Clinical decision making for patients with suspect
hypercortisolism involves a complex diagnostic assessment.
Cushing's syndrome remains one of the most challenging endocrine pathologies. Most clinical features overlap with those of common diseases found in the general population, and some patients have an atypical clinical presentation with only isolated symptoms. Recently, several studies have suggested that the prevalence of
Cushing's syndrome is higher than previously thought. Therefore, efficient screening tests are needed to identify the few uncovered patients also among unselected high-risk ambulatory patients with disorders potentially related to
cortisol excess. The recommended diagnostic tests are 24-h urinary free
cortisol, 1-mg overnight
dexamethasone suppression test, and late-night salivary
cortisol. Once the diagnosis of
Cushing's syndrome is established, the next step is the measurement of plasma
ACTH. Then, dynamic test and appropriate imaging procedures are the most useful noninvasive investigations for the differential diagnosis. Patients with
Cushing's disease are generally responsive to the CRH test and to high-dose
glucocorticoid feedback. Bilateral inferior petrosal sinus sampling is considered the gold standard for establishing the origin of
ACTH secretion, and it is recommended in patients with
ACTH-dependent
Cushing's syndrome whose clinical, biochemical, or radiological studies are discordant or equivocal. The present clinical case shows that even if rare, the ectopic
ACTH secretion should be considered also in those cases where the pretest probability is low. The management of
Cushing's syndrome depends on the exact knowledge of its various causes, paying attention to the many potential diagnostic pitfalls. The choice of test, the modality of specimen collection (blood, urine, and saliva), the quality of measurement (assay methodology and standardization), and close dialogue among endocrinologists, chemical pathologists, and neuroradiologists are key factors for optimal care of patients.