What are the signs and symptoms of Cushing's syndrome?

Signs and Symptoms of Cushing's Syndrome

Cushing's syndrome presents with a constellation of clinical features resulting from chronic glucocorticoid excess, with the most specific findings being abnormal fat distribution (supraclavicular and temporal fossae), proximal muscle weakness, wide purple striae, and in children, decreased linear growth with continued weight gain. 1, 2

Most Specific Clinical Features

The following signs are most discriminatory for Cushing's syndrome and should raise immediate clinical suspicion:

• Abnormal fat distribution in the supraclavicular fossae, temporal fossae, dorsal fat pad ("buffalo hump"), and facial plethora 1, 2
• Proximal muscle weakness affecting hip and shoulder girdles 2, 3
• Wide purple striae (>1 cm) on the abdomen, thighs, or arms 4, 2
• Easy bruising and fragile, thin skin 1, 4
• In children specifically: decreased linear growth velocity with continued weight gain 2

Common but Less Specific Manifestations

Metabolic and Cardiovascular

• Hypertension occurs in 70-90% of patients, driven by mineralocorticoid receptor activation and multiple pathways including renin-angiotensin system activation 5, 1
• Hyperglycemia and glucose abnormalities exceed 80% prevalence, mimicking severe metabolic syndrome 1, 4
• Central obesity with visceral fat accumulation 4, 3
• Dyslipidemia contributing to cardiovascular risk 5

Dermatologic

• Facial plethora (reddish appearance) 4, 3
• Hirsutism in women 1, 6
• Acne 6

Musculoskeletal

• Osteoporosis and vertebral fractures from protein catabolism 5, 4
• Generalized muscle weakness 1

Neuropsychiatric

• Mood disorders including depression and anxiety 1, 4
• Cognitive deficits 6
• Psychiatric disturbances 7, 3

Reproductive

• Menstrual irregularities in women 1, 6
• Decreased libido 6

Immunologic

• Increased susceptibility to infections due to immunosuppression 4, 3

Clinical Pitfalls and Caveats

A critical caveat is that no single pattern of symptoms occurs in all patients, and the clinical presentation varies based on the extent and duration of cortisol excess. 2, 6

• Many features (hypertension, weight gain, mood changes) are common in the general population, which can delay diagnosis 3, 6
• When hypercortisolism is severe, signs are unmistakable, but mild cases may present subtly 6
• The diagnosis should be considered when multiple features accumulate over time rather than waiting for all classic signs 3

Associated Severe Complications

• Thromboembolic disease including pulmonary emboli 3, 6
• Cardiovascular events (myocardial infarction, cerebrovascular accidents) are leading causes of increased mortality 7, 3
• Severe infections contributing to mortality risk 3

When to Screen

Screening should be initiated when patients present with multiple features of glucocorticoid excess, particularly when the most specific signs (supraclavicular fat, proximal weakness, wide purple striae) are present, using 24-hour urinary free cortisol, late-night salivary cortisol, or 1 mg dexamethasone suppression test. 8, 4, 3