Clinical Signs that Prompt Suspicion of Cushing's Disease
The most important clinical signs that should prompt a provider to suspect Cushing's disease are central obesity, "moon" face, dorsal and supraclavicular fat pads, wide violaceous striae, hirsutism, and proximal muscle weakness. 1
Cardinal Clinical Manifestations
Physical Appearance Changes
- Central obesity - disproportionate fat accumulation in trunk with relatively thin extremities
- "Moon face" - rounded, plethoric facial appearance
- Buffalo hump - dorsal fat pad between shoulders
- Supraclavicular fat pads - fat accumulation above the clavicles
- Wide violaceous striae (>1 cm) - especially on abdomen, breasts, thighs
- Facial plethora - reddish-purple facial coloration
Skin and Soft Tissue Changes
- Hirsutism - excessive hair growth in women in male-pattern distribution
- Easy bruising - due to skin fragility
- Thin, fragile skin - paper-like appearance
- Poor wound healing
- Acne
Musculoskeletal Changes
- Proximal muscle weakness - difficulty rising from sitting position or climbing stairs
- Osteoporosis - may present with fractures
Metabolic and Cardiovascular Manifestations
- Hypertension - often resistant to treatment 2
- Hyperglycemia/diabetes - due to insulin resistance 1
- Weight gain - especially central
Neuropsychiatric Manifestations
- Depression - common mood disturbance 1
- Cognitive changes - memory problems, difficulty concentrating
- Sleep disturbances
Reproductive Changes
- Menstrual irregularities in women
- Decreased libido
- Erectile dysfunction in men
Epidemiology and Prevalence
Cushing's disease is rare, with a prevalence of less than 0.1% in the general population 2, 1. However, it's important to consider this diagnosis in patients with the characteristic constellation of symptoms, as early diagnosis improves outcomes.
Diagnostic Approach
When these clinical signs raise suspicion for Cushing's disease, the American Heart Association recommends screening with:
- Overnight 1-mg dexamethasone suppression test
- 24-hour urinary free cortisol excretion (preferably multiple samples)
- Midnight salivary cortisol 2, 1
Important Considerations
- Exogenous glucocorticoid use must be excluded before biochemical testing 1
- Metabolic syndrome can mimic some features of Cushing's syndrome 1
- The diagnosis is often delayed by an average of 3 years due to the gradual onset of symptoms 3
- Consider Cushing's disease particularly when multiple characteristic features are present together, as individual symptoms like hypertension or weight gain alone are common in the general population and don't justify testing 3
Early recognition of this constellation of signs is crucial as Cushing's disease is associated with significant morbidity and mortality if left untreated, including cardiovascular complications, infections, and osteoporotic fractures.