scholarly journals Late-Night Salivary Cortisol as a Screening Test for Cushing’s Syndrome1

1998 ◽  
Vol 83 (8) ◽  
pp. 2681-2686 ◽  
Author(s):  
Hershel Raff ◽  
Jonathan L. Raff ◽  
James W. Findling
Keyword(s):  
Clinical Features ◽  
Cushing’S Syndrome ◽  
Diurnal Rhythm ◽  
Salivary Cortisol ◽  
Screening Test ◽  
Plasma Cortisol ◽  
Normal Subjects ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol

abstract The clinical features of Cushing’s syndrome (such as obesity, hypertension, and diabetes) are commonly encountered in clinical practice. Patients with Cushing’s syndrome have been identified by an abnormal low-dose dexamethasone suppression test, elevated urine free cortisol (UFC), an absence of diurnal rhythm of plasma cortisol, or an elevated late-night plasma cortisol. Because the concentration of cortisol in the saliva is in equilibrium with the free (active) cortisol in the plasma, measurement of salivary cortisol in the evening (nadir) and morning (peak) may be a simple and convenient screening test for Cushing’s syndrome. The purpose of this study was to evaluate the usefulness of the measurement of late-night and morning salivary cortisol in the diagnosis of Cushing’s syndrome. We studied 73 normal subjects and 78 patients referred for the diagnosis of Cushing’s syndrome. Salivary cortisol was measured at 2300 h and 0700 h using a simple, commercially-available saliva collection device and a modification of a standard cortisol RIA. In addition, 24-h UFC was measured within 1 month of saliva sampling. Patients with proven Cushing’s syndrome (N = 39) had significantly elevated 2300-h salivary cortisol (24.0 ± 4.5 nmol/L), as compared with normal subjects (1.2 ± 0.1 nmol/L) or with patients referred with the clinical features of hypercortisolism in whom the diagnosis was excluded or not firmly established (1.6± 0.2 nmol/L; N = 39). Three of 39 patients with proven Cushing’s had 2300-h salivary cortisol less than the calculated upper limit of the reference range (3.6 nmol/L), yielding a sensitivity of 92%; one of these 3 patients had intermittent hypercortisolism, and one had an abnormal diurnal rhythm (salivary cortisol 0700-h to 2300-h ratio <2). An elevated 2300-h salivary cortisol and/or an elevated UFC identified all 39 patients with proven Cushing’s syndrome (100% sensitivity). Salivary cortisol measured at 0700 h demonstrated significant overlap between groups, even though it was significantly elevated in patients with proven Cushing’s syndrome (23.0 ± 4.2 nmol/L), as compared with normal subjects (14.5± 0.8 nmol/L) or with patients in whom Cushing’s was excluded or not firmly established (15.3 ± 1.5 nmol/L). Late-night salivary cortisol measurement is a simple and reliable screening test for spontaneous Cushing’s syndrome. In addition, late-night salivary cortisol measurements may simplify the evaluation of suspected intermittent hypercortisolism, and they may facilitate the screening of large high-risk populations (e.g. patients with diabetes mellitus).

scholarly journals Late-night Salivary Cortisol as A Screening Test for the Diagnosis of Cushing's Syndrome in Japan

2008 ◽  
Vol 55 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Masaru DOI ◽  
Naoko SEKIZAWA ◽  
Yuji TANI ◽  
Kyoichiro TSUCHIYA ◽  
Ryuji KOUYAMA ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Screening Test ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol

scholarly journals Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing’s Syndrome in a Portuguese Population

2019 ◽  
Vol 32 (5) ◽  
pp. 381 ◽  
Author(s):  
Adriana De Sousa Lages ◽  
João Gonçalo Frade ◽  
Diana Oliveira ◽  
Isabel Paiva ◽  
Patrícia Oliveira ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Operating Characteristic ◽  
Screening Tool ◽  
Characteristic Curve ◽  
Normal Subjects ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Late Night Salivary Cortisol

Introduction: Diagnosis of Cushing’s syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined.Material and Methods: Three groups of subjects were studied: normal subjects, suspected and proven Cushing’s syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden’s J index.Results: We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing’s syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing’s syndrome group.Discussion: The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing’s syndrome (0.6798 ± 0.52 μg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity and specificity.Conclusion: Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism.

Pitfalls in the diagnosis and management of Cushing's syndrome

2015 ◽  
Vol 38 (2) ◽  
pp. E4 ◽  
Author(s):  
Vivek Bansal ◽  
Nadine El Asmar ◽  
Warren R. Selman ◽  
Baha M. Arafah
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Salivary Cortisol ◽  
Clinical Symptoms ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Biochemical Tests ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone–secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

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.

scholarly journals A commentary on Diagnosing Cushing’s disease in the context of renal failure

2019 ◽  
Vol 181 (4) ◽  
pp. C9-C11
Author(s):  
Hershel Raff ◽  
Eric P Cohen ◽  
James W Findling
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Cushing’S Syndrome ◽  
Salivary Cortisol ◽  
Cushing's Syndrome ◽  
Late Night ◽  
Urine Free Cortisol ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol ◽  
Pituitary Adrenal Axis

The diagnosis of endogenous hypercortisolism (Cushing's syndrome) is extremely challenging. Chronic kidney disease (CKD) increases the activity of the hypothalamic-pituitary-adrenal axis making the diagnosis of Cushing's syndrome even more challenging. This is particularly so since urine free cortisol (UFC) testing is not useful in CKD. The case report by Stroud et al. in this issue of the European Journal of Endocrinology highlights this problem by finding normal UFC in a patient with pituitary ACTH-dependent Cushing's syndrome. Elevated late-night salivary cortisol (LNSC) testing was diagnostic and pituitary adenomectomy was curative. LNSC measurement is the diagnostic test of choice in patients with suspected Cushing's syndrome, particularly in the presence of CKD..

Sign in / Sign up

Export Citation Format

Share Document