Cushing's Syndrome: Where and How to Find It

The diagnosis of Cushing's syndrome is challenging to endocrinologists as patients often present with an insidious history, together with subtle external clinical features. Moreover, complications of endogenous hypercortisolism, such as visceral obesity, diabetes, hypertension and osteoporosis, are conditions commonly found in the population, and discerning whether these are truly a consequence of hypercortisolism is not straightforward. To avoid misdiagnosis, a careful investigative approach is essential. The investigation of Cushing's syndrome is a three-step process. Firstly, after exclusion of exogenous glucocorticoid use, the decision to initiate investigations should be based on whether there is a clinical index of suspicion of the disease. Specific signs of endogenous hypercortisolism raise the a priori probability of a truly positive test. Secondly, if the probability of hypercortisolism is high, one should carry out specific tests as indicated by Endocrine Society guidelines. Populations with non-distinguishing features of Cushing's syndrome should not be screened routinely as biochemical tests have a high false-positive rate if used indiscriminately. Thirdly, once hypercortisolism is confirmed, one should move to establish the cause. This usually entails distinguishing between adrenal or pituitary-related causes and the remoter possibility of the ectopic adrenocorticotropic hormone syndrome. It is crucial that the presence of Cushing's syndrome is established before any attempt at differential diagnosis.