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  • Review Article
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Late-night salivary cortisol measurement in the diagnosis of Cushing's syndrome

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 344–350 (2008)Cite this article

Abstract

Making a definite diagnosis of Cushing's syndrome is a challenging problem. Unsuspected Cushing's syndrome occurs in 2–3% of patients with poorly controlled diabetes, 0.5–1% with hypertension, 6–9% with incidental adrenal masses, and 11% with unexplained osteoporosis and vertebral fractures. The increasing recognition of this syndrome highlights the need for a simple, sensitive, and specific diagnostic test. Patients with Cushing's syndrome consistently do not reach a normal nadir of cortisol secretion at night. The measurement of late-night salivary cortisol levels might, therefore, provide a new diagnostic approach for this disorder. Salivary cortisol concentrations reflect those of active free cortisol in plasma and saliva samples can easily be obtained in a nonstressful environment (e.g. at home). Late-night salivary cortisol measurement yields excellent overall diagnostic accuracy for Cushing's syndrome, with a sensitivity of 92–100% and a specificity of 93–100%. Several factors can, however, make interpretation of results difficult; these factors include disturbed sleep–wake cycles, contamination of samples (particularly by topical corticosteroids), and illnesses known to cause physiologic activation of the pituitary–adrenal axis. In this Review, we discuss the methods and value of measuring salivary cortisol for the diagnosis of Cushing's syndrome, and put forward some recommendations to maximize accuracy of results.

Key Points

  • Cushing's syndrome is an endocrinopathy with serious complications and high associated mortality

  • The prevalence of Cushing's syndrome is higher than previously appreciated, particularly in high-risk patient populations (e.g. individuals with diabetes, osteoporosis, and incidental adrenal masses)

  • Late-night salivary cortisol testing can identify failure to achieve a normal circadian nadir and may, therefore, be used in the diagnosis of Cushing's syndrome

  • Late-night salivary cortisol has sensitivity of 92–100% and specificity of 93–100% for the diagnosis of Cushing's syndrome

  • Several factors should be kept in mind when interpreting late-night salivary cortisol results (e.g. abnormal sleep–wake cycle, acute stress, and contamination with topical steroids)

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Figure 1: Algorithm for the diagnosis of Cushing's syndrome.

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Authors and Affiliations

  1. T Carroll is a Clinical Fellow and H Raff and JW Findling are Professors in the Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, and H Raff is Director of the Endocrine Research Laboratory and JW Findling is Director of the Endocrine-Diabetes Center in the Aurora St Luke's Medical Center, Milwaukee, WI, USA.,

    Ty Carroll, Hershel Raff & James W Findling

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Correspondence to Hershel Raff.

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Competing interests

JW Findling acts as a consultant to Corcept Therapeutics.

The other authors declared no competing interests.

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Carroll, T., Raff, H. & Findling, J. Late-night salivary cortisol measurement in the diagnosis of Cushing's syndrome. Nat Rev Endocrinol 4, 344–350 (2008). https://doi.org/10.1038/ncpendmet0837

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