Signs and Symptoms of Cushing's Syndrome
The most characteristic signs and symptoms of Cushing's syndrome include rapid weight gain with central obesity, "moon face," dorsal and supraclavicular fat pads, wide (1-cm) violaceous striae, hirsutism, proximal muscle weakness, depression, and hyperglycemia. 1
Physical Manifestations
Body Composition Changes
- Central obesity with fat redistribution
- "Moon face" (rounded, plethoric facial appearance)
- Buffalo hump (dorsal fat pad)
- Supraclavicular fat pads
- Thin extremities contrasting with central obesity
Skin Changes
- Wide (1-cm) violaceous/purple striae, especially on abdomen
- Facial plethora (reddish-purple facial flushing)
- Easy bruising and ecchymoses
- Thin, fragile skin
- Hirsutism (excessive hair growth, particularly in women)
- Poor wound healing
Musculoskeletal Changes
- Proximal muscle weakness (difficulty climbing stairs, rising from chairs)
- Muscle wasting in extremities
- Osteopenia/osteoporosis (increased fracture risk)
Metabolic and Cardiovascular Manifestations
Metabolic Abnormalities
- Hyperglycemia or frank diabetes
- Hypertension (often resistant to treatment)
- Hypokalemia (particularly in ectopic ACTH or adrenal causes)
- Metabolic alkalosis
Cardiovascular Issues
- Increased risk of thromboembolism
- Arrhythmias (especially with hypokalemia)
- Edema and fluid retention
Neuropsychiatric Manifestations
- Depression
- Mood disorders
- Anxiety
- Sleep disturbances
- Cognitive impairment
- Memory problems
Reproductive Changes
- Menstrual irregularities in women
- Decreased libido
- Impotence in men
Growth and Development (in Children)
- Growth failure/short stature
- Weight gain
- Delayed puberty
Important Clinical Patterns to Recognize
In adults: The combination of central obesity, facial plethora, proximal muscle weakness, and wide purple striae is highly suggestive of Cushing's syndrome 1
In children: The combination of unexplained weight gain with either decreasing height SDS (standard deviation score) or decreased height velocity is particularly concerning for Cushing's syndrome 1
Screening Considerations
For patients presenting with suspicious features, screening tests include:
- Overnight 1-mg dexamethasone suppression test
- 24-hour urinary free cortisol excretion
- Late-night salivary cortisol 1
Pitfalls and Caveats
Diagnostic challenges: Many features of Cushing's syndrome (obesity, hypertension, glucose intolerance) are common in the general population, which can delay diagnosis until multiple features accumulate 2
Perioperative risks: Patients with Cushing's syndrome present significant anesthetic challenges including difficult ventilation/intubation, hemodynamic instability, and metabolic derangements 3, 4
Long-term consequences: Even after successful treatment, patients may experience persistent neurocognitive effects, psychiatric symptoms, and decreased quality of life 1
Mortality risk: Untreated Cushing's syndrome significantly increases mortality risk due to cardiovascular disease, infections, and thromboembolic events 2
Early recognition of this constellation of symptoms is crucial as prompt treatment can significantly reduce morbidity and mortality associated with chronic hypercortisolism.