Back to Basics—When Should Cushing Syndrome Be Suspected?

Abstract

Evaluation of patents suspected to have Cushing syndrome is one of the most challenging tasks encountered by the endocrinologist. Many of the symptoms and signs that patients with Cushing syndrome frequently experience, including fatigue, weight gain, and hypertension, are also common in the general population, and are therefore of little help during the diagnostic workup. The probability of diagnosing Cushing syndrome in, for example, patients with obesity and metabolic syndrome is about 1 in 500 (1). Similarly, the biochemical analyses used to screen for hypercortisolism—late-night salivary cortisol, urinary free cortisol, and the dexamethasone suppression test—all come with limitations where false-positive and false-negative test results are common. In fact, the sensitivity and specificity of all these tests are “only” approximately 90% (2). Even using of 2 or more of these tests in combination does not achieve better diagnostic accuracy (3). This, and the fact that the clinical features are frequently unspecific, is unfortunate and explains the long diagnostic delay that is common among patients with Cushing syndrome (4).