What are the typical signs and symptoms of Cushing syndrome?

Clinical Manifestations of Cushing Syndrome

Cushing syndrome presents with a constellation of characteristic physical findings and metabolic abnormalities, with the most specific features being abnormal fat distribution in the supraclavicular and temporal fossae, wide purple striae (≥1 cm), proximal muscle weakness, and facial plethora. 1, 2, 3

Most Discriminating Physical Features

The following features have the highest specificity for distinguishing pathologic hypercortisolism from common conditions:

• Wide purple/violaceous striae (≥1 cm) on the abdomen, thighs, or arms are a cardinal feature that distinguishes Cushing syndrome from simple obesity or metabolic syndrome 1, 2, 4
• Proximal muscle weakness affecting hip flexors and shoulder girdle, causing difficulty rising from a chair or lifting objects overhead 1, 2, 3
• Abnormal fat distribution with supraclavicular fat pads, temporal fossa fullness, and dorsocervical fat pad (buffalo hump) 2, 4, 3
• Facial plethora (reddish-purple facial appearance) combined with moon facies (rounded facial appearance) 2, 4, 3

Additional Common Clinical Features

Dermatologic Manifestations

• Thin, fragile skin with easy bruising 1, 4, 5
• Facial acne 2
• Hirsutism in women (excessive hair growth in male-pattern distribution) 1, 2

Body Habitus Changes

• Central obesity with rapid weight gain over months rather than years 1, 4
• Visceral fat accumulation 4

Metabolic and Cardiovascular

• Hypertension occurs in 70-90% of patients, driven by mineralocorticoid receptor activation and multiple additional pathways including renin-angiotensin system activation 1, 2, 4
• Glucose abnormalities exceed 80% prevalence, ranging from impaired glucose tolerance to frank diabetes 1, 2
• Fluid retention 2

Neuropsychiatric

• Mood disorders, depression, and anxiety are common manifestations 1, 5
• Cognitive impairment and memory problems, particularly in children where ~25% experience long-term cognitive difficulties even after cure 6
• Behavioral symptoms 6

Reproductive

• Menstrual irregularities in females 6, 2

Musculoskeletal

• Muscle wasting, especially in lower limbs 2
• Decreased linear growth with continued weight gain in children (highly specific pediatric finding) 3

Critical Clinical Pitfalls

• Not all features are present in every patient, and the clinical presentation varies based on the extent and duration of cortisol excess 4, 7
• Many signs and symptoms (hypertension, weight gain, mood changes) are common in the general population, leading to an average diagnostic delay of 3 years from initial symptoms to diagnosis 1
• The absence of striae does not rule out Cushing syndrome—in children, the combination of unexplained obesity with decreased height velocity or decrement in height standard deviation score has high sensitivity and specificity without requiring striae 2
• The combination of central obesity, moon face, dorsocervical fat pad, and wide purple striae has high specificity when present together 2

Associated Severe Morbidities

• Increased mortality from pulmonary emboli, infections, myocardial infarction, and cerebrovascular accidents 5
• Thromboembolic disease risk 7
• Increased infection susceptibility due to immunosuppression 4, 5
• Cardiovascular disease 7
• Impaired quality of life that persists even 1 year post-treatment in children 6

Pediatric-Specific Considerations

• Cerebral atrophy occurs at diagnosis but reverses almost completely 1 year after surgical cure, though paradoxically cognitive function may decline initially 6
• Grey matter volume loss reverses 3 months after remission except in frontal and temporal lobes, which are strongly associated with cognition and memory 6
• Severe psychiatric and behavioral symptoms improve notably after cure, but long-term cognitive and memory problems persist in approximately 25% of patients 6