What are the clinical manifestations of Cushing's (Cushing's) syndrome?

Clinical Manifestations of Cushing's Syndrome

Cushing's syndrome presents with a characteristic constellation of physical findings dominated by abnormal fat distribution (central obesity, moon face, buffalo hump), skin changes (purple striae, facial plethora, easy bruising), and proximal muscle weakness, alongside metabolic derangements including hypertension and hyperglycemia. 1, 2

Most Specific Physical Findings

The following features have the highest specificity for distinguishing Cushing's syndrome from common conditions:

• Abnormal fat distribution in the supraclavicular and temporal fossae—these locations are particularly diagnostic 1, 3
• Proximal muscle weakness manifesting as difficulty rising from a chair or climbing stairs 1, 4, 3
• Wide purple striae (violaceous stretch marks >1 cm) on the abdomen, thighs, or breasts 4, 5
• Stunted linear growth with continued weight gain in children—this combination is highly specific 1, 3

Common Physical Manifestations

Facial and Body Habitus Changes

• Moon face (rounded, full facial appearance) 1, 4, 6
• Buffalo hump (dorsocervical fat pad accumulation) 1, 4
• Central/truncal obesity with thin extremities (centripetal fat distribution) 1, 4, 2
• Facial plethora (reddish facial appearance) 7, 2, 5

Skin and Integumentary Changes

• Easy bruising and skin fragility 4, 2
• Acne 7, 4
• Skin hyperpigmentation (more prominent with ectopic ACTH production) 7

Metabolic and Systemic Manifestations

Cardiovascular and Metabolic

• Hypertension present in >80% of cases 7, 4, 2
• Hyperglycemia and glucose intolerance present in >80% of cases 4, 2
• Metabolic alkalosis with hypokalemia (particularly with ectopic ACTH) 7, 4
• Weight gain (though paradoxically, weight loss occurs in ~10% of cases associated with malignancy, particularly SCLC) 7, 4
• Peripheral edema 7, 4

Reproductive and Endocrine

• Menstrual irregularities and amenorrhea 7, 1
• Hirsutism 7, 6

Neuropsychiatric Manifestations

• Mood disorders including depression and anxiety 7, 4, 2
• Irritability, personality changes, and fussiness (up to 29% of patients) 4
• Insomnia 4
• Neurocognitive changes 2

Critical Diagnostic Pitfall

Before pursuing any biochemical testing, you must exclude iatrogenic Cushing's syndrome through detailed medication history—failure to do so leads to unnecessary testing and potential harm without patient benefit. 7, 4 This is based on high-quality evidence from the Endocrine Society. 7, 4

Routes of Exogenous Glucocorticoid Exposure to Assess:

• Oral, intravenous, or intramuscular corticosteroids 4
• High-potency topical skin corticosteroids 4
• Inhaled corticosteroids, especially when combined with CYP3A4 inhibitors like itraconazole 4
• Intralesional corticosteroid injections 4

Clinical Context and Prevalence

While Cushing's syndrome has a prevalence of <0.1% in the general population, studies demonstrate significantly higher prevalence among patients with diabetes, obesity, hypertension, and osteoporosis. 1, 5 The constellation of classic findings creates high specificity when multiple features are present together. 1

The clinical presentation is highly variable, and because individual features are common in the general population, diagnosis is often delayed until multiple characteristic features have accumulated. 8, 5 The average delay in diagnosis is approximately 3 years for some forms. 7