Diagnosing Cushing's Disease

Cushing's disease is a rare endocrine disorder characterized by the overproduction of the hormone cortisol, typically caused by a benign tumor in the pituitary gland known as an adenoma.

This excessive cortisol secretion leads to a range of physical and emotional symptoms, including weight gain, muscle weakness, and even high blood pressure. These symptoms can significantly impact an individual's quality of life and overall health.

Diagnosis involves a combination of clinical evaluation, laboratory tests, and imaging studies, followed by treatment options such as surgery, medication, or radiation therapy, aimed at normalizing cortisol levels and alleviating symptoms.

Cushing’s disease can affect individuals of various ages and backgrounds, but certain factors may increase the risk of developing this condition; for example, individuals commonly between 20 and 50 years old are diagnosed and almost three times as many women are affected versus men.

In this article, we will delve into the various aspects of diagnosing Cushing's disease. By examining each diagnostic step in detail, we aim to provide a comprehensive understanding of how healthcare professionals pinpoint the presence of Cushing's disease and distinguish it from other related conditions.

Initially, the diagnosis relies on an evaluation of the patient's medical history, physical examination, and results from laboratory tests. Heightened cortisol levels will prompt additional confirmatory tests.

Diagnosing Cushing's disease can present challenges due to the daily cortisol level fluctuations and the often very small size of tumors (microadenomas). The primary objective of diagnostic testing is to corroborate the presence of an ACTH-producing pituitary adenoma, while simultaneously excluding other potential sources of excessive cortisol production, as detailed by the following tests.

• 24-hour urinary excretion of cortisol test: This test involves collecting all urine produced over a 24-hour period, which is then analyzed to measure the level of cortisol present. Elevated cortisol levels in the urine can indicate the presence of Cushing's disease.
• Late-night salivary cortisol test: Cortisol levels naturally reach their lowest point during the nighttime. In this test, cortisol levels are assessed using saliva samples collected close to midnight. A negative result from this test strongly indicates the absence of Cushing’s syndrome.
• Low-dose dexamethasone suppression test: This test checks how well the pituitary gland controls hormone levels. You take a medicine called dexamethasone, which is similar to cortisol, to lower ACTH and cortisol levels. The next day, your blood or urine is tested to see if cortisol levels have dropped. If they don’t go down as expected, it may suggest Cushing’s syndrome. More tests are needed to find out why too much cortisol is being made.
• High-dose dexamethasone suppression test: This test is used when the low-dose dexamethasone suppression test gives abnormal results. Its goal is to find out whether a pituitary adenoma or another type of tumor is causing high cortisol levels. A higher dose of dexamethasone is given. If cortisol levels drop, it suggests a pituitary adenoma (Cushing’s disease). If cortisol levels stay high, it suggests a tumor in the adrenal glands or another area is causing the problem.
• Pituitary Magnetic Resonance Imaging (MRI): Magnetic resonance imaging stands as the most preferred approach for visualizing brain structures and the pituitary gland. Once external factors like medications are ruled out as a cause for elevated cortisol levels, the next step involves conducting MRI of the brain. This MRI scan aims to detect the presence of a pituitary adenoma.
• Inferior Petrosal Sinus Sampling (IPSS): Inferior Petrosal Sinus Sampling (IPSS) is a special test that helps find the source of high ACTH levels. A catheter is inserted through blood vessels to take samples from veins near the pituitary gland and from a vein in another part of the body. By comparing ACTH levels in these samples, doctors can tell if the pituitary gland is making too much ACTH.

While Cushing's syndrome refers to elevated cortisol levels originating from any source, Cushing's disease specifically refers to elevated cortisol levels caused by a pituitary tumor (pituitary adenoma). Prolonged usage of corticosteroid medications like prednisone, hydrocortisone, and dexamethasone is the most frequent cause for Cushing's syndrome.

Diagnosing Cushing's syndrome involves identifying the presence of elevated cortisol levels, which can result from various causes such as adrenal tumors, medications, or other health conditions. In contrast, diagnosing Cushing's disease specifically looks for a pituitary adenoma, which can be confirmed through an MRI.

Several medical conditions can be mistaken for Cushing's syndrome due to overlapping symptoms. These include obesity, metabolic syndrome, polycystic ovary syndrome (PCOS), depression, and certain forms of thyroid dysfunction.

The dexamethasone suppression test, specifically the high-dose dexamethasone suppression test, is often used to differentiate between Cushing's syndrome and Cushing's disease. This test helps to determine whether the cause of elevated cortisol levels is due to an ACTH-producing pituitary adenoma (Cushing's disease) or other sources (Cushing's syndrome).

If cortisol levels significantly lower (suppress) with high-dose dexamethasone, it suggests a pituitary origin (Cushing's disease), while lack of suppression points to other causes of Cushing's syndrome.

• Three signs of Cushing's disease are weight gain, facial changes, and easy bruising.
• A combination of urinary, salivary, and blood tests may be used to assist in diagnosis.
• Elevated cortisol levels stem from various sources in Cushing's syndrome, whereas the cause is a pituitary tumor in Cushing's disease.

• Endocrine Society
• Pituitary Foundation
• Urology Care Foundation
• National Adrenal Diseases Foundation