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Cushing Syndrome: Causes, Symptoms and Treatment

Cushing syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol in the blood. It can lead to weight gain, high blood pressure, and muscle weakness.

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Things worth knowing about "Cushing Syndrome"

Cushing syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol in the blood. It can lead to weight gain, high blood pressure, and muscle weakness.

What is Cushing Syndrome?

Cushing syndrome is a serious hormonal disorder caused by chronically elevated levels of the stress hormone cortisol in the blood. Cortisol is produced in the adrenal cortex and plays a key role in regulating metabolism, the immune system, and the body's stress response. When the body is exposed to too much cortisol over a prolonged period, either through internal overproduction or external administration, Cushing syndrome can develop.

A distinction is made between endogenous Cushing syndrome, caused by the body's own overproduction of cortisol, and exogenous (iatrogenic) Cushing syndrome, triggered by the long-term use of corticosteroid medications such as prednisone or dexamethasone.

Causes

The causes of Cushing syndrome can be divided into two main groups:

Endogenous Causes

Cushing disease: The most common endogenous cause. A benign tumor of the pituitary gland produces excessive amounts of ACTH (adrenocorticotropic hormone), which stimulates the adrenal glands to produce more cortisol.
Adrenal tumors: Benign or malignant tumors of the adrenal cortex can directly produce excess cortisol.
Ectopic ACTH production: Certain tumors outside the pituitary gland (e.g., lung tumors) can produce ACTH and thereby stimulate the adrenal glands.

Exogenous Causes

Long-term use of corticosteroid medications (e.g., prednisone, dexamethasone) to treat conditions such as asthma, rheumatoid arthritis, or autoimmune diseases.

Symptoms

The symptoms of Cushing syndrome are varied and typically develop gradually. Common signs include:

Weight gain, particularly in the abdomen, face (moon face), and upper back (buffalo hump)
Thin, fragile skin that bruises easily
Purple stretch marks (striae) on the abdomen, thighs, and arms
Muscle weakness and muscle loss, especially in the thighs
High blood pressure (hypertension)
Elevated blood sugar, which can progress to type 2 diabetes
Osteoporosis (bone loss)
Mood swings, depression, and anxiety
Increased susceptibility to infections due to immune suppression
In women: menstrual irregularities and excessive hair growth (hirsutism)
In men: erectile dysfunction and reduced libido

Diagnosis

Diagnosing Cushing syndrome requires several steps:

24-hour urinary cortisol: Measurement of the total cortisol excreted in the urine over 24 hours.
Late-night salivary cortisol: Cortisol levels in saliva are measured late at night, when they are normally lowest but elevated in Cushing syndrome.
Dexamethasone suppression test: A dose of dexamethasone is given to check whether cortisol production can be suppressed.
MRI or CT scan: Imaging to locate tumors in the pituitary gland or adrenal glands.
ACTH blood test: To differentiate between pituitary, adrenal, and ectopic causes.

Treatment

Treatment depends on the underlying cause:

Surgery

For a pituitary tumor (Cushing disease), transsphenoidal pituitary surgery is the preferred treatment. The tumor is removed through the nasal cavity. For adrenal tumors, the affected adrenal gland is surgically removed (adrenalectomy).

Radiation Therapy

When surgery is not possible or the tumor cannot be completely removed, radiation therapy of the pituitary gland may be used as an alternative or supplementary treatment.

Medication

Drugs such as metyrapone, ketoconazole, or osilodrostat can inhibit cortisol production and are used when surgery is not an option or as a bridge therapy before surgery.

Exogenous Cushing Syndrome

If the syndrome is caused by corticosteroid medications, the dose should be gradually reduced under medical supervision. Abruptly stopping corticosteroids is dangerous and can trigger adrenal insufficiency.

Prognosis

With appropriate treatment, many symptoms of Cushing syndrome can be significantly improved or resolved. After successful surgery, cortisol levels often normalize within a few months. Without treatment, however, Cushing syndrome can lead to serious complications including cardiovascular disease, diabetes, and bone fractures.

References

Nieman LK et al. - The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, 2008.
World Health Organization (WHO) - Endocrine Disorders, 2023. Available at: https://www.who.int
Lacroix A et al. - Cushing's syndrome. The Lancet, 2015; 386(9996): 913-927.

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