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Cited by 129Pituitary Gland Disorders and TreatmentsAdrenal and Paraganglionic TumorsAdrenal Hormones and Disorders

Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients

Nunes, Marie-Laure, Vattaut, Stéphanie, Corcuff, Jean-Benoît, Rault, Alexandre, Loiseau, Hugues, Gatta, Blandine, Valli, Nathalie, Letenneur, Luc +1 more·2009·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2008-1542
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Abstract

CONTEXT: Neither precise evaluation of pertinent thresholds nor comparison of the diagnostic performance of late-night salivary cortisol (NSC) between inpatient and outpatient settings has been conducted. The usefulness of NSC for the screening of "subclinical" Cushing's syndrome is still unknown. OBJECTIVES: The aim of the study was to compare the influence of inpatient and outpatient settings on the diagnostic performance of NSC and assess its usefulness as a screening test for subclinical Cushing's syndrome. DESIGN: Consecutive patients were investigated prospectively with two salivary collections, first as inpatients and then as outpatients. PARTICIPANTS: Forty-two obese subjects participated in the study, as well as nine patients cured of Cushing's disease, 13 with overt Cushing's syndrome, 14 showing mild recurrence of Cushing's disease, and 48 with adrenal incidentalomas [23 subclinical cortisol-secreting adenomas (SCSA), 25 nonsecreting adenomas]. MAIN OUTCOME MEASURES: Reproducibility of NSC and diagnostic performance were measured using receiver operating characteristic analysis. RESULTS: NSC in controls was similar between inpatient and outpatient settings. The diagnostic performance of NSC across the different patient groups was similar irrespective of the setting. A threshold of 12 nmol/liter yielded 100% sensitivity and specificity in overt Cushing's syndrome. Optimal performance in subclinical Cushing's syndrome required lower thresholds. NSC showed acceptable performance in diagnosing recurrence of Cushing's disease (90% sensitivity, 91.8% specificity). On the contrary, NSC was similar between patients with SCSA and nonsecreting adenomas. CONCLUSIONS: Our data validate the outpatient bed sampling strategy for NSC with no need for specific outpatient threshold. NSC may be helpful to detect mild recurrence of Cushing's disease after surgery but is of little value in identifying SCSA amongst adrenal incidentalomas.

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  • Most studies have found that late-night salivary cortisol (LNSC), regardless of assay method, has poor sensitivity in patients with mild cortisol excess (formerly subclinical Cushing syndrome).

    “most studies have found that LNSC (regardless of assay method) has a poor sensitivity in patients with mild cortisol excess (formerly known as subclinical CS) [20, 56, 62-76]”

    From Prospective Evaluation of Late-Night Salivary Cortisol and Cortisone by EIA and LC-MS/MS in Suspected Cushing Syndrome (2020) · cites this paper as [67]

    The Results section reports poor performance for detecting subclinical cortisol-secreting adenomas, with sensitivity around 77%, and the Discussion says salivary cortisol has limitations in subclinical Cushing’s syndrome. But sensitivity for mild recurrence of Cushing’s disease was 84.6–90%, and this paper does not establish that poor sensitivity holds regardless of assay method or across most studies. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Some authors found low sensitivity of midnight salivary cortisol for identifying subclinical hypercortisolism, whereas others found that consistent or frequent elevations may indicate the condition.

    “Some authors found a low sensitivity of MSaC in identifying SH (31,32), whereas others showed that subjects with either consistent or frequent elevations of this parameter may actually have SH (69).”

    From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [31]

  • In studies using arbitrarily defined biochemical criteria as the gold standard, HPA axis parameters showed good specificity (90-98% using 1-mg DST) but generally poor sensitivity (41-86% using ACTH).

    “Overall, in these studies, the different parameters showed a good specificity (90 -98%, using 1-mg DST) but, generally, a poor sensitivity (41-86% using ACTH levels).”

    From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [31]

  • Altered circadian rhythm and urinary free cortisol levels were not sensitive enough for diagnosing subclinical hypercortisolism.

    “The altered circadian rhythm, evaluated by either MSaC or MSeC, and UFC levels were not found to be sensitive enough for diagnosing SH (31,32).”

    From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [31]

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Authors
Nunes, M.-L., Vattaut, S., Corcuff, J.-B., Rault, A., Loiseau, H., Gatta, B., Valli, N., Letenneur, L., & Tabarin, A.
Affiliations
Inserm (FR)
Corresponding author
Tabarin, Antoine
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2009-02
Volume
94
Issue
2
Pages
456-462
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2008-1542
OpenAlex
W1969322965
Cited by
129
References
43
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 9 · 2012: 11
FWCI
10.40
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
late-night salivary cortisol, subclinical Cushing's syndrome, adrenal incidentaloma, diagnostic thresholds, screening test performance, obesity
MeSH terms
Adrenal Cortex Neoplasms, Ambulatory Care, Circadian Rhythm, Cushing Syndrome, Female, Hospitalization, Humans, Hydrocortisone, Inpatients, Male, Outpatients, Recurrence, Saliva, Sensitivity and Specificity, Time Factors, Case-Control Studies, Adrenocortical Adenoma, Incidental Findings

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