The diagnostic accuracy of increased late night salivary cortisol for Cushing’s syndrome: a real-life prospective study

Ceccato, Filippo; Marcelli, Giorgia; Martino, Marianna; Concettoni, Carolina; Brugia, Marina; Trementino, Laura; Michetti, Grazia; Arnaldi, Giorgio

doi:10.1007/s40618-018-0921-1

Cited by 30 publications

(14 citation statements)

References 38 publications

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“…We and others have demonstrated that, using relatively nonspecific immunoassays, the sensitivity and specificity of this test exceeds 90% and is as high as 95% to 97% [ 47 , 53 ]. However, these previous studies demonstrating high specificity were generally from referral centers and did not consider the modern liberal use of LNSC as a screening test for CS amongst primary care physicians resulting from the publication of practice guidelines [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…The purpose of the current study was to prospectively evaluate a large number of late-night salivary cortisol samples (N = 1453) obtained from 705 patients with suspected CS. These tests were ordered by endocrinologists, endocrine surgeons, advanced practice providers, and primary care physicians making it more representative of the real world, rather than studies from only tertiary referral centers with a focus on CS [ 47 , 53 , 54 ]. Our approach, therefore, reduced ascertainment bias and gave a more realistic evaluation of the salivary tests.…”

Section: Discussionmentioning

confidence: 99%

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

Kannankeril

Carroll

Findling

et al. 2020

Journal of the Endocrine Society

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Context Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing’s 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 ACTH-independent CS (5 patients with at least one and 11 without any elevated salivary result). In patients with Cushing’s disease (CD), most non-elevated 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’s 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Kannankeril

Carroll

Findling

et al. 2020

Journal of the Endocrine Society

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“…Collecting a sample of salivary cortisol is noninvasive and may be done at home. For this reason, salivary cortisol shows potential as a more valuable screening biomarker of HPA axis dysfunction [ 8 , 9 ]. Dehydroepiandrosterone and DHEA-S are adrenal androgens also used in the assessment of the HPA axis.…”

Section: Discussionmentioning

confidence: 99%

Treatment with Intravenous Methylprednisolone in Patients with Graves’ Orbitopathy Significantly Affects Adrenal Function: Assessment of Serum, Salivary Cortisol and Serum Dehydroepiandrosterone Sulfate

Pelewicz

Szewczyk

Miśkiewicz

2020

JCM

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Treatment of active, moderate-to-severe Graves’ orbitopathy (GO) is the administration of intravenous methylprednisolone (IVMP). IVMP may be followed by additional therapy with oral prednisone. The aim of this study was to analyze the impact of IVMP on adrenal function by evaluation of serum, salivary cortisol and serum dehydroepiandrosterone sulfate (DHEA-S). Fourteen patients received IVMP treatment (cumulative dose of 4.5 g in 12 weekly infusions) followed by oral prednisone (for three months). All patients showed normal adrenal function before the 12th IVMP pulse and one patient was diagnosed with secondary adrenal insufficiency (AI) after prednisone treatment. DHEA-S was significantly lower before the 12th IVMP pulse and after oral prednisone (p = 0.015 and p = 0.00002, respectively) in comparison to evaluation before therapy. DHEA-S levels were below the reference range in one and three patients before the 12th IVMP pulse and after prednisone therapy, respectively. We observed decreased serum (p = 0.05) and salivary (p = 0.011) cortisol levels after oral prednisone therapy in comparison to evaluation before therapy. Treatment with IVMP in a cumulative dose of 4.5 g affects adrenal function, causing more severe impairment of DHEA-S secretion than that of cortisol but does not cause secondary AI. Additional therapy with oral glucocorticoids after IVMP can cause secondary AI.

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“…The hormonal evaluation is necessary in both symptomatic and asymptomatic patients. Demonstration of autonomous, ACTH independent, cortisol secretion follows the recommendation for diagnosis of Cushing syndrome: 1-mg dexamethasone suppression test (1-mg DST), urinary-free cortisol (UFC), and late-night salivary cortisol (LNSC) [23,24]. The indications, evidence, strengths, and limitations of these tests are reviewed in the Endocrine Society Clinical Practice Guidelines [23].…”

Section: Endocrine Workupmentioning

confidence: 99%

“…Post DST cortisol levels between 1.9-5.0 µg/dL should be considered as evidence of possible autonomous cortisol secretion and cortisol levels >5.0 µg/dL should be taken as evidence of autonomous cortisol secretion. Additional biochemical tests to confirm cortisol secretory autonomy and assess the degree of cortisol secretion might be required [24].…”

Section: Endocrine Workupmentioning

confidence: 99%

The Potential of Steroid Profiling by Mass Spectrometry in the Management of Adrenocortical Carcinoma

et al. 2020

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Radiological and endocrinological work up of adrenal neoplasms is aimed at distinguishing between frequent non-functioning adenomas and rare but very aggressive adrenocortical carcinoma (ACC). Relevant research has addressed the identification of molecular, genetic and hormonal markers that could have clinical significance for malignancy, as well as a prognostic value. Regarding endocrine aspects, attention has been paid to the pattern of steroid secretion that can be affected by altered steroidogenic pathway in ACC. The advent of mass spectrometry techniques has overcome many limitations usually associated with immunoassays, allowing the determination of both common and rarely measured steroids in a single analysis with high specificity and sensitivity. Indeed, mass spectrometry strategies may be able to identify an individualized steroid profile of ACC, allowing a rapid diagnosis and a specific follow-up. In this review, insights, strengths and limitations of mass spectrometry-based approaches in steroid profiling, as well as of immunoassay in steroid measurements, will be specifically discussed. Moreover, the latest findings on steroid profiling by mass spectrometry-based techniques, the most promising analytical tool, will be summarized to evaluate if steroid profiling might be the clue for solving the clinical dilemma in differentiating ACC from non-functioning adrenocortical adenomas (ACA).

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The diagnostic accuracy of increased late night salivary cortisol for Cushing’s syndrome: a real-life prospective study

Cited by 30 publications

References 38 publications

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

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

Treatment with Intravenous Methylprednisolone in Patients with Graves’ Orbitopathy Significantly Affects Adrenal Function: Assessment of Serum, Salivary Cortisol and Serum Dehydroepiandrosterone Sulfate

The Potential of Steroid Profiling by Mass Spectrometry in the Management of Adrenocortical Carcinoma

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