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In a recent of Cushing's syndrome, Donald Lynn Loriaux, MD, of Oregon Health & Science University, tackles a common and challenging clinical dilemma: Now that roughly one-third of Americans are obese, how can we accurately distinguish the rare patient with Cushing's syndrome from the many patients with common metabolic complications of obesity?
Loriaux estimates that the probability that a patient with metabolic syndrome has Cushing's syndrome is roughly 1 in 500. How do we identify those rare patients who require timely diagnosis of abnormal glucocorticoid excretion while avoiding unnecessary diagnostic studies (and attendant false positive results)?
A meticulous physical exam -- particularly the skin exam -- can help distinguish Cushing's syndrome from the much more common obesity-related metabolic complications. Cortisol-induced changes include thin skin and ecchymoses, which are not typical complications of obesity.
Skinfold thickness can be measured over the middle finger of the non-dominant hand using calipers and a millimeter ruler, and thin skin (<2 mm) increases the likelihood ratio of Cushing's syndrome by 116. If the patient has ecchymoses, the likelihood ratio is 4, and osteopenia, 18 -- two other consequences of Cushing's but not obesity. (Ecchymoses are not likely to be useful by themselves as the odds would increase from 1 in 500 to only 4 in 500, but would be helpful combined with other typical findings.)
Violaceous stria are another helpful finding. Loriaux explained to us in a separate email that clinicians may be able to see "through the skin to the muscle below. Other criteria are [stria] greater than 1 cm in width, and crossing 'Langer's lines' of stress in the abdominal skin, rather than following the lines of stress. In [Cushing's syndrome], the dermis is ruptured due to weak skin, rather than [typical stria which are] due to the magnitude of the stress, usually an expanding uterus."
For patients with the metabolic syndrome combined with thin skin or violaceous stria, the next step is measuring 24-hour urine-free cortisol and creatinine. Levels of urine free cortisol >60 micrograms per 24 hours, combined with key clinical findings, should lead directly to determining the source of the excess cortisol. This should be followed by measuring serum corticotropin and pursuing additional diagnostic studies based on the results.
Notably, the dexamethasone suppression test, a traditional diagnostic evaluation for Cushing's, is no longer recommended. The author notes that dexamethasone-suppression tests are no longer believed to be useful diagnostically in the setting of the obesity epidemic; he calculates the positive predictive value to be only 0.4%.
This superb review is not only a modern guide to detecting the unusual case of Cushing's syndrome but also a model of applying Slow Medicine to diagnostic dilemmas. Instead of relying on screening of many patients with diagnostic studies that will lead to more false positives than true positives, a seasoned clinician shares with us how we can use a meticulous physical exam to identify the rare patient in need of additional evaluation.
"Updates in Slow Medicine" applies the latest medical research to support a thoughtful approach to clinical care. It is produced by , of Harvard Medical School, and , of the Keck School of Medicine at the University of Southern California. To learn more, .