Question: Is testing for Cushing's more difficult and can some tests come back normal when you haven't had Cushing's very long?

Answer: As with most conditions, if the diagnosis is obvious clinically, then biochemical confirmation is usually simple; if the diagnosis is not clear, then biochemical confirmation or exclusion of the diagnosis is often much more difficult. This is especially true for Cushing's syndrome and several attempts over a period of weeks or months may be necessary to establish or exclude the diagnosis in particularly difficult cases. Even then, the possibility of error will remain. This is especially early in the disease process or in mild cases. One reason for the problem has to do with how normal ranges are calculated. Frequently, that normal range is developed by using a reference group of people assumed (or shown) to be disease-free. Ideally, when using a test to exclude the diagnosis of Cushing's syndrome, the reference group should be made up of individuals who look like they have the disease, but do not. However, reference groups are usually made up of individuals who are readily accessible (medical students, lab technicians, etc.) and not more appropriate comparisons. Another reason has to do with the levels chosen to indicate disease. This level is usually a compromise between detecting everyone who has the disease and avoiding falsely identifying disease-free individuals as having the disease.