Utility of Salivary Cortisol Measurements in Cushing's Syndrome and Adrenal Insufficiency

Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Milwaukee, Wisconsin 53215, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 07/2009; 94(10):3647-55. DOI: 10.1210/jc.2009-1166
Source: PubMed

ABSTRACT The measurement of cortisol in saliva is a simple, reproducible, and reliable test to evaluate the normal and disordered control of the hypothalamic-pituitary-adrenal (HPA) axis. There are a variety of simple methods to obtain saliva samples without stress, making this a robust test applicable to many different experimental and clinical situations.
Ovid Medline and PubMed from 1950 to present were searched using the following strategies: [ and and<Cushing or Cushing's>] and [ and and<adrenal insufficiency or hypoadrenalism or hypopituitarism or Addison's disease>]. The bibliographies of all relevant citations were evaluated for any additional appropriate citations.
Measurement of an elevated late-night (2300 to 2400 h) salivary cortisol has a greater than 90% sensitivity and specificity for the diagnosis of endogenous Cushing's syndrome. Late-night salivary cortisol measurements are also useful to monitor patients for remission and/or recurrence after pituitary surgery for Cushing's disease. Because it is a surrogate for plasma free cortisol, the measurement of salivary cortisol may be useful during an ACTH stimulation test in patients with increased plasma binding protein concentrations due to increased estrogen, or decreased plasma binding protein concentrations during critical illness. Most reference laboratories now offer salivary cortisol testing.
It is expected that the use of the measurement of salivary cortisol will become routine in the evaluation of patients with disorders of the HPA axis.

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    • "Each week, for the measurement of biologically active free cortisol (Raff 2009), study participants passively collected saliva by not swallowing for 1–2 min and drooling through a straw. The samples were transported on ice to the clinic, stored at À80°C, and assayed for saliva cortisol using a commercially available ELISA kit (IBL International Corp., Toronto, Ontario, Canada). "
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    ABSTRACT: Biomarkers of chronic cell hydration status are needed to determine whether chronic hyperosmotic stress increases chronic disease risk in population-representative samples. In vitro, cells adapt to chronic hyperosmotic stress by upregulating protein breakdown to counter the osmotic gradient with higher intracellular amino acid concentrations. If cells are subsequently exposed to hypo-osmotic conditions, the adaptation results in excess cell swelling and/or efflux of free amino acids. This study explored whether increased red blood cell (RBC) swelling and/or plasma or urine amino acid concentrations after hypo-osmotic challenge might be informative about relative chronic hyperosmotic stress in free-living men. Five healthy men (20-25 years) with baseline total water intake below 2 L/day participated in an 8-week clinical study: four 2-week periods in a U-shaped A-B-C-A design. Intake of drinking water was increased by +0.8 ± 0.3 L/day in period 2, and +1.5 ± 0.3 L/day in period 3, and returned to baseline intake (0.4 ± 0.2 L/day) in period 4. Each week, fasting blood and urine were collected after a 750 mL bolus of drinking water, following overnight water restriction. The periods of higher water intake were associated with significant decreases in RBC deformability (index of cell swelling), plasma histidine, urine arginine, and urine glutamic acid. After 4 weeks of higher water intake, four out of five participants had ½ maximal RBC deformability below 400 mmol/kg; plasma histidine below 100 μmol/L; and/or undetectable urine arginine and urine glutamic acid concentrations. Work is warranted to pursue RBC deformability and amino acid concentrations after hypo-osmotic challenge as possible biomarkers of chronic cell hydration.
    10/2013; 1(5):e00117. DOI:10.1002/phy2.117
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    • "Cushing’s syndrome is one of the most difficult endocrinopathies to diagnose, and for this reason researchers around the world have a keen interest in discovering a more efficient early diagnostic method (17,18). Diagnostic trials recommended by the Endocrine Society are: 24-hour urinary free cortisol, dexamethasone suppression test – 1mg oral at night and late-night salivary cortisol (17). "
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    ABSTRACT: There is a growing interest in diagnosis based on the analysis of saliva. This is a simple, non-invasive method of obtaining oral samples which is safe for both the health worker and the patient, not to mention allowing for simple and cost-efficient storage. The majority of studies use general saliva samples in their entirety, complex fluids containing both local and systemic sources and whose composition corresponds to that of the blood. General saliva contains a considerable amount of desquamated epithelial cells, microorganisms and remnants of food and drink; it is essential to cleanse and refine the saliva samples to remove any external elements. Immediate processing of the sample is recommended in order to avoid decomposition, where this is not possible, the sample may be stored at -80ºC. Salivary analysis – much the same as blood analysis – aims to identify diverse medication or indications of certain diseases while providing a relatively simple tool for both early diagnosis and monitoring various irregularities. The practicalities of salivary analysis have been studied in fields such as: viral and bacterial infections, autoimmune diseases (like Sjögren’s syndrome and cɶliac disease), endocrinopathies (such as Cushing’s syndrome), oncology (early diagnosis of breast, lung and stomach carcinoma and oral squamous cell carcinoma), stress assessment, medication detection and forensic science among others. It is hoped that salivary analysis, with the help of current technological advances, will be valued much more highly in the near future. There still remain contradictory results with respect to analytic markers, which is why further studies into wider-ranging samples are fundamental to prove its viability. Key words:Saliva, biomarkers, early diagnosis.
    Journal of Clinical and Experimental Dentistry 10/2012; 4(4):e237-e243. DOI:10.4317/jced.50865
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    • "Many years after the initial reports of salivary cortisol determination [1] midnight salivary cortisol, along with low dose dexamethasone test (LDDST) and urinary free cortisol (UFC) measurement [2], has become a first-line laboratory method in the diagnosis of Cushing's syndrome (CS). However, there are marked differences between different studies in the sensitivity and specificity of salivary cortisol assays [3] [4] [5] [6] [7], which may be due to not only differences in clinical settings and the composition of control groups, but they may be also related to differences in the diagnostic performance of various laboratory methods [8] and variations in sample collection techniques [4] [11]. Until nowadays, only a few studies reported the diagnostic applicability of an automated electrochemiluminescence immunoassay for the measurement of salivary cortisol [8] [9]. "
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    ABSTRACT: The cut-off value for salivary cortisol measurement for the diagnosis of Cushing's syndrome (CS) may depend both on the severity of the disease and the composition of control group. Therefore, we examined the utility of midnight salivary cortisol measurements in patients who were evaluated for signs and symptoms of CS or because they had adrenal incidentalomas. Because serum osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also investigated whether OC could have a role in the diagnosis of CS. Each of the 151 patients was included into one of the following groups: (A) overt CS (n=23), (B) subclinical CS (n=18), (C) inactive adrenal adenomas (n=40), (D) patients without HPA disturbances (n=70). Patients (C+D) were used as controls. Serum, salivary and urinary cortisol, and OC were measured by electrochemiluminescence immunoassay. Group A had suppressed OC as compared to both group B and group (C+D). Serum and salivary cortisol concentrations showed strong negative correlations with OC in patients with overt CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790 and 0.9940, respectively) serum cortisol after low dose dexamethasone test (0.9930) and OC (0.9220) obtained from ROC analysis for the diagnosis of overt CS were not statistically different. This study confirms the usefulness of midnight salivary cortisol measurements in the diagnosis of overt CS in the everyday endocrinological praxis. Our results suggest that OC may have a role in the diagnosis of overt CS.
    Steroids 01/2011; 76(1-2):38-42. DOI:10.1016/j.steroids.2010.08.007 · 2.64 Impact Factor
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