Symptoms of Cushing's Disease

Cushing's disease, also known as hypercortisolism or hyperadrenocorticism, is a rare endocrine disorder caused by a pituitary adenoma (a benign tumor). This tumor triggers an overproduction of ACTH (adrenocorticotropic hormone), which signals the adrenal glands to release excessive cortisol. Known as the "stress hormone," chronic cortisol elevation disrupts the body’s circadian rhythm, blood pressure, and metabolism.

The primary cause of Cushing's disease is usually a benign tumor called a pituitary adenoma located in the pituitary gland. 

The adenoma 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.

The severity of Cushing’s symptoms depends on the pituitary tumor's activity, the duration of cortisol excess, and individual differences in how the body responds to the hormone. Common symptoms include:

• Moon Face: A round, full-appearing face, accompanied by redness of the cheeks
• Buffalo Hump: Fat accumulation on the back of the neck
• Central Obesity: Abdominal weight gain with purple stretch marks and easy bruising
• Hirsutism: Excess hair growth on the face or body
• Fatigue: Profound weakness and persistent tiredness

• Metabolic: Type 2 diabetes and elevated blood pressure
• Musculoskeletal: Muscle loss (thinning arms/legs) and osteoporosis
• Psychological: Mood swings, severe anxiety, depression, and brain fog

• Visual disturbances: Loss of peripheral vision known as bitemporal hemianopsia
• Hormonal Imbalance: Compression of the pituitary can decrease thyroid, growth or sex hormones, leading to diminished sexual drive and infertility.

While Cushing's disease can present similarly in both females and males, the symptoms of high cortisol levels in males can differ from those in females.

• Absent menstruation
• Excessive hair growth on the face, chest, or abdomen

• Erectile dysfunction
• Decreased libido

Mild Cushing’s syndrome, also known as subclinical Cushing’s syndrome or mild hypercortisolism, is a condition of excessive cortisol secretion, without the specific symptoms of Cushing's disease (i.e., proximal muscle weakness, facial plethora, easy bruising, purple striae).

• Thin Skin
• Acne
• Hirsutism
• Poor wound healing
• Obesity
• Peripheral edema (swelling)
• Facial fullness
• Buffalo hump

• Hypertension
• Bone fragility and increased risk of fractures
• Significant mood alterations and emotional instability
• Alterations in glucose (diabetes risk) and lipid metabolism

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.

• Cardiovascular complications: Hypertension, atherosclerosis, arrhythmia, cardiomyopathy, and increased risk of stroke or heart attack
• Metabolic disturbances: Glucose intolerance, insulin resistance, diabetes, disrupted lipid metabolism, increased risk of cardiovascular disease.
• Osteoporosis and bone fractures: Decreased bone density, bone fragility, and susceptibility to fractures.
• Immunosuppression: Increased susceptibility to infection, recurrent infections, delayed wound healing, and increased risk of secondary infections.
• Psychological and emotional impact: Mood swings, depression, anxiety, irritability, cognitive impairment. These symptoms can significantly impact quality of life and may require psychological support and intervention.
• Musculoskeletal complications: Muscle weakness, wasting, fatigue, reduced physical function and mobility, difficulty performing daily activities, increased risk of falls 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.

Diagnosing Cushing's disease involves a series of steps, including a review of your medical history, a physical examination, and laboratory tests. 

• 24-hour urinary excretion of cortisol: This test measures the amount of cortisol excreted in the urine over a 24-hour period. 
• Late-night salivary cortisol: Measuring cortisol levels in saliva at midnight to check if cortisol levels drop at night as they should in a healthy circadian rhythm.
• Low-dose dexamethasone suppression test: Measuring cortisol levels in the morning after giving a low oral dose of synthetic glucocorticoid dexamethasone at night. Cortisol levels should be suppressed in response to dexamethasone.
• 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 to 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. Cushing's disease can affect people differently, especially in the early stages. Some individuals may experience 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.

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• 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.

Cortisol levels rise due to three main factors:

• Natural Rhythms: Your body peaks cortisol in the morning for wakefulness and lowers it at night for sleep (circadian rhythm).
• Acute Stress: The "fight or flight" response temporarily spikes cortisol to manage immediate threats.
• Cushing’s Disease: A benign pituitary tumor (adenoma) triggers a constant, excessive release of ACTH, forcing the adrenal glands to overproduce cortisol.

Living with Cushing's disease feels like a significant and often overwhelming disruption to both your body and mind. The experience is defined by:

• Debilitating Fatigue: A persistent, heavy tiredness that rest cannot fix, often accompanied by muscle weakness that makes daily tasks difficult.
• Emotional Instability: Frequent mood swings, anxiety, irritability, and depression caused by hormonal shifts.
• Brain Fog: Difficulty concentrating and memory issues that impact daily productivity.
• Fragility: Feeling delicate due to thinning skin that bruises easily and weakened bones that increase the risk of fractures.
• Loss of Self: Significant weight gain in the face and torso can lead to feelings of isolation and a sense of losing one's physical identity.

• Endocrine Society
• Pituitary Foundation
• Urology Care Foundation
• National Adrenal Diseases Foundation
• National Library of Medicine