Supraphysiological exposure to glucocorticoids causes Cushing’s syndrome, which is linked to considerable morbidity and death. The pathophysiology involves either autonomous cortisol overproduction, whether or not it is adrenocorticotropin hormone (ACTH) dependent (endogenous Cushing’s syndrome), or the use of corticosteroids (exogenous Cushing’s syndrome).

Although a prompt diagnosis of Cushing’s syndrome is recommended, it can be difficult to make in clinical settings (leading to pseudo-syndrome). Therefore, Cushing’s Starting the first workup by eliminating local and systemic corticosteroid usage is recommended. First-line screening procedures such as the 1-mg dexamethasone suppression test, 24-hour urine-free cortisol excretion, and late-night salivary cortisol measurement should be carried out to check for endogenous Cushing’s syndrome.

The evaluation of long-term glucocorticoid exposure and the diagnosis of brief episodes of hypercortisolism, such as those seen in cyclical Cushing’s syndrome, were aided by scalp-hair cortisol/cortisone analysis. Due to the unique patient features, it might be challenging to interpret the results; thus, it’s essential to be aware of the limits of the test. Measurement of plasma ACTH concentrations distinguished between ACTH-dependent causes (80-85%) or ACTH-independent (15-20%) once endogenous Cushing’s syndrome has been identified.

Finding the exact etiology of Cushing’s syndrome required further evaluation using several imaging modalities and dynamic biochemical tests, including bilateral inferior petrosal sinus sampling. The diagnostic workup of Cushing’s syndrome is covered in this issue of “Approach to the Patient” by addressing the issues of when to screen, how to screen, and how to distinguish between the many causes. Recent advancements in biochemical and imaging methods are also explored in this regard.