but not for ACTH-independent CS. We suggest that neither LCMS-F nor LCMS-E improves the sensitivity of late-night EIA-F for CS.

scholarly journals Bedtime Salivary Cortisol and Cortisone by LC-MS/MS in Healthy Adult Subjects: Evaluation of Sampling Time

2019 ◽  
Vol 3 (8) ◽  
pp. 1631-1640 ◽  
Author(s):  
Hershel Raff ◽  
Jonathan M Phillips
Keyword(s):  
Salivary Cortisol ◽  
Healthy Adult ◽  
Cushing Syndrome ◽  
Cortisol Awakening Response ◽  
Late Night ◽  
Upper Limit ◽  
Chromatography Tandem Mass Spectrometry ◽  
Late Night Salivary Cortisol ◽  
The Us ◽  
Liquid Chromatography Tandem Mass

AbstractThe measurement of late-night salivary cortisol is a mainstay in the diagnosis of Cushing syndrome. Furthermore, the measurement of salivary cortisol is useful in assessing the cortisol awakening response. Because the salivary glands express 11-β-hydroxysteroid dehydrogenase, the measurement of salivary cortisone may improve the performance of salivary corticosteroid measurements. We measured salivary cortisol by enzyme immunoassay (EIA) and salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in only 50 µL of saliva sampled from 54 healthy subjects (aged 20 to 64 years). We allowed patients to sample at their normal bedtime (2025 to 2400 hours) to answer a common question as to whether sampling at the normal bedtime is equivalent to the standard required sampling at 2300 to 2400 hours. We found that the salivary cortisol and cortisone results by LC-MS/MS correlated well with salivary cortisol measured with the US Food and Drug Administration-cleared EIA. Furthermore, the upper limit of normal of salivary cortisol by EIA for bedtime samples was lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours. There were no significant effects of age or sex on any of the salivary steroid measurements. We conclude that (i) salivary cortisol and cortisone can be reliably measured by LC-MS/MS in small volumes of saliva and (ii) that patients can be evaluated using saliva sampled at their normal bedtime, rather than being required to stay awake until 2300 to 2400 hours.

scholarly journals Screening and diagnosis of Cushing's syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1191-1198 ◽  
Author(s):  
Margaret de Castro ◽  
Ayrton C. Moreira
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Linear Growth ◽  
Fat Distribution ◽  
Cushing's Syndrome ◽  
First Line ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol ◽  
Pituitary Adrenal Axis

Cushing's syndrome (CS) results from sustained pathologic hypercortisolism. The clinical features are variable and the most specific features for CS include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Clinical presentation of CS can be florid and in this case the diagnosis is usually straightforward. However, the diagnosis can be difficult particularly in states of mild or cyclical or periodical hypercortisolism. Several tests based on the understanding of the physiologic characteristics of the hypothalamic-pituitary-adrenal axis have been used extensively to confirm the diagnosis of Cushing's syndrome, but none has proven fully capable of distinguishing all cases of CS from normal and/or pseudo-Cushing individuals. Three first-line diagnostic tests are currently used to screen for CS: measurement of free cortisol in 24-hour urine (UFC), cortisol suppressibility by low doses of dexamethasone (DST), and assessment of cortisol circadian rhythm using late-night serum and/or salivary cortisol. This paper discusses the effectiveness regarding best cut-off values, the sensitivity and the specificity of these tests to screen for CS. Late-night salivary cortisol appears to be the most useful screening test. UFC and DST should be performed to provide further confirmation of the diagnosis.

Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults

2017 ◽  
Vol 55 (12) ◽  
Author(s):  
Sabrina Coelli ◽  
Camila Bergonsi Farias ◽  
Ariana Aguiar Soares ◽  
Gabriele Martins Crescente ◽  
Vânia Naomi Hirakata ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Salivary Cortisol ◽  
Cushing Syndrome ◽  
Reference Value ◽  
Healthy Adults ◽  
Healthy Population ◽  
Cross Sectional ◽  
Late Night ◽  
Late Night Salivary Cortisol

AbstractBackground:Late-night salivary cortisol (LNSC) is one of the most reliable tests to screen for endogenous Cushing syndrome. This test is simple, inexpensive and noninvasive and has high sensitivity and specificity. The aim of our study was to analyze the putative influence of age, gender and body mass index (BMI) on LNSC levels in a healthy population.Methods:Cross-sectional study conducted in healthy adults. Midnight saliva samples were collected at home. Participants refrained from teeth brushing, eating or drinking for 2 h prior to collection. Salivary cortisol measured by electrochemiluminescence immunoassay (ECLIA). The study was approved by the Ethics Committee of the hospital (number 140073).Results:We evaluated 122 nonsmoking healthy volunteers. Mean age was 35±14 years (range, 18–74 years); 63% were women. Mean BMI was 24±3 kg/mConclusions:The maximum reference value (P97.5) of LNSC was set at 8.3 nmol/L (0.3 μg/dL) using ECLIA. Advanced age was associated with higher LNSC levels, with no evident influence of gender or BMI.

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.

Late-Night Salivary Cortisol for the Diagnosis of Cushing Syndrome: A Meta-Analysis

2009 ◽  
Vol 15 (4) ◽  
pp. 335-342 ◽  
Author(s):  
Ty Carroll ◽  
Hershel Raff ◽  
James Findling
Keyword(s):  
Salivary Cortisol ◽  
Cushing Syndrome ◽  
Meta Analysis ◽  
Late Night ◽  
Late Night Salivary Cortisol

Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing’s syndrome: results of a single-center 7-year experience

2018 ◽  
Vol 67 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Nusret Yilmaz ◽  
Gokhan Tazegul ◽  
Humeyra Bozoglan ◽  
Ramazan Sari ◽  
Sebahat Ozdem ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Diagnostic Performance ◽  
Cushing's Syndrome ◽  
Lower Sensitivity ◽  
Subclinical Cushing’S Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing’s syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing’s syndrome (CCS) and subclinical Cushing’s syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing’s syndrome (NoCS). The cause of the Cushing’s syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107–33) µg/dL in CCS group, 0.398 (0.16–1.02) µg/dL in SCS group, and 0.18 (0.043–0.481) µg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 µg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 µg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing’s syndrome.

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