Cushing syndrome, also known as hypercortisolism, is a rare endocrine disorder characterized by prolonged exposure to excessive levels of the hormone cortisol. Cortisol, often referred to as the “stress hormone,” plays a vital role in regulating various bodily functions, including blood pressure, blood sugar, inflammation, memory formation, respiration, and energy production. While cortisol is essential for maintaining overall health, an overabundance of this hormone can lead to a constellation of symptoms, collectively known as Cushing syndrome.
Understanding Cushing Syndrome
Cushing syndrome can arise from both endogenous (internal) and exogenous (external) factors. Endogenous Cushing syndrome occurs when the body produces too much cortisol on its own, often due to tumors in the pituitary gland (Cushing's disease), adrenal glands, or other organs that produce ACTH (adrenocorticotropic hormone). Exogenous Cushing syndrome, on the other hand, is caused by the prolonged use of glucocorticoid medications, such as prednisone, which are commonly prescribed to treat inflammatory conditions like rheumatoid arthritis, lupus, and asthma.
Causes of Cushing Syndrome
Several factors can contribute to the development of Cushing syndrome, including:
- Glucocorticoid Medications (Exogenous Cushing Syndrome): Prolonged use of glucocorticoid medicines to treat inflammatory diseases. These medicines may be taken by mouth, given as a shot, rubbed into the skin, or breathed into the lungs by an inhaler.
- ACTH-Producing Pituitary Adenoma (Cushing's Disease): Pituitary adenomas are tumors that grow in the pituitary gland. They sometimes make too much ACTH, causing the adrenal glands to make extra cortisol. When Cushing syndrome happens this way, it's called Cushing disease.
- Ectopic ACTH-Producing Tumor: Rarely, a tumor that makes too much ACTH grows in an organ that usually doesn't make ACTH. This is called ectopic ACTH production. It causes the body to make too much cortisol.
- Adrenal Gland Tumors or Disease: Problems with the adrenal glands can cause them to make too much cortisol. The most common is a tumor in the outer part of the adrenal gland called an adrenal adenoma. Cancerous tumors in the outer part of the adrenal glands, known as adrenocortical carcinoma, are rare, but they can make cortisol and cause Cushing syndrome.
- Familial Cushing Syndrome: Rarely, people inherit a tendency to get tumors on one or more of their endocrine glands, which are glands that make hormones.
Who is Affected?
Cushing syndrome primarily affects children, teenagers, and adults, particularly those between the ages of 25 and 50. Individuals who take cortisol medication are especially vulnerable. Women are more likely to develop Cushing syndrome than men, with approximately 70% of cases occurring in women and 30% in men.
Prevalence
Cushing syndrome is a rare condition, affecting an estimated 40 to 70 people per million each year.
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Cushing Syndrome vs. Cushing Disease
Cushing disease is a specific type of Cushing syndrome caused by a benign tumor in the pituitary gland that secretes excessive amounts of ACTH. This, in turn, leads to increased cortisol secretion from the adrenal glands. Cushing disease accounts for over 70% of Cushing syndrome cases in adults and approximately 60% to 70% of cases in children and adolescents.
Symptoms of Cushing Syndrome
The symptoms of Cushing syndrome can vary depending on the severity and duration of cortisol excess. Common signs and symptoms include:
- Weight gain: Progressive weight gain associated with central adiposity is a common manifestation of CD occurring during the early stage of the disease. Rapid weight gain is the most common symptom associated with Cushing's syndrome.
- A fatty lump between the shoulders: Too much cortisol can cause some of the main symptoms of Cushing syndrome - a fatty hump between the shoulders.
- Rounded face: Too much cortisol can cause some of the main symptoms of Cushing syndrome - a rounded face.
- Pink or purple stretch marks on the skin: Too much cortisol can cause some of the main symptoms of Cushing syndrome - pink or purple stretch marks on the skin.
- High blood pressure: Cushing syndrome also can cause high blood pressure.
- Bone loss: Cushing syndrome also can cause bone loss.
- Thick, dark hair on the face and body: Thick, dark hair on the face and body.
Other common symptoms include:
- Hypertension
- Diabetes
- Cardiac hypertrophy
- Arterial and venous thrombosis
- Electrolyte abnormalities
- Psychiatric disturbances
- Proximal myopathy
- Facial plethora
- Easy bruising
- Wide striae
In rare cases, Cushing's disease (CD) typically present with weight gain, whereas weight loss and hypokalemia in endogenous Cushing’s patients are suggestive of ectopic ACTH production.
The Link Between Cushing Syndrome and Weight Changes
While weight gain, particularly in the abdominal area, is a hallmark of Cushing syndrome, some individuals may experience weight loss, especially in cases of ectopic ACTH production or underlying malignancies.
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Weight Gain in Cushing Syndrome
Chronic hypercortisolemia is associated with increased abdominal adiposity, which is thought to be caused by the downregulation of adenosine monophosphate-activated protein kinase (AMPK), responsible for regulating lipid metabolism. Glucocorticoids also induce a direct orexigenic effect, leading to weight gain.
Weight Loss in Cushing Syndrome
Weight loss in association with hypercortisolemia can be a presenting feature of ectopic ACTH-producing tumors, such as small cell lung cancer. The underlying mechanism of weight loss is thought to be partly due to cAMP/Protein kinase A (PKA) pathway activation, with an increase in PKA activity resulting in altered downstream regulation of cAMP-related lipogenic and lipolytic proteins. High ACTH secretion and the malignant characteristics of the neoplastic process are also thought to play roles in weight loss.
Dietary Strategies for Managing Cushing Syndrome
While medical treatments are essential for addressing the underlying cause of Cushing syndrome, dietary modifications can play a crucial role in managing symptoms and improving overall well-being.
Key Dietary Recommendations
- Vitamin D-Rich Foods: The sunshine vitamin is packed inside foods like fatty fish, mushrooms, and some cereals.
- Limit Sugary and Processed Foods: Avoid sugary and processed foods and snacks to keep your blood sugar and weight gain in check. Pick high-fiber foods rich in carbohydrates with lower glycemic levels.
- Reduce Sodium Intake: Skip the salty processed stuff and stick with natural choices like fresh fruits, veggies, eggs, lean meats like chicken and fish, and homemade soups.
- Increase Protein Intake: People with Cushing syndrome may have thinner arms and legs due to reduced muscle mass. Eating enough protein can help keep your muscles in good shape.
- Stay Hydrated: Staying hydrated helps your body work better and prevents fluid buildup.
Healthy Meal Choices
A balanced diet for individuals with Cushing syndrome should include:
- Calcium-rich foods
- High-fiber options
- Lean protein sources
- Limited amounts of salt and sugar
Medical Treatments for Cushing Syndrome
Treatments for Cushing syndrome aim to lower the body's cortisol levels and alleviate symptoms. Treatment options may include:
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- Surgery: Surgeons first try to treat the disease by removing the tumor.
- Medications: Mifepristone (Korlym), a glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery.
The Role of Mifepristone in Weight Management
Mifepristone, a glucocorticoid receptor antagonist, has shown promise in managing weight and improving metabolic parameters in patients with Cushing syndrome.
Clinical Evidence
A long-term safety extension (LTE) study of mifepristone demonstrated that clinically meaningful weight loss (≥5% of body weight) achieved during short-term mifepristone use was sustained in approximately 80% of patients with CS who were treated with mifepristone for up to 3.5 years. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit.
Benefits of Weight Loss
A weight loss of 5-10 % has been shown to reduce cardiovascular risk factors in other at-risk populations.
Potential Adverse Events
Long-term therapy with mifepristone in patients with CS was associated with an AE profile comparable to that reported in the 24-week SEISMIC study. The most common AEs reported were nausea (52 %), decreased blood potassium (48 %), fatigue (45 %), headache (38 %), and endometrial thickening (35 %).