Cushing Syndrome

Cushing's syndrome is an endocrine disorder caused by prolonged exposure to high levels of cortisol. Cortisol is a hormone produced by the adrenal glands and is essential for regulating metabolism, immune response, and stress response.

Epidemiologically, Cushing's syndrome is relatively rare, with an estimated incidence of about 10 to 15 cases per million people per year. The disorder is more common in women than men, with a ratio of approximately 3:1, and is usually diagnosed in individuals aged 20 to 50 years.

The pathophysiology of Cushing's syndrome involves the overproduction of cortisol. This can result from either endogenous or exogenous factors. Endogenous causes include adrenal hyperplasia or tumors, Cushing's disease caused by a pituitary adenoma that secretes adrenocorticotropic hormone (ACTH), and ectopic ACTH-secreting tumors. Exogenous causes involve the prolonged use of glucocorticoid medications to treat other conditions.

The causes of Cushing's syndrome vary. The most common causes include Cushing's disease, which accounts for about 70% of cases, adrenal hyperplasia or tumors, and the prolonged use of glucocorticoid medications. Other causes may include ectopic ACTH-producing tumors.

The symptoms of Cushing's syndrome include weight gain, particularly in the face (moon face), neck (buffalo hump), and abdominal area, thin and fragile skin that bruises easily, purple striae on the abdomen, muscle weakness, hypertension, hyperglycemia, osteoporosis, and mood disorders such as depression and anxiety.

The differential diagnosis of Cushing's syndrome involves excluding other conditions that may cause similar symptoms, such as obesity, metabolic syndrome, hypothyroidism, and other endocrine disorders. These conditions are collectively referred to as pseudo-Cushing syndrome (PCS). Individuals with pseudo-Cushing may have both clinical features and initial biochemical evaluation results that are suggestive of Cushing's syndrome. However, these individuals do not have endogenous pathologic hypercortisolism. Causes of pseudo-Cushing syndrome may include morbid obesity, extreme exercise, stress, hypertension, pregnancy (in the second or third trimester), alcohol use disorder, uncontrolled diabetes mellitus, polycystic ovary syndrome (PCOS), eating disorders, and certain psychiatric disorders such as depression. If a patient has one of these conditions, treating the condition and reassessing cortisol concentrations may help identify PCS.

Complications of Cushing's syndrome are severe and can include cardiovascular diseases such as hypertension and heart failure, diabetes mellitus, infections due to immune suppression, osteoporosis with an increased risk of fractures, and psychiatric disorders such as depression and psychosis.

Treatment of Cushing's syndrome depends on the cause of hypercortisolism. In cases of endogenous Cushing's syndrome due to a pituitary adenoma, surgical removal of the tumor is the preferred treatment. If there are adrenal tumors, removal of the affected adrenal gland may be necessary. For patients who are not surgical candidates or those whose surgical treatment is not successful, medications are available that reduce cortisol production. In cases of exogenous Cushing's syndrome due to the use of glucocorticoid medications, gradual tapering of the drug dose may be necessary.

Laboratory tests are crucial for the diagnosis and monitoring of Cushing's syndrome. Initial diagnosis involves measuring cortisol levels in the blood, urine, and saliva. The 24-hour urine free cortisol test is one of the most reliable methods for diagnosing the condition. Measuring late-night salivary cortisol levels can also be used, as normal cortisol secretion follows a circadian rhythm, and levels are low at night. The dexamethasone suppression test is also helpful. In this test, administering a low dose of dexamethasone at night does not suppress morning blood cortisol levels in patients with Cushing's syndrome.

Further tests include measuring ACTH levels to differentiate whether Cushing's syndrome is due to ACTH overproduction or autonomous cortisol production from the adrenal glands. Imaging studies such as magnetic resonance imaging (MRI) or computed tomography (CT) can reveal the presence of a pituitary or adrenal tumor.

After treatment, monitoring patients with Cushing's syndrome involves regular clinical assessments and laboratory tests to monitor endocrine function and detect possible relapses. Patients who have undergone surgical removal of a pituitary adenoma or adrenal tumors need close monitoring for any recurrence of symptoms and changes in cortisol levels.

Additionally, patients who have undergone surgical treatment may require hormone replacement therapy, especially if they have developed pituitary or adrenal insufficiency as a result of the treatment. Monitoring thyroid function and other endocrine glands is also essential, as pituitary insufficiency can affect the production of other hormones.

Regular assessment of blood pressure, blood sugar, and lipid levels is crucial for monitoring the long-term complications of Cushing's syndrome, such as hypertension, diabetes mellitus, and dyslipidemia. Bone density evaluation through dual-energy X-ray absorptiometry (DEXA) is also necessary to detect and manage osteoporosis.

Continuous psychological support and monitoring of mental health are also crucial for addressing psychiatric symptoms and improving the quality of life of patients. Patients with Cushing's syndrome often face significant mood changes and cognitive disorders.

This article belongs to a new series on our blog that covers all fields of health! We present information on the most frequent pathological conditions in a comprehensive, clear, understandable, but always scientifically documented way so you can know and protect the most crucial good: your health!

Ioannis Sideris, Medical Doctor