From the Guidelines
Cushing's syndrome is a medical condition caused by excessive levels of cortisol in the body over an extended period, leading to a constellation of classic symptoms and signs, including weight gain, abdominal striae, hirsutism, and hypertension, as described in the 2021 consensus guideline update 1.
Definition and Causes
Cushing's syndrome occurs when the body produces too much cortisol or when someone takes high doses of corticosteroid medications for a long time. The condition can be caused by a tumor in the pituitary gland (Cushing's disease), adrenal gland tumors, or long-term use of corticosteroid medications like prednisone. According to the 2018 scientific statement from the American Heart Association 1, Cushing syndrome is a relatively uncommon endocrine disorder caused by chronic excessive glucocorticoid exposure from endogenous or exogenous sources.
Symptoms and Diagnosis
Symptoms of Cushing's syndrome include weight gain (especially in the face, causing a "moon face" appearance), fatty deposits between the shoulders creating a "buffalo hump," purple stretch marks on the skin, high blood pressure, muscle weakness, and mood changes. Diagnosis involves laboratory tests, imaging, and physical examination. The 2021 consensus guideline update 1 provides recommendations for screening and diagnosis, including the use of laboratory tests and imaging studies.
Treatment and Management
Treatment depends on the cause of Cushing's syndrome but may include:
- Surgery to remove tumors
- Radiation therapy
- Gradually reducing corticosteroid medications under medical supervision
- Medical therapies, such as metyrapone or ketoconazole, to reduce cortisol levels, as recommended in the 2024 consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1
- Pituitary radiotherapy, as recommended in the 2024 consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1
Complications and Quality of Life
If left untreated, Cushing's syndrome can lead to serious complications, including diabetes, bone loss, and increased risk of infections. Early diagnosis and treatment are essential to prevent these complications and improve quality of life. The 2021 consensus guideline update 1 emphasizes the importance of long-term management to optimize patient outcomes.
From the Research
Definition and Causes of Cushing's Syndrome
- Cushing's syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology 2
- The most frequent cause of Cushing's syndrome is exogenous steroid use, but the estimated incidence of Cushing's syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually 2
- Cushing's disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing's syndrome due to endogenous cortisol production 2
Clinical Presentation of Cushing's Syndrome
- Cushing's syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders 2
- Characteristic skin changes include facial plethora, easy bruising, and purple striae, while metabolic manifestations include hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs 2
Diagnosis and Evaluation of Cushing's Syndrome
- Evaluation of patients with possible Cushing's syndrome begins with ruling out exogenous steroid use 2
- Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose 2
- Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism and corticotropin-dependent forms of hypercortisolism 2
Management and Treatment of Cushing's Syndrome
- Management of Cushing's syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers 2
- First-line therapy for Cushing's syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor 2
- Medical therapy is currently adjunctive in most patients with Cushing's disease and is generally prescribed to patients who are about to receive radiation therapy and will be awaiting its salutary effects to occur 3
- Available treatment options include steroidogenesis inhibitors, centrally acting agents, and glucocorticoid receptor antagonists 3, 4, 5, 6