To assess the likelihood of Cushing's syndrome, a structured approach based on specific diagnostic criteria is employed. This involves evaluating several key factors to understand the presence of hypercortisolism, the hallmark of Cushing's syndrome.

The initial step is to exclude any physiological causes of excess cortisol or exogenous corticosteroid exposure. This is a critical first criterion and serves as a prerequisite for further testing.

Following this, the user considers additional biochemical tests:

- **24-hour urinary free cortisol**: This test measures the amount of cortisol in the urine over a day. For Cushing’s syndrome to be considered likely, results should show cortisol levels above the normal upper limit on at least two separate measurements.

- **Late-night salivary cortisol**: Normally, cortisol levels are low at night. For this criterion, a reading of greater than 145 ng/dL (or > 4 nmol/L) on two or more occasions suggests a disruption in the typical diurnal pattern of cortisol production.

- **Serum cortisol after dexamethasone administration**: Dexamethasone is a synthetic steroid used to suppress cortisol production. If, after receiving a 1 mg dose overnight, the serum cortisol level remains greater than 1.8 mcg/dL (or > 50 nmol/L), it indicates a potential problem with cortisol regulation.

The conclusion about the likelihood of Cushing's syndrome is made by integrating these factors:

- The syndrome is likely if there is proven exclusion of other causes (the first criterion) and at least two of the following are satisfied: elevated 24-hour urinary free cortisol, elevated late-night salivary cortisol, or failure to suppress serum cortisol after dexamethasone.

- If this combination of exclusion and elevation criteria is not met, Cushing's syndrome is considered unlikely.

This diagnostic pathway allows for a comprehensive yet straightforward determination, focusing on biochemical validations and excluding other possible explanations before arriving at a clinical interpretation.

The diagnostic criteria for Cushing's syndrome is a clinical tool designed to aid in the identification and diagnosis of Cushing's syndrome, a condition characterized by excessive cortisol production. This tool is particularly useful in distinguishing Cushing's syndrome from other conditions with similar symptoms and from physiological causes of hypercortisolism, as well as exogenous corticosteroid exposure.

The primary components of this diagnostic criteria include the exclusion of physiological causes of hypercortisolism and exogenous corticosteroid exposure, and the presence of certain biochemical abnormalities. These abnormalities include 24-hour urinary free cortisol levels above the upper limit of normal on two or more separate measurements, late-night salivary cortisol levels greater than 145 ng/dL on two or more separate measurements, and serum cortisol levels greater than 1.8 mcg/dL after 1 mg overnight dexamethasone.

The diagnosis of Cushing's syndrome is considered likely if the patient meets the exclusion criteria and has either elevated urinary and salivary cortisol levels, elevated urinary cortisol and serum cortisol levels after dexamethasone, or elevated salivary cortisol and serum cortisol levels after dexamethasone. If these criteria are not met, a diagnosis of Cushing's syndrome is considered unlikely. This diagnostic tool thus provides a structured approach to the diagnosis of Cushing's syndrome, facilitating early detection and treatment of this condition.

Diagnostic criteria for Cushing's syndrome