Approach to patients with pseudo-Cushing’s states
The distinction between pseudo-Cushing’s states (PCS) and Cushing’s syndrome (CS) poses a significant clinical challenge even for expert endocrinologists. Appropriate treatment of underlying conditions is essential as it can reverse the hormonal abnormalities associated with PCS. Close surveillance and a thorough assessment of a patient’s hormone status will ultimately orient the diagnosis and treatment options over time.

Clinical situations involving HPA axis activation giving rise to a so-called PCS remain a major diagnostic challenge for endocrinologists.

Patients may present with obesity, DM, depression, and PCOS that are frequent in the general population. At diagnosis, the patients will often have already consulted several specialists (gynecologists, psychiatrists, and internists) and may have been given different treatments that could interfere with their laboratory test results or confer an additional risk for patients with an occult CS.

An accurate clinical examination is needed to identify any features that might help to discriminate cases of CS, but such signs might not be apparent in mild hypercortisolism, making its diagnosis more difficult.

An accurate treatment of any condition that may lead to a suspected PCS is important because it can reverse the related hormone abnormalities. We encourage physicians to consider CS particularly if the patient has more than one feature of the disorder or a poor control of the single situation despite maximal therapy.

The choice of the optimal screening test in a high-risk population relies on an expert understanding of the diagnostic performance of the various tests in different clinical settings. Although LC–MS/MS is probably the most accurate method for assessing UFC levels, have not achieved widespread use in routine clinical practice, and steroid cross-reactivity remains an issue when immunoassays are used to measure serum and urinary cortisol levels. LNSC needs to be further validated for use in this setting, demonstrating its accuracy in the differential diagnosis of PCS and CS.

Regarding the Dex–CRH test and/or the easier and less expensive DDAVP test, there is still debate on the optimal cut-off values for each of these tests in different clinical settings (obesity, MDD, and alcoholism), and none of them has become the gold standard for differentiating CS from PCS.

When a diagnosis is unreliable, we suggest treating the associated conditions and adopting a close follow-up, because the hypercortisolism associated with CS may progress, and the condition might consequently be diagnosed at a later date.