Symptoms of Cushing's Disease

Cushing's disease, also known as hypercortisolism or hyperadrenocorticism, is a rare endocrine disorder characterized by excessive production of cortisol, a hormone produced by the adrenal glands. The condition is named after the famous neurosurgeon Harvey Cushing, who first described it in the early 20th century.

The primary cause of Cushing's disease is usually a benign tumor called an adenoma located in the pituitary gland. The pituitary gland is a small gland located at the base of the brain, and it plays a crucial role in regulating the body's hormonal functions.

The adenoma in Cushing's disease causes the pituitary gland to produce an excessive amount of adrenocorticotropic hormone (ACTH), which, in turn, stimulates the adrenal glands to produce more cortisol than the body needs.

Cortisol production naturally follows a daily cycle, known as the 'circadian rhythm.' This hormone exhibits its highest levels in the morning, promoting wakefulness, and gradually decreases during the night to support a restful sleep.

Additionally, cortisol is produced in response to acute stress, triggering the well-known "fight or flight" response. In both situations, cortisol plays a vital role in regulating blood pressure, mobilizing energy reserves, and temporarily suppressing the immune system to deal with immediate challenges.

However, problems arise when this stress response remains chronically active, leading to disruptive symptoms. In this article, we will describe the symptoms of Cushing’s disease and answers to commonly asked questions.

The range and severity of symptoms depend on factors such as the activity level of the pituitary tumor, the duration of cortisol excess, and individual differences in how the body responds to the hormone.

Some individuals may have mild symptoms, while others may experience more pronounced effects. Common symptoms include:

• Excess hair growth
• Redness of the cheeks
• Abdominal weight gain
• Muscle loss, particularly of arms and legs
• Round, fuller appearing face
• Weakness and fatigue
• Mood disorders
• Diabetes mellitus (Type 2)
• Elevated blood pressure
• Fat accumulation on the back of the neck
• Abdominal stretch marks and easy bruising
• Decreased fertility
• Osteoporosis
• Macroadenomas, which are very large pituitary tumors, can give rise to additional symptoms due to their compression of nearby structures. Their proximity to the optic nerve fibers can cause visual disturbances, notably a loss of peripheral vision known as bitemporal hemianopsia.

Besides ACTH, the pituitary gland produces thyroid, growth, and sex hormones. When a sizable pituitary adenoma compresses the normal pituitary gland, it can lead to decreased levels of these critical hormones and trigger specific symptoms. For instance, reduced sex hormone levels may result in a diminished sexual drive and infertility.

While symptoms of Cushing's disease can present similarly in both females and males, there are some differences in the manifestation of certain symptoms by gender.

Specific symptoms that are unique or more pronounced to females include absent menstruation, and excessive hair growth on the face, chest, or abdomen. Men with Cushing's disease may experience erectile dysfunction and decreased libido due to alteration in testosterone levels.

Advanced symptoms of Cushing's disease may occur when the condition remains untreated or undiagnosed for an extended period. When this happens, the multitude of symptoms related to Cushing's disease are most prominent and severe complications can occur.

Complications related to Cushing's disease include the following:

• Cardiovascular complications: Elevated cortisol levels can lead to high blood pressure (hypertension), hardening and narrowing of the arteries (atherosclerosis), irregular heart rhythms (arrhythmia), diseases of the heart muscle (cardiomyopathy), and increased risk of heart attack and stroke.
• Metabolic disturbances: Chronic levels of excess cortisol can lead to glucose intolerance, insulin resistance, and ultimately, diabetes. It can also disrupt lipid metabolism. Both can increase the risk of cardiovascular disease.
• Osteoporosis and bone fractures: Prolonged exposure to high levels of cortisol can lead to decreased bone density and increased risk of osteoporosis, resulting in bone fragility and susceptibility to fractures.
• Immunosuppression: Excess cortisol can suppress the immune system, making individuals more susceptible to infection. This can lead to recurrent infections, delayed wound healing, and increased risk of secondary infections.
• Psychological and emotional impact: Cushing's disease can cause mood swings, depression, anxiety, irritability, cognitive impairment, and other psychological and emotional disturbances. These symptoms can significantly impact quality of life and may require psychological support and intervention.
• Musculoskeletal complications: Muscle weakness, wasting, and fatigue are common in Cushing's disease, leading to reduced physical function and mobility. Individuals may experience difficulty performing daily activities and be at an increased risk of fall and injuries.
• Reproductive issues: In women, Cushing's disease can cause menstrual irregularities including absence or infrequent menstruation. In men, it can lead to decreased libido and erectile dysfunction.

Prevention of complications through prompt diagnosis and treatment is critical. Treatment typically involves surgery to remove the underlying pituitary tumor. In some cases, radiation therapy and medications may be used.

Cushing's disease can initially present with subtle symptoms that may not significantly impact how you feel. However, as the disease progresses, you may begin to experience increasing fatigue, anxiety, irritability, and weight gain.

Bringing these symptoms to the attention of your healthcare provide during a routine health examination could be the initial step in identifying and diagnosing Cushing's disease.

Diagnosing Cushing's disease involves a series of steps, including a review of your medical, a physical examination, and laboratory tests. A physical examination and identification of Cushing's syndrome signs will prompt more specific laboratory tests to confirm the diagnosis.  

Laboratory testing for Cushing's disease involves measuring hormone levels in blood, urine, or saliva samples to assess cortisol production and its regulation. Here are the main laboratory tests used in the diagnosis of Cushing's disease:

• 24-hour urinary excretion of cortisol: This test measures the amount of cortisol excreted in the urine over a 24-hour period. Elevated levels of urinary cortisol may indicate Cushing's syndrome. However, other conditions, such as stress or depression, can also lead to elevated cortisol levels, so additional testing is usually necessary for confirmation.
• Late-night salivary cortisol: Measuring cortisol levels in saliva at midnight helps diagnose Cushing syndrome. A negative result suggests the absence of Cushing's syndrome.
• Low-dose dexamethasone suppression test: In this test, a low dose of the synthetic glucocorticoid dexamethasone is given orally at night, and cortisol levels are measured the next morning. Normally, cortisol levels should be suppressed in response to dexamethasone. Failure to suppress cortisol production suggests Cushing's syndrome
• High-dose dexamethasone suppression test: This test is used if the low-dose test is abnormal. It helps differentiate between a pituitary adenoma and an ectopic tumor as the source of elevated cortisol.
• Pituitary Magnetic Resonance Imaging (MRI): Detailed brain imaging to check for a pituitary adenoma once other causes of high cortisol are ruled out.
• Inferior Petrosal Sinus Sampling (IPSS): A procedure that involves placement of a catheter into a vein located at the base of the skull near the pituitary gland (inferior petrosal sinus). The vein drains blood from the pituitary gland and surrounding areas.
  • Blood samples are collected from both sides of the pituitary gland and compared with blood from a peripheral vein, such as in the arm. By comparing ACTH levels obtained from the inferior petrosal sinus and a peripheral vein, clinicians can determine whether the source of ACTH production is localized to the pituitary gland or originates from elsewhere in the body.

Yes, it is possible to have Cushing's disease and be "skinny" or have a normal body weight. While weight gain is a common symptom of Cushing's disease, not all individuals with the condition will experience significant weight changes, especially in the early stages.

Cushing's disease can affect people differently, and the extent of symptoms can vary from person to person. Some individuals may exhibit classic signs of Cushing's disease, such as weight gain, a round face, and central obesity, while others may present with less apparent symptoms or even weight loss.

• Cushing's disease is a rare condition caused by a pituitary adenoma (tumor) that leads to excessive production of cortisol, a hormone produced by the adrenal glands.
• Advanced symptoms of Cushing's disease may occur when the condition remains untreated or undiagnosed.
• Three signs or manifestations of Cushing’s disease include: unexplained weight gain, muscle weakness, and persistent fatigue.
• Diagnostic tests involve measuring cortisol levels in blood, urine, or saliva, along with imaging studies like an MRI.

• Endocrine Society
• Pituitary Foundation
• Urology Care Foundation
• National Adrenal Diseases Foundation