What are the cardinal features of Cushing's syndrome?

Cardinal Features of Cushing's Syndrome

Cushing's syndrome is characterized by central obesity, "moon" face, dorsal and supraclavicular fat pads, wide (1-cm) violaceous striae, hirsutism, and proximal muscle weakness, which are the cardinal clinical manifestations of chronic hypercortisolism. 1

Physical Manifestations

Body Composition Changes

• Central obesity: Rapid weight gain with preferential fat deposition in the abdomen 2
• "Moon face": Rounded, plethoric facial appearance 1, 2
• Buffalo hump: Fat accumulation in the dorsocervical area 2, 3
• Supraclavicular fat pads: Fat deposits above the clavicles 1, 2

Skin Changes

• Wide violaceous striae (1-cm): Purple-red stretch marks, particularly on the abdomen 1, 2
• Facial plethora: Reddish-purple facial flushing 4
• Easy bruising: Due to skin thinning and capillary fragility 4
• Hirsutism: Excessive hair growth, particularly in women 1
• Acne: Common dermatological manifestation 5

Musculoskeletal Features

• Proximal muscle weakness: Particularly affecting the shoulders and hips 1, 2
• Osteopenia/osteoporosis: Leading to increased fracture risk 5

Metabolic and Cardiovascular Manifestations

• Hypertension: Present in most cases, often resistant to treatment 1
• Hyperglycemia/diabetes: Due to insulin resistance 1, 4
• Dyslipidemia: Contributing to cardiovascular risk 5

Neuropsychiatric Features

• Depression: Common mood disturbance 1, 4
• Cognitive impairment: Memory and concentration difficulties 5
• Mood disorders: Including irritability and emotional lability 4, 6

Reproductive and Sexual Dysfunction

• Menstrual irregularities: Including amenorrhea in women 3
• Decreased libido: In both men and women 5

Laboratory Findings

• Hypokalemia: Particularly with ectopic ACTH production 1
• Metabolic alkalosis: Due to mineralocorticoid effects of excess cortisol 1

Diagnostic Approach

The American Heart Association recommends screening for Cushing's syndrome using:

1. Overnight 1-mg dexamethasone suppression test 1, 2
2. 24-hour urinary free cortisol excretion (preferably multiple samples) 1, 2
3. Midnight salivary cortisol 2, 4

Clinical Pitfalls and Caveats

• The prevalence of Cushing's syndrome is less than 0.1% in the general population, making it a rare but important cause of central obesity 1
• Metabolic syndrome can mimic some features of Cushing's syndrome 2
• Pseudo-Cushing's syndrome can present with biochemical hypercortisolism without full clinical manifestations 2
• Exogenous glucocorticoid use must be excluded before biochemical testing 1
• The clinical presentation may vary significantly between patients, with some showing only a subset of the classic features 4

Early recognition of these cardinal features is crucial as Cushing's syndrome is associated with increased mortality, primarily due to cardiovascular disease, infections, and thrombotic events if left untreated 5.