What are the signs and symptoms of Cushing syndrome in adults, particularly in women?

Cushing Syndrome Signs and Symptoms

Cushing syndrome presents with a characteristic constellation of physical findings including weight gain with central obesity, facial plethora, purple abdominal striae, easy bruising, proximal muscle weakness, and dorsocervical/supraclavicular fat pads ("buffalo hump"), along with metabolic derangements of hypertension and hyperglycemia that occur in over 80% of patients. 1, 2, 3

Cardinal Physical Signs

Cutaneous Manifestations

• Facial plethora (reddish, rounded face) is a characteristic finding 2, 3
• Purple striae (wide, >1 cm) particularly on the abdomen, distinguish Cushing syndrome from simple obesity 2, 3
• Easy bruising and skin fragility result from protein catabolism and collagen breakdown 1, 2
• Thin, fragile skin that tears easily 1, 3
• Acne, hirsutism, and alopecia are common dermatological features 4

Body Habitus Changes

• Central (truncal) obesity with fat redistribution to face, neck, and abdomen 2, 5
• Dorsocervical fat pad ("buffalo hump") 1, 3
• Supraclavicular fat accumulation 1, 3
• Weight gain despite normal or decreased appetite 1, 5

Musculoskeletal Features

• Proximal muscle weakness affecting hip and shoulder girdles, making it difficult to rise from a chair or climb stairs 1, 3
• Myopathy from protein catabolism 2, 4

Metabolic and Cardiovascular Manifestations

Highly Prevalent Complications

• Hypertension occurs in 70-90% of patients and has multifactorial pathogenesis including mineralocorticoid receptor activation and renin-angiotensin system stimulation 1, 4
• Glucose abnormalities exceed 80% prevalence, ranging from impaired glucose tolerance to frank diabetes mellitus 1, 4
• Dyslipidemia contributing to metabolic syndrome 4, 3

Gender-Specific Features in Women

Reproductive and Endocrine

• Menstrual irregularities including oligomenorrhea or amenorrhea 1, 3
• Hirsutism from androgen excess 1, 4
• Sexual dysfunction and decreased libido 4

Important caveat: In adult women, mood disorders and menstrual irregularities can overlap with perimenopause, potentially delaying diagnosis by an average of 3 years, which increases cardiovascular mortality risk 1

Neuropsychiatric Manifestations

• Mood disorders including depression, anxiety, and emotional lability 1, 2, 3
• Cognitive impairment and memory difficulties 4, 3
• Mania or psychosis in severe cases 4
• Increased suicide risk from psychiatric complications 4

Additional Clinical Features

Immunologic and Infectious

• Increased susceptibility to infections from immunosuppression 2, 4, 3
• Risk of opportunistic infections and sepsis 4, 3

Skeletal

• Osteoporosis and increased fracture risk from bone loss 4, 3

Ophthalmologic (when pituitary adenoma present)

• Visual field defects from mass effect on optic chiasm (cranial nerve II) 5
• Cranial nerve palsies (III, IV, VI) with macroadenomas 5

Critical Diagnostic Distinctions

A key discriminating feature in children and adolescents is growth failure with weight gain - height velocity decreases while BMI increases, which has high sensitivity and specificity for distinguishing Cushing syndrome from simple obesity 6

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 3

Common Diagnostic Pitfalls

• Excessive sweating is NOT a characteristic feature of Cushing syndrome, despite being commonly attributed to it 1
• Simple obesity typically shows proportional height and weight gain, whereas Cushing syndrome shows weight gain with growth deceleration in children 6
• Attributing symptoms to other common conditions (perimenopause, depression, metabolic syndrome) delays diagnosis and increases mortality from cardiovascular events 1, 3