What are the diagnostic criteria for Cushing disease?

Cushing’s disease, a subset of Cushing’s syndrome, is a condition characterized by an excess of the hormone cortisol in the body. It is most commonly caused by a pituitary tumor leading to an overproduction of adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce cortisol.

The diagnosis of Cushing’s disease is a three-step process:

Clinical Suspicion: The first step in diagnosing Cushing’s disease is suspecting its presence based on the patient’s symptoms and signs. These can include unusual findings for their age such as osteoporosis or hypertension in young adults, multiple progressive features of Cushing’s syndrome such as facial plethora, proximal myopathy, wide (>1 cm) and red/purple striae, and easy bruising. Unexplained severe features like resistant hypertension or osteoporosis at any age can also raise suspicion.

Biochemical Confirmation: Once there is a clinical suspicion of Cushing’s disease, the next step is to confirm the presence of hypercortisolism. This is done through biochemical tests. The Endocrine Society recommends the initial use of one test with high diagnostic accuracy. These tests can include measurements of late-night salivary cortisol, 24-hour urine free cortisol, or low-dose dexamethasone suppression.

Determination of Cause: After confirming the presence of hypercortisolism, the final step is to determine its cause. This involves differentiating between ACTH-dependent and ACTH-independent Cushing’s syndrome, and if it’s ACTH-dependent, further determining whether it’s due to a pituitary or ectopic source.

It’s important to note that the diagnosis of Cushing’s disease can be challenging, especially in mild cases. There is a wide spectrum of clinical manifestations at any given level of hypercortisolism, and the accumulation of new features increases the probability that the syndrome is present.

Because Cushing’s syndrome tends to progress, caregivers are encouraged to consider Cushing’s syndrome as a secondary cause of conditions such as obesity, depression, diabetes, hypertension, or menstrual irregularity, particularly if additional features of the disorder are present. If Cushing’s syndrome is not considered, the diagnosis is often delayed.

In conclusion, diagnosing Cushing’s disease involves a careful evaluation of clinical symptoms, biochemical testing, and determination of the cause of hypercortisolism. It requires a thoughtful and experienced healthcare provider, as the condition can often mimic other common conditions and its symptoms can vary widely among patients.