The Role of the Laboratory in the Diagnosis of Cushing's Syndrome

Cushing's syndrome remains one of the most difficult diagnostic problems in endocrinology. Patients with suspected ACTH-dependent Cushing's syndrome continue to challenge the diagnostic skills of the clinical scientist and clinician, even with the array of biochemical tests and imaging techniques now available. The diagnosis of Cushing's syndrome rests on demonstrating over-production of cortisol and relative resistance of this over-production to biochemical manipulation. However, there are causes of hypercortisolism other than Cushing's syndrome: these and the types of Cushing's syndrome have been summarized in Table I. Clinical suspicion of endogenous hypercortisoIism can only be confirmed biochemically. To initiate the most appropriate and effective treatment it is essential, even in the most overt cases of Cushing's syndrome, to identify the primary abnormality causing the hypercortisolism. In many cases, the initial tests can be conducted on an out-patient basis, but confirmation will usually require in-patient assessment. Differential diagnosis is often possible only under strictly controlled in-patient provocative testing. Biochemical tests for the existence and differential diagnosis of Cushing's syndrome have been extensively reviewed1-8 and consist of a variety of first-line and definitive tests. Commonly used first-line tests include the overnight low-dose dexamethasone suppression test (LDDST) and measurement of the 24 h urinary excretion of free cortisol (UFC). Although these tests are far from infallible, negative results markedly decrease the likelihood