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Pseudo-Cushing Syndrome

Overview

Pseudo- Cushings syndrome (PCS) is a group of conditions associated with clinical and biochemical features of Cushing syndrome, but the hypercortisolemia is usually secondary to other factors.
 It is very important to rule out these conditions before making a diagnosis of Cushings syndrome, as it may subject the patient to unnecessary investigations and possible harmful interventions. Some frequently occurring illnesses can induce a phenotype that largely overlaps with Cushing syndrome and is accompanied by hypercortisolism.

These illnesses include the following:

Depression

Obesity

Physical stress

Malnutrition

Eating disorders

Polycystic ovarian syndrome (PCOS)

Uncontrolled diabetes

Obstructive sleep apnea (OSA)

Chronic alcoholism

 A particular type of hypercortisolism presenting during the above conditions, named functional hypercortisolism, is caused by chronic activation of hypothalamic-pituitary-adrenal (HPA) axis. It is usually mild and disappears when the underlying disorder is resolved.

PCS initially was described by Smalls et al, in 1976; the investigators reported 3 cases of alcoholic patients who had the physical and biochemical abnormalities of Cushing syndrome.
Most of the abnormalities disappeared after 1-3 weeks of alcohol abstinence. Similar abnormalities have also been described in patients with severe endogenous depression.
Abnormal cortisol secretion usually disappears after remission of depression.

Epidemiology

In a study of 56 men in an alcohol detoxification unit, 18% had nonsuppressible serum cortisol levels. Many of these patients lacked the physical stigmata of Cushing syndrome, and some biochemical abnormalities resolved in a few days.
Hypercortisolemia is evident in approximately 50% of depressed patients and is particularly characteristic in the melancholic subtype.
In a study of 190 patients with type 2 diabetes, 63 subjects (33%) had high cortisol concentrations.

PCS can occur at any age; it can develop in infants exposed to alcohol in breast milk.

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