How Is Cushing’s Syndrome Diagnosed?

Cushing’s syndrome is an important hormonal disorder that occurs as a result of having higher-than-normal levels of cortisol in the body for a prolonged period. Cortisol is one of the essential hormones that affects the stress response, blood sugar, blood pressure, the immune system, and metabolism. However, when cortisol levels remain elevated for a long time, they can cause weight gain, muscle weakness, skin changes, high blood pressure, elevated blood sugar, and various hormonal problems.

A Cushing’s diagnosis is not made solely by looking at the patient’s physical appearance or symptoms. During the diagnostic process, the first step is to determine whether excess cortisol is actually present. Then, the source of excessive cortisol production is investigated. Hormone tests, blood and urine analyses, saliva tests, and, when necessary, imaging methods are used during this process.

Prof. Dr. Ömür Günaldı emphasizes the importance of carrying out the diagnostic process carefully and step by step in the clinical evaluation of patients with suspected Cushing’s syndrome. In particular, since Cushing’s disease may originate from the pituitary gland, hormone test results should be evaluated together with the patient’s clinical findings.

Why Is Cushing’s Syndrome Difficult to Diagnose?

Diagnosing Cushing’s syndrome may not be easy in some patients. The main reason for this is that the symptoms of the disease can also occur in many other health conditions.

For example, weight gain, fatigue, high blood pressure, elevated blood sugar, depressed mood, or menstrual irregularities are not specific to Cushing’s syndrome alone. Therefore, the doctor evaluates when the patient’s symptoms began, how long they have persisted, and how they have changed over time.

In particular, the presence of the following symptoms together may require further investigation for Cushing’s syndrome:

• Significant weight gain in the trunk and abdominal area
• Rounding of the face
• Fat accumulation in the neck and upper back
• Wide purple or red stretch marks on the skin
• Easy bruising
• Thinning of the skin
• Muscle weakness
• High blood pressure
• Elevated blood sugar
• Menstrual irregularities
• Excessive hair growth
• Psychological changes

The First Step in Cushing’s Diagnosis: Patient Evaluation

In the first stage of the diagnostic process, a detailed medical history is taken and a physical examination is performed. The doctor carefully evaluates the medications the patient is using.

This is because one of the important causes of Cushing’s syndrome is the long-term or high-dose use of corticosteroid medications used for treatment purposes. These medications may be taken orally, but in some cases they may also be used through injections, inhalers, creams, or other routes of administration.

Therefore, it is important for the patient to inform the doctor about all medications being used. It is also not appropriate to suddenly stop medications containing cortisone without a doctor’s recommendation.

Prof. Dr. Ömür Günaldı emphasizes the importance of a multidisciplinary approach in evaluating patients with suspected Cushing’s syndrome, focusing on the patient’s overall clinical picture rather than concentrating on a single symptom.

Cortisol Tests in the Diagnosis of Cushing’s Syndrome

The main objective in diagnosing Cushing’s syndrome is to determine whether the body is producing more cortisol than normal. Different biochemical tests may be used for this purpose.

In the Endocrine Society’s diagnostic approach, certain highly sensitive cortisol tests are recommended for the initial evaluation of appropriate patients. These include late-night salivary cortisol, 24-hour urinary free cortisol, and the low-dose dexamethasone suppression test.

Not every patient needs to undergo all of these tests at the same time. The doctor determines which test should be used according to the patient’s clinical characteristics.

24-Hour Urinary Free Cortisol Test

One of the methods used in the diagnosis of Cushing’s syndrome is measuring the amount of free cortisol in urine collected over a 24-hour period.

Under normal conditions, cortisol production varies throughout the day. In Cushing’s syndrome, however, the regulation of cortisol production may be disrupted, and daily cortisol excretion may be higher than normal.

For the test to provide accurate results, it is important that urine is collected correctly over the entire 24-hour period. Incomplete collection or incorrect procedures during the collection process may affect the test results.

In some patients, the doctor may request more than one 24-hour urine test. The purpose of this is to increase the reliability of the measurement.

Late-Night Salivary Cortisol Test

Cortisol levels do not remain the same throughout the day. In healthy individuals, cortisol levels are generally higher in the morning and lower at night.

In Cushing’s syndrome, this daily rhythm may be disrupted. Finding cortisol levels higher than they should be at night may be an important finding for diagnosis.

For this reason, measuring the cortisol level in a saliva sample collected late at night may be used in the diagnostic process. Because the test is easy to perform, it may be preferred in some patients.

However, it is not appropriate to evaluate the test result on its own. The doctor considers the result together with the patient’s other hormone tests and clinical findings.

What Is the Dexamethasone Suppression Test?

One of the important methods used in the diagnosis of Cushing’s syndrome is the low-dose dexamethasone suppression test.

Dexamethasone is a synthetic glucocorticoid that has effects similar to cortisol. In healthy individuals, when dexamethasone is administered, the body’s own cortisol production is expected to be suppressed.

In some individuals with Cushing’s syndrome, however, this suppression does not occur normally, and cortisol levels may remain elevated.

The way the test is performed and the interpretation of the results should be managed by a doctor. Since medications, certain diseases, and various clinical conditions can affect the test results, it is not appropriate to interpret the results without specialist evaluation.

What Happens After a Cushing’s Diagnosis Is Confirmed?

If the initial tests suggest excess cortisol, the next step is to investigate the source of the condition. This is because Cushing’s syndrome may have different causes.

These may include:

• Excessive ACTH secretion from the pituitary gland
• Excessive cortisol production by the adrenal gland
• The presence of ACTH-producing tumors in other parts of the body
• Long-term use of corticosteroid medications

The condition that develops as a result of excessive ACTH production by the pituitary gland is called Cushing’s disease. Therefore, Cushing’s disease is a specific cause of Cushing’s syndrome.

Why Is the ACTH Test Important in the Diagnosis of Cushing’s Syndrome?

After excess cortisol has been confirmed, the doctor may evaluate the level of the ACTH hormone. ACTH is a hormone secreted by the pituitary gland that stimulates the adrenal glands to produce cortisol.

Based on the ACTH result, the doctor may gain information about the source of excess cortisol.

Low ACTH levels may suggest conditions in which the adrenal gland directly produces excessive cortisol. Normal or high ACTH levels, on the other hand, may raise the possibility of ACTH-dependent Cushing’s syndrome.

This evaluation is not made by looking at a single laboratory value alone. Hormone test results need to be assessed together.

MRI and Other Imaging Methods in Cushing’s Diagnosis

After hormone tests provide information about the source of the disease, the doctor may use imaging methods if considered necessary.

When pituitary-related Cushing’s disease is suspected, pituitary magnetic resonance imaging, or MRI, may be used. MRI can be used to investigate lesions in the pituitary gland that may be associated with hormone production.

If a problem originating from the adrenal gland is suspected, imaging methods such as computed tomography or MRI may be used.

However, there is an important point: Not every pituitary or adrenal gland lesion detected during imaging is necessarily the cause of Cushing’s syndrome. Therefore, imaging results must always be evaluated together with hormone test results and clinical findings.

Are Cushing’s Disease and Cushing’s Syndrome the Same?

Although Cushing’s syndrome and Cushing’s disease are closely related concepts, they are not the same.

Cushing’s syndrome refers to the general condition in which the body is exposed to excessive cortisol for a prolonged period.

Cushing’s disease, on the other hand, is a specific type of Cushing’s syndrome in which excessive ACTH secretion from the pituitary gland causes the adrenal glands to produce excessive amounts of cortisol.

Why Is Early Evaluation Important in Cushing’s Diagnosis?

Prolonged high cortisol levels can affect many systems in the body. Untreated Cushing’s syndrome may lead to complications such as high blood pressure, blood sugar disorders, bone loss, muscle weakness, and cardiovascular problems.

Therefore, it is important to pay attention when several symptoms that may appear unrelated develop in the same person over time.

Prof. Dr. Ömür Günaldı emphasizes an approach in which reaching an accurate diagnosis in patients with suspected Cushing’s syndrome depends not on a single test result, but on the combined evaluation of clinical findings, hormone analyses, and imaging results when necessary.

How Is Treatment Planned After Cushing’s Syndrome Is Diagnosed?

Once the diagnosis has been confirmed, the cause of the condition must first be identified in order to determine the appropriate treatment. In pituitary-related Cushing’s disease, surgical treatment may be one of the primary options for suitable patients.

A surgical approach may be considered for tumors originating from the adrenal gland. In some patients, medications that reduce cortisol production may also be used. The choice of treatment varies according to the cause of the disease, the patient’s overall health condition, and existing complications.

During the treatment process, it is important not only to control cortisol levels but also to monitor blood pressure, blood sugar, bone health, and other problems caused by elevated cortisol.

A Cushing’s diagnosis is a step-by-step process that begins with a detailed clinical evaluation and appropriate hormone tests. The first objective is to determine whether excess cortisol is actually present in the body. Methods such as 24-hour urinary free cortisol, late-night salivary cortisol, and the dexamethasone suppression test may be used for this purpose.

Once excess cortisol has been confirmed, ACTH measurement and, when necessary, imaging of the pituitary or adrenal glands are used to investigate the source of the condition.

Because the symptoms of Cushing’s syndrome may be confused with those of other diseases, self-diagnosis is not appropriate. Specialist evaluation is particularly important when symptoms such as rapid and unexplained weight changes, wide purple stretch marks, muscle weakness, high blood pressure, and elevated blood sugar occur together.

A comprehensive evaluation performed by Prof. Dr. Ömür Günaldı is important for considering clinical findings and diagnostic tests as a whole in patients with suspected Cushing’s syndrome. An accurate diagnosis, identification of the underlying cause of the condition, and development of an individualized treatment plan form the foundation of a successful treatment process.