Diagnostic Testing For Cushing’s Syndrome

A screening evaluation for the possibility of Cushing’s syndrome should be considered in any patient with signs and symptoms of excessive cortisol secretion. Abnormal weight gain, particularly in the central location accompanied by hypertension, diabetes, or hyperlipidemia should always signal the possibility of Cushing’s syndrome. Many patients with this disorder will also have facial rounding with the so-called “moon faces.” Accumulation of fat above the clavicles or behind the neck are also common features of excessive cortisol secretion. Some patients will also present with osteoporosis (particularly rib fractures) and some have muscle weakness. The presence of wide purplish striae (stretch marks) in the abdomen or elsewhere can also be a symptom of Cushing’s syndrome. The majority of patients with Cushing’s syndrome have some type of neuropsychiatric problem (particularly depression) or even some cognitive impairment. Fatigue is almost always present in patients with Cushing’s. In addition, women with the polycystic ovary syndrome should also all be screened for the possibility of Cushing’s syndrome. The most appropriate diagnostic approach to patients with suspected Cushing’s syndrome is somewhat controversial; however, four diagnostic studies are currently used: late-night salivary cortisol, 24 hour urine free cortisol, lowdose dexamethasone suppression, and the dexamethasoneCRH test. Three tests are summarized in Figure 1. Late-Night Salivary Cortisol Late-night salivary cortisol is emerging as the most sensitive diagnostic test for Cushing’s syndrome. Elevated cortisol between 11:00 p.m. and midnight appears to be the earliest detectable abnormality in patients with this disorder. Cortisol secretion is usually very low at this time of the day, but in patients with Cushing’s syndrome, the value is virtually always elevated. Although this is a relatively new test, it is currently the most widely studied single test for the diagnosis of Cushing’s syndrome with at least eight independent studies from all over the world demonstrating sensitivity of 93-100% for the diagnosis of Cushing’s syndrome. In the United States, there is only one FDA-approved assay for the measurement of salivary cortisol in the diagnosis of Cushing’s syndrome. Collection of saliva requires special sampling tubes; however, this is a very easy test for patients to perform and can be done on multiple occasions. Salivary cortisol is very stable at room temperature and the samples can actually be mailed to a reference laboratory. Normal levels of late-night salivary cortisol virtually exclude the diagnosis of Cushing’s syndrome. Urine Free Cortisol 24 hour urine free cortisol has, until recently, been considered the gold standard for the diagnosis of cortisol excess. A 24 hour urine free cortisol level does reflect the cortisol secretion throughout an entire day. Although the majority of