Symptoms of Cushing's Syndrome
Cushing's syndrome presents with a constellation of characteristic symptoms including central obesity, moon face, buffalo hump, purple striae, thin fragile skin, easy bruising, hypertension, glucose intolerance, muscle weakness, and neuropsychiatric disturbances. 1
Physical Manifestations
Body Composition Changes
- Central (visceral) obesity with relatively thin extremities
- Supraclavicular and dorsocervical fat pads ("buffalo hump")
- Moon face (rounded, plethoric facial appearance)
- Weight gain, particularly in the trunk
Skin Changes
- Purple/reddish striae (especially on abdomen, breasts, thighs)
- Thin, fragile skin that bruises easily
- Poor wound healing
- Facial plethora (reddened face)
- Acne
- Hirsutism (excessive hair growth, particularly in women)
Musculoskeletal Manifestations
- Proximal muscle weakness (difficulty rising from chairs, climbing stairs)
- Muscle atrophy
- Osteoporosis and pathological fractures
- Back pain due to vertebral compression fractures
Metabolic and Cardiovascular Manifestations
Cardiovascular
- Hypertension (present in >80% of patients) 1
- Increased cardiovascular risk
- Edema
Metabolic
- Glucose intolerance or diabetes mellitus
- Dyslipidemia
- Menstrual irregularities in women
- Decreased libido and fertility issues in both sexes
Neuropsychiatric Manifestations
- Mood disorders (depression, irritability, emotional lability)
- Cognitive impairment
- Insomnia
- Anxiety
- Psychosis (in severe cases)
Key Diagnostic Features
The most specific combination of symptoms for diagnosis includes 2:
- Unexplained weight gain with central obesity
- Proximal muscle weakness
- Wide (1-cm) violaceous striae
- Facial plethora
- Easy bruising
Special Considerations
In Children
Children with Cushing's syndrome typically present with:
- Growth failure (decreased height velocity)
- Weight gain
- Pubertal delay 2
In Pregnancy
Cushing's syndrome in pregnancy can be difficult to diagnose as some features (weight gain, striae) overlap with normal pregnancy changes.
Diagnostic Approach
When Cushing's syndrome is suspected based on clinical features, diagnostic testing should include 1, 3:
Screening tests:
- 24-hour urinary free cortisol (sensitivity >90%)
- Late-night salivary cortisol (sensitivity >90%, specificity 100%)
- 1-mg overnight dexamethasone suppression test
Confirmation tests to determine etiology:
- Plasma ACTH levels
- Imaging studies (pituitary MRI, adrenal CT)
Pitfalls to Avoid
- Don't dismiss mild presentations - not all patients have the full spectrum of symptoms
- Remember that obesity and metabolic syndrome can mimic some features of Cushing's syndrome
- Be aware that exogenous glucocorticoid use is the most common cause of Cushing's syndrome and should be ruled out first
- Recognize that the diagnosis is often delayed by 3-5 years from symptom onset, leading to increased morbidity and mortality 4
Early recognition of this constellation of symptoms is crucial as Cushing's syndrome is associated with significant morbidity and mortality if left untreated 1, 3.