Issues in the diagnosis of Cushing's syndrome for the primary care physician

The diagnosis of Cushing's syndrome is one of the most difficult and yet one of the most important ones a primary care physician can make. The clinical presentation overlaps that of many other common diseases, but more specific signs such as unexplained osteoporosis, muscle weakness, ecchymoses, hypokalemia, and central obesity, the presence of multiple symptoms affecting different body systems, and a demonstrated change over time should prompt the screening evaluation. We recommend a step-wise approach to the diagnostic evaluation. Step 1 involves demonstrating pathologic hypercortisolemia and thus making the diagnosis of Cushing's syndrome. In step 2, distinguishing ACTH-independent disease from ACTH-dependent disease and then adrenal imaging is done. Finally, for patients with ACTH-dependent disease, step 3 entails anatomic localization of the ACTH source by MRI, if unequivocal, or by IPSS or CSS. Only when the evaluation is done in a step-wise fashion can the clinician be assured that appropriate treatment recommendations can be made. Although a fair amount of the testing is complex, requiring special facilities and usually the assistance of an endocrinologist, the most critical step is that done by the primary care physician--considering the diagnosis and initiating the screening algorithm.