CushieBlog

Caused by excessive exposure to the hormone cortisol, endogenous Cushing syndrome (CS) is difficult to diagnose. Currently available biochemical tests that assess cortisol production have limited diagnostic specificity and sensitivity, and their performance can vary depending on the patient, according to a review article in Current Opinion in Endocrinology, Diabetes and Obesity.

“Whether performed on blood, urine, saliva, or hair, all biochemical tests for CS have advantages and disadvantages. It is therefore essential to select them based on the individual characteristics of the patient and the stage of the disease in order to improve their diagnostic performance,” wrote corresponding author Antoine Tabarin, MD, and coauthor Amandine Ferriere, MD, of the University Hospital of Bordeaux in Pessac, France.

The Endocrine Society recommends initial screening of patients with suspected CS using 24-hour urinary-free cortisol (UFC), late-night salivary cortisol (LNSC), or the overnight dexamethasone suppression test (ONDST). To avoid false negatives from variability in cortisol production, UFC and LNSC tests should be performed twice.

Among the three screening options, meta-analysis findings suggest comparable diagnostic performance, the authors reported.

“However, they also concluded that these investigations should not be used indiscriminately,” the review continued, “and should be selected according to various circumstances.”

ONDST results can be affected by medications, age, a history of bariatric surgery, and even individual differences in dexamethasone metabolism, according to the review. UFC requires patient education and a complete 24-hour urine collection. LNSC testing, which biochemically assesses the loss of circadian rhythmicity consistent in CS, may not be appropriate for people with highly variable sleep schedules, including shift workers.

For early detection of Cushing disease (CD) recurrence after pituitary surgery, LNSC is the recommended first-line procedure for biochemical follow-up. LNSC is also the tool of choice for monitoring patients with CS treated with medication, the article reported.

For patients with adrenocorticotropic hormone (ACTH)-dependent CS, UFC offers high accuracy for assessing the likelihood of CD and ectopic adrenocorticotropin. However, for the diagnosis of cyclical or intermittent CS, repeat UFC tests are “cumbersome and nearly impossible,” the authors wrote.

LNSC, on the other hand, allows for frequent daily assessment of cortisol secretion which is helpful for identifying cyclical CS. Similarly, measurements of cortisol and cortisone levels in the hair can assess mid- to long-term tissular exposure to cortisol and signal cyclical CS as well, the review explained.