What are the clinical features of Cushing syndrome?

Clinical Features of Cushing Syndrome

Cushing syndrome presents with a constellation of physical findings dominated by central obesity, facial plethora, wide purple striae (≥1 cm), easy bruising, and proximal muscle weakness—features that occur in over 80% of patients and distinguish pathologic hypercortisolism from simple obesity or metabolic syndrome. 1

Cardinal Physical Manifestations

Cutaneous Features

• Facial plethora (reddish, rounded face) is a hallmark sign present in the majority of patients 1, 2
• Wide purple/violaceous striae (≥1 cm width) on the abdomen, thighs, or arms are highly specific for Cushing syndrome and distinguish it from simple obesity 1, 3
• Easy bruising and skin fragility result from protein catabolism and collagen breakdown, causing skin that tears easily 1
• Thin, fragile skin is characteristic and reflects the catabolic effects of excess cortisol 1
• Hirsutism from androgen excess occurs commonly in women 1, 3

Body Habitus Changes

• Central obesity with weight gain despite normal or decreased appetite is a key feature 1
• Dorsocervical fat pad ("buffalo hump") and supraclavicular fat accumulation are pathognomonic 1, 2
• Fat redistribution to face, back of neck, and visceral organs creates the characteristic appearance 2

Musculoskeletal Features

• Proximal muscle weakness affecting hip flexors and shoulder girdles causes difficulty rising from a chair or lifting objects overhead 1, 3
• This weakness is a critical discriminator from simple obesity 3
• Osteoporosis and skeletal fractures occur due to cortisol's effects on bone 4

Metabolic and Cardiovascular Manifestations

Glucose Abnormalities

• Glucose abnormalities exceed 80% prevalence, ranging from impaired glucose tolerance to frank diabetes mellitus 1, 3
• Hyperglycemia results from cortisol's effects on glucose metabolism 2, 4

Hypertension

• Hypertension occurs in 70-90% of patients with multifactorial pathogenesis 1, 3
• Mechanisms include mineralocorticoid receptor activation by excess cortisol, increased renal sodium absorption, renin-angiotensin system activation, and sensitization of vasculature to catecholamines 3
• Hypertension contributes to increased risk for myocardial infarction, cardiac failure, and stroke 4

Gender-Specific Features

Women

• Menstrual irregularities including oligomenorrhea or amenorrhea are common 1
• Hirsutism from androgen excess is characteristic 1

Men

• Hypogonadism may develop, particularly with certain medical therapies 5

Neuropsychiatric Manifestations

• Major depression is the most common psychiatric comorbidity 6
• Mood disorders, anxiety, and cognitive dysfunction occur frequently 1, 2, 4
• Mania can occur in some patients 4, 6
• These psychiatric features can be responsible for suicide 4

Critical Diagnostic Distinctions

In Children and Adolescents

• Growth failure with weight gain has high sensitivity and specificity for distinguishing Cushing syndrome from simple obesity 1
• Decreased linear growth with continued weight gain is highly specific 7

In Adults

• The combination of multiple features is more diagnostic than any single finding, as isolated symptoms like weight gain or mood changes are common in the general population 1
• Rapid weight gain over months rather than years, particularly with central distribution, warrants screening 3

Important Diagnostic Pitfalls

Features NOT Characteristic of Cushing Syndrome

• Excessive sweating is NOT a characteristic feature despite being commonly attributed to it 3

Common Misattributions That Delay Diagnosis

• Attributing symptoms to perimenopause, depression, or metabolic syndrome delays diagnosis and increases mortality from cardiovascular events 1
• The average diagnostic delay is 3 years from initial symptoms to diagnosis 3
• Simple obesity shows proportional height and weight gain, whereas Cushing syndrome shows weight gain with growth deceleration in children 1

Additional Clinical Complications

Prothrombotic State

• Hypercoagulability paradoxically coexists with increased bleeding tendency from capillary fragility 5
• Venous thromboembolic events occur at 10-fold higher rates than in healthy populations 5

Immunologic Effects

• Immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis (an important cause of death) 4
• Immune rebound after disease remission can exacerbate underlying autoimmune diseases 4

Dermatologic Manifestations

• Acne, hirsutism, and alopecia are common dermatological features 4

Clinical Presentation Variability

The clinical features are variable, and no single pattern is seen in all patients 7. However, abnormal fat distribution (particularly in supraclavicular and temporal fossae), proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in children are the most specific features 7.