Cushing Syndrome

Cushing syndrome happens when the body has excessive levels of cortisol for a prolonged period.

Cortisol is a hormone produced and released by the adrenal glands. Often called the “stress hormone,” cortisol regulates stress response, metabolism, immune function, and blood pressure.

With Cushing syndrome, the body produces and releases too much cortisol. This leads to weight gain, fatigue, skin problems, and high blood pressure.

Cushing syndrome can be caused by steroid medications or tumors. Treatment depends on the cause and severity of the problem, but often includes surgery, radiation, medication, or reducing steroid use.

Learn more about Cushing syndrome, including its definition, causes, symptoms, diagnosis, treatment, and potential risks and complications.

What is Cushing syndrome?

Cushing syndrome happens when the body is exposed to high levels of cortisol for an extended period. Cortisol is a hormone critical for maintaining various physiological functions, including metabolism, immune response, and stress response. Overproduction or prolonged exposure to cortisol can lead to a wide range of symptoms.

Causes of Cushing syndrome

Cushing syndrome is caused by an excess of cortisol in the body. Cushing syndrome can be caused by taking certain medicines (called exogenous Cushing syndrome) or by tumors that cause the body to make too much cortisol (called endogenous Cushing syndrome).

Endogenous causes

• Pituitary tumors: Caused by a pituitary adenoma (benign tumor of the pituitary gland) that secretes excess adrenocorticotropic hormone (ACTH), stimulating the adrenal glands to produce more cortisol.
• Adrenal tumors: Adenomas or carcinomas (benign or malignant tumors) of the adrenal glands that produce excess cortisol independently of ACTH regulation.
• Ectopic ACTH syndrome: Non-pituitary tumors (such as small cell lung cancer or carcinoid tumors) that produce ACTH, leading to increased cortisol production by the adrenal glands.

Exogenous causes

Prolonged use of corticosteroid medications: Chronic use of high-dose corticosteroid medications (such as prednisone) for the treatment of inflammatory diseases, autoimmune disorders, or organ transplants can cause iatrogenic Cushing syndrome.

Symptoms of Cushing syndrome

The most commonly noticeable symptom of Cushing syndrome is weight gain in the face, upper back, and abdomen. People with Cushing syndrome may gain weight in these areas while having thin arms and legs. Symptoms include:

• Weight gain: Particularly in the face (moon face), upper back (buffalo hump), and abdominal region.
• Central obesity: Accumulation of fat around the midsection while limbs remain relatively thin.
• Facial changes: Rounded face, often with reddish-purple discoloration.
• Skin changes: Thinning skin, easy bruising, purple stretch marks (striae) on the abdomen, thighs, and breasts.
• Muscle weakness: Proximal muscle weakness, particularly in the thighs and upper arms.
• Bone loss: Osteoporosis, leading to fractures.

Other symptoms

• High blood pressure (hypertension): Persistent elevated blood pressure.
• Glucose intolerance or diabetes: Increased blood sugar levels, potentially leading to diabetes.
• Mood changes: Depression, anxiety, irritability.
• Cognitive changes: Difficulty concentrating, memory impairment.
• Hirsutism: Excessive hair growth in women, particularly on the face, chest, and abdomen.
• Menstrual irregularities: Irregular or absent menstrual periods in women.
• Decreased libido: Reduced sexual desire.
• Fatigue: Generalized tiredness and lack of energy.
• Poor wound healing: Slower recovery from injuries and infections.

Diagnosis of Cushing syndrome

Medical history and physical examination

• Symptom assessment: Detailed inquiry about symptoms such as weight gain, skin changes, muscle weakness, and menstrual irregularities.
• Medical history: Review of risk factors, including prolonged use of corticosteroid medications, family history of endocrine disorders, and presence of tumors.
• Physical examination: Examination focused on identifying characteristic signs of Cushing syndrome, including facial changes, central obesity, skin changes, and muscle weakness.

Diagnostic tests

• Initial screening tests:
  • 24-hour urinary free cortisol test: Measures cortisol levels in urine collected over 24 hours to assess cortisol production.
  • Late-night salivary cortisol test: Measures cortisol levels in saliva late at night when cortisol levels should be at their lowest.
  • Low-dose dexamethasone suppression test (LDDST): Measures cortisol levels after administration of dexamethasone, a synthetic glucocorticoid. Failure to suppress cortisol production indicates Cushing syndrome.
• Confirmatory tests:
  • High-dose dexamethasone suppression test (HDDST): Differentiates between different causes of Cushing syndrome by assessing cortisol response to higher doses of dexamethasone.
  • ACTH measurement: Determines if the cause is ACTH-dependent or ACTH-independent by measuring blood levels of ACTH.
• Imaging studies:
  • MRI of the pituitary gland: Identifies pituitary adenomas causing Cushing’s disease.
  • CT scan or MRI of the adrenal glands: Detects adrenal tumors.
  • CT scan or PET scan: Identifies ectopic ACTH-producing tumors.

Treatment of Cushing syndrome

Cushing syndrome treatment aims to lower the amount of cortisol in the body. Treatment options may include medications, surgery, or radiation. For people who are taking medicine that can cause excessive cortisol, a health care provider may lower the amount of your dosage to control symptoms.

• Medications: Drugs to control cortisol production or block the effects of cortisol, including:
  • Ketoconazole: Antifungal medication that inhibits adrenal cortisol production.
  • Metyrapone: Inhibits cortisol synthesis.
  • Mitotane: Suppresses adrenal gland function, used in adrenal carcinoma.
  • Mifepristone: Blocks cortisol receptors, used for treatment of
• Transsphenoidal surgery: Surgical removal of pituitary adenomas through the nasal passage, typically performed for Cushing’s disease.
• Adrenalectomy: Surgical removal of one or both adrenal glands, indicated for adrenal adenomas or carcinomas.
• Resection of ectopic ACTH-producing tumors: Surgical removal of tumors outside the pituitary gland producing ACTH.
• Pituitary radiation: Used for patients who have residual or recurrent pituitary adenomas after surgery, particularly in Cushing’s disease.
• Stereotactic radiosurgery (Gamma Knife): Focused radiation treatment for pituitary adenomas.

Post-treatment care

• Regular follow-up: Monitoring for recurrence of Cushing syndrome, pituitary or adrenal insufficiency, and overall endocrine function.
• Medication management: Temporary or lifelong hormone replacement therapy may be required if treatment leads to adrenal insufficiency.
• Lifestyle modifications: Dietary adjustments, regular exercise, and management of cardiovascular risk factors to improve overall health and prevent complications.

Potential risks and complications

Complications of untreated Cushing syndrome

• Cardiovascular risks: Increased risk of heart disease, heart attacks, strokes, and hypertension due to prolonged high cortisol levels.
• Metabolic complications: Development of diabetes, obesity, and dyslipidemia.
• Osteoporosis: Increased risk of bone fractures due to bone loss.
• Infections: Weakened immune response and increased susceptibility to infections.
• Psychological impact: Increased risk of depression, anxiety, and other mood disorders.

Long-term considerations

• Ongoing monitoring: Regular follow-up with blood tests to monitor cortisol levels, endocrine function, and detect any recurrence or complications.
• Hormone replacement therapy: Lifelong hormone replacement may be necessary for patients with adrenal insufficiency following treatment.
• Monitoring for recurrence: Regular imaging studies and hormonal evaluations to detect any recurrence of the underlying cause.

Impact on quality of life

• Symptom relief: Effective treatment can alleviate symptoms, normalize cortisol levels, and significantly improve overall well-being and quality of life.
• Informed decision-making: Accurate diagnosis aids in making informed decisions about treatment and preventive measures.
• Emotional support: Providing counseling and support to address anxiety, depression, and the psychological impact of living with Cushing syndrome or undergoing treatment.

Cushing syndrome is a serious condition that can significantly impact multiple organ systems if left untreated. Early diagnosis and appropriate intervention with medical treatments, surgery, or radiation therapy are crucial for managing symptoms and preventing complications. Understanding the causes, symptoms, diagnostic methods, and treatment options is essential for effective management. If you or a loved one are experiencing symptoms or have risk factors for Cushing syndrome, consulting with a health care provider, endocrinologist, or specialized surgeon will help determine the need for further evaluation and develop a suitable treatment plan tailored to your specific needs and circumstances.