Symptoms of Hypercortisolism
Hypercortisolism (Cushing's syndrome) presents with a constellation of symptoms including weight gain with central obesity, proximal muscle weakness, hypertension, psychiatric disturbances, hirsutism, purple striae, buffalo hump, supraclavicular fat pad enlargement, hyperglycemia, and hypokalemia. 1
Clinical Presentation
Physical Manifestations
- Central obesity - characteristic fat distribution in trunk, face, and neck
- Facial changes:
- Moon face
- Facial plethora (redness)
- Supraclavicular fat pads
- Dorsocervical fat pad ("buffalo hump")
- Skin changes:
- Wide (>1 cm), purple striae
- Thin, fragile skin
- Easy bruising and ecchymoses
- Delayed wound healing
- Acne
- Musculoskeletal:
- Proximal muscle weakness (especially in thighs)
- Muscle atrophy
- Osteoporosis and increased fracture risk
Metabolic and Cardiovascular
- Hypertension (often severe and resistant to treatment)
- Hyperglycemia or diabetes mellitus
- Hypokalemia (especially with ectopic ACTH syndrome)
- Dyslipidemia
- Increased risk of cardiovascular events
Reproductive and Hormonal
- In women:
- Hirsutism
- Menstrual irregularities
- Decreased libido
- Infertility
- In men:
- Decreased libido
- Erectile dysfunction
Neuropsychiatric
- Depression
- Anxiety
- Irritability
- Sleep disturbances
- Cognitive impairment
- Psychosis (in severe cases)
Severity Indicators
Severe hypercortisolism is a medical emergency characterized by 2, 3:
- Markedly elevated cortisol levels
- Multiorgan failure
- Severe hypokalemia
- Uncontrolled hypertension
- Opportunistic infections
- Psychosis
- Thromboembolism
Diagnostic Considerations
When hypercortisolism is suspected based on clinical features, screening should include 1:
- 1 mg overnight dexamethasone suppression test (DST)
- Serum cortisol >50 nmol/L excludes cortisol hypersecretion
- 51-138 nmol/L suggests possible autonomous cortisol secretion
138 nmol/L indicates cortisol hypersecretion
- 24-hour urinary free cortisol
- Late-night salivary cortisol
- Plasma ACTH to determine if the hypercortisolism is ACTH-dependent or independent
Clinical Pitfalls
- Hypercortisolism must be considered in the differential diagnosis of common problems like hirsutism, menstrual irregularity, hypertension, diabetes mellitus, and obesity 4
- Older adults may present with more subtle symptoms, sometimes limited to cardiovascular manifestations ("apathetic hypercortisolism")
- Diagnostic difficulties may arise from drug interference, alcohol ingestion, and depression 4
- Subclinical hypercortisolism may still cause significant adverse effects, including increased mortality risk 5
Early recognition and treatment of hypercortisolism are crucial to prevent progressive complications including adiposity, myopathy, dermopathy, psychopathy, glucose intolerance, hypercholesterolemia, hypertension, atherosclerosis, immunosuppression, and ultimately death 6.