Cushing Syndrome: Managing Symptoms and Improving Quality of Life

Characterised by excessive cortisol production, Cushing syndrome may present many symptoms that can significantly impact the quality of life. Understanding Cushing syndrome is essential for individuals affected by this complex hormonal disorder, their caregivers and healthcare providers. In this article, we delve into the intricacies of Cushing syndrome, exploring its underlying causes, diagnostic approaches, and various treatment options to manage symptoms and enhance the overall quality of life for those affected by this condition.

What is Cushing Syndrome?

Cushing syndrome, also known as hypercortisolism, is a hormonal disorder characterised by prolonged exposure to high levels of cortisol, a hormone produced by the adrenal glands. Cortisol is vital in regulating metabolism, immune function, and stress response. However, excessive cortisol production or administration can lead to various signs and symptoms associated with Cushing syndrome. There are two main types of Cushing syndrome: Endogenous and Exogenous Cushing syndrome.

What Causes Cushing Syndrome?

Several factors can cause Cushing syndrome, all of which ultimately lead to excess cortisol in the body. Here are the main causes:

Endogenous Cushing Syndrome

• Pituitary adenoma (Cushing's disease): The most common cause of endogenous Cushing syndrome is a non-cancerous tumour (adenoma) of the pituitary gland, known as Cushing's disease. This tumour generates an overproduction of adrenocorticotropic hormone (ACTH), leading to increased cortisol production by the adrenal glands.
• Adrenal tumours: Tumours in the adrenal glands (adrenal adenomas or carcinomas) can directly produce cortisol, leading to Cushing syndrome. These tumours can be benign or malignant.
• Ectopic ACTH syndrome: Rarely, tumours outside the pituitary or adrenal glands, such as those in the lungs or pancreas, may produce ACTH, resulting in an overproduction of cortisol. This condition is referred to as ectopic ACTH syndrome.

Exogenous Cushing Syndrome

• Long-term corticosteroid use: The most common cause of exogenous Cushing syndrome is the prolonged use of corticosteroid medications, such as prednisone, dexamethasone, or cortisone. These medications are prescribed to treat various medical conditions such as asthma, rheumatoid arthritis, autoimmune disorders, and inflammatory conditions.

In both endogenous and exogenous Cushing syndrome, the excess cortisol disrupts the body's normal functions and metabolism, leading to a wide range of signs and symptoms. Identifying the root cause of Cushing syndrome is important for selecting the most effective treatment strategy.

What are the Symptoms of Cushing Syndrome?

Cushing syndrome is characterised by a variety of signs and symptoms resulting from prolonged exposure to high levels of cortisol in the body. These symptoms can vary in severity and may develop gradually over time. Some common symptoms include:

• Weight gain: Especially around the face (moon face), neck, upper back (buffalo hump), and abdomen (central obesity).
• Skin changes: Thin and fragile skin that bruises easily. Broad purple or pink stretch marks (striae), particularly on the abdomen, thighs, and breasts. Acne or skin infections.
• Muscle weakness and wasting: This condition primarily affects the proximal muscles (arms and legs), making it difficult to lift objects or rise from a seated position.
• Osteoporosis: Weakening of the bones increases the likelihood of fractures, especially in the spinal region and hip joints.
• High blood pressure (Hypertension): Elevated blood pressure is common in individuals with Cushing syndrome.
• Irregular menstrual periods: Women may experience irregular or absent menstrual periods (amenorrhea) or other menstrual abnormalities.
• Decreased libido and erectile dysfunction: Men may experience a decrease in libido and sexual function.
• Mood changes: Such as depression, anxiety, irritability, or mood swings.
• Fatigue and weakness: Persistent fatigue and a sense of weakness can significantly affect everyday tasks and overall well-being.
• Glucose intolerance and diabetes mellitus: Elevated cortisol levels can impair glucose metabolism, leading to insulin resistance and diabetes.
• Cognitive changes: Memory impairment, difficulty concentrating, or confusion may occur in some individuals with Cushing syndrome.

It's important to note that not everyone with Cushing syndrome will experience all of these symptoms, and the severity can vary depending on the underlying cause and individual factors. 

What Tests are Done to Diagnose Cushing Syndrome?

To diagnose Cushing syndrome, healthcare providers typically conduct a series of tests to measure cortisol levels, identify the underlying cause, and evaluate the impact of excess cortisol on the body. Here are some common tests used in the diagnostic process:

• Basal Cortisol Test: A basal cortisol done in the morning helps rule in/rule out Exogenous Cushing's syndrome.
• 24-hour Urinary Free Cortisol (UFC) test: This test measures the amount of cortisol released in the urine during a 24-hour timeframe. Excessive urinary cortisol levels suggest Cushing syndrome. This test is often used as an initial screening test due to its convenience and reliability.
• Late-night salivary cortisol test: Cortisol levels normally decrease in the evening and reach their lowest point at night. However, in Cushing syndrome, cortisol levels may remain elevated during the late-night hours. This test involves collecting a saliva sample before bedtime to measure cortisol.
• Overnight Dexamethasone Suppression Test (ONDST): In this test, the individual takes a low dose of dexamethasone, a synthetic corticosteroid, orally once at night. Blood or urine samples are then collected the following day to measure cortisol levels. Usually, cortisol production is suppressed by dexamethasone, but in Cushing syndrome, cortisol levels remain elevated.
• Low Dexamethasone Suppression Test (LDDST): This is a prolonged version of the ONDST wherein the blood cortisol levels are done after 8 doses of low dose dexamethasone given at regular intervals.
• High-Dose Dexamethasone Suppression Test (HDDST): Similar to LDDST, this test involves administering a higher dose of dexamethasone to further suppress cortisol production. Blood or urine samples are collected the next day to measure cortisol levels. Failure to suppress cortisol production indicates Cushing syndrome.
• ACTH level: This test helps differentiate between pituitary-dependent/ectopic causes and adrenal causes of Cushing syndrome. Synthetic ACTH (cosyntropin) is administered, and cortisol levels are measured before and after to assess the adrenal glands' response. In Cushing's disease (pituitary-dependent Cushing syndrome), cortisol production increases in response to ACTH stimulation. In other forms of Cushing syndrome, cortisol production may not increase significantly.
• Circadian rhythm of cortisol and ACTH: This test helps differentiate between pituitary-dependent and ectopic causes of Cushing syndrome.
• Imaging studies: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans may be performed to visualise the pituitary gland and adrenal glands. These imaging studies help identify tumours or other abnormalities causing Cushing syndrome.
• Inferior Petrosal Sinus Sampling (IPSS): This specialised procedure is used to lateralise the pituitary adenoma in cases of Cushing's disease. A catheter is inserted into the veins draining the pituitary gland, and blood samples are collected to measure ACTH levels from both the inferior petrosal sinuses. This test helps localise the source of excess ACTH production.

How is Cushing Syndrome Treated?

The approach to treating Cushing syndrome varies based on its root cause and may include a mix of medication, surgery, and changes in lifestyle. The primary goals of treatment are to normalise cortisol levels, alleviate symptoms, and address any complications associated with the condition. Here are some common treatment approaches:

Surgical Intervention

• Transsphenoidal surgery: This procedure is the treatment of choice for Cushing's disease, the most common form of endogenous Cushing syndrome caused by a pituitary adenoma. During transsphenoidal surgery, the tumour is removed through the nose or sinuses, typically resulting in the normalisation of cortisol levels if successful.
• Adrenalectomy: For cases of Cushing syndrome caused by adrenal tumours (adrenal adenomas or carcinomas), surgical removal of the affected adrenal gland(s) may be necessary. This procedure aims to eliminate excess cortisol production.

Medication

• Steroidogenesis inhibitors: Drugs such as ketoconazole, metyrapone, and mitotane can inhibit cortisol synthesis in the adrenal glands, helping to lower cortisol levels. These medications may be used temporarily to control symptoms before surgery or in cases where surgery is not feasible.
• Pituitary-directed medications: In cases of Cushing's disease that cannot be managed with surgery, medications such as pasireotide or cabergoline may be used to suppress ACTH production by the pituitary gland, thereby reducing cortisol secretion.

Radiation Therapy

• Pituitary radiation: Radiation therapy may be recommended following unsuccessful pituitary surgery or in cases where surgical intervention is not possible. Radiation helps shrink or destroy pituitary tumours, reducing excess ACTH production and cortisol secretion.

Lifestyle Modifications

• Healthy diet: Adopting a balanced diet low in sodium and refined sugars can help manage weight gain and associated metabolic complications.
• Regular exercise: Regular exercise can enhance muscle strength, increase bone density, and boost overall health.
• Stress management: Using stress reduction methods like mindfulness, relaxation exercises, and counselling can help lower the effects of chronic stress on cortisol levels.

Monitoring and Follow-up

Individuals with Cushing syndrome require regular monitoring to assess cortisol levels, evaluate treatment response, and detect any recurrence of symptoms or complications. Close collaboration with an endocrinologist and other healthcare providers is essential for ongoing management and support.

Note: In cases of exogenous Cushing syndrome caused by long-term corticosteroid use, the dosage of corticosteroid medications should be gradually reduced under medical supervision to avoid adrenal insufficiency and withdrawal symptoms.

Conclusion

Navigating the complexities of Cushing syndrome requires a comprehensive understanding and personalised management strategies tailored to each individual's unique circumstances. That said, effective management often requires the expertise of experienced specialists who can provide specialised care and guidance throughout the treatment journey. That's when you can count on the expertise of Max Hospitals. Our dedicated team of Endocrinologists and multidisciplinary healthcare professionals is committed to empowering patients to regain control of their health and achieve optimal outcomes. Take the first step towards managing Cushing syndrome effectively by scheduling a consultation with the Endocrinology experts at Max Hospitals. 

Frequently Asked Questions

1. What are the effects of Cushing's syndrome on the quality of life?

Cushing's syndrome can significantly impact quality of life due to its various symptoms, such as weight gain, fatigue, muscle weakness, mood changes, and impaired cognitive function. These symptoms can affect physical, emotional, and social well-being, resulting in decreased quality of life and functional impairment.

2. Is Cushing syndrome fatal?

Untreated or poorly controlled Cushing syndrome can lead to serious complications, including cardiovascular disease, diabetes mellitus, osteoporosis, infections, and psychiatric disorders. In severe cases, complications such as adrenal crises or cardiovascular events can be life-threatening. However, with appropriate treatment and management, the prognosis for individuals with Cushing syndrome can be improved.

3. Does Cushing syndrome cause shortness of breath?

Yes, Cushing syndrome can cause shortness of breath due to various factors, including obesity, weakened respiratory muscles, fluid retention, and cardiovascular complications such as hypertension and heart failure. Additionally, compression of the lungs by a large abdominal or thoracic fat pad (buffalo hump) can contribute to breathing difficulties.

4. Is Cushing syndrome genetic?

While most cases of Cushing syndrome are not inherited and occur sporadically due to factors such as pituitary or adrenal tumours or exogenous corticosteroid use, there are rare genetic syndromes associated with the development of cortisol-secreting tumours, such as familial Cushing syndrome.

5. Who treats Cushing syndrome?

Cushing syndrome is managed primarily by Endocrinologists, who specialise in hormonal disorders, particularly those affecting the adrenal glands and pituitary gland. Depending on the underlying cause and associated complications, other healthcare providers such as neurosurgeons, oncologists, and radiologists may also be involved in the treatment and management of Cushing syndrome.

6. Does Cushing syndrome cause osteoporosis?

Yes, chronic exposure to high levels of cortisol in Cushing syndrome can lead to decreased bone density and increased risk of osteoporosis. Cortisol has catabolic effects on bone tissue, inhibiting bone formation and promoting bone resorption, which can result in bone loss and increased fracture risk.

7. Does Cushing syndrome cause hypokalemia?

Hypokalemia (low potassium levels) can occur in Cushing syndrome, particularly in cases of excessive cortisol production by ectopic tumours. Cortisol promotes potassium excretion by the kidneys, leading to potassium depletion and hypokalemia. However, hypokalemia may not be present in all cases of Cushing syndrome and can vary depending on the underlying cause and individual factors.

8. How can the risk of Cushing syndrome be reduced or prevented?

Since Cushing syndrome can have various underlying causes, prevention strategies depend on the specific risk factors involved. For instance, individuals using corticosteroid medications should follow their healthcare provider's recommendations regarding dosage and duration of treatment to minimise the risk of developing exogenous Cushing syndrome. Regular monitoring and early detection of adrenal or pituitary tumours can also help prevent complications associated with endogenous Cushing syndrome.