- Cushing’s disease: increased secretion of adrenocorticotropic hormone (ACTH) causing Cushing’s syndrome
- Cushing’s syndrome: collection of signs and symptoms resulting from increased cortisol
Clinical manifestations
- Symptoms
- Poor vision (cataracts)
- Progressive obesity
- Easy bruising
- Hyperpigmentation (ACTH excess only)
- Acne
- Increase in bodily hair (especially females) / virilization
- Difficulty in climbing stairs (proximal myopathy)
- Hip pain (avascular necrosis of the femoral head)
- Fragility fractures
- Worsening diabetic control
- Worsening hypertensive control
- Signs
- Centripetal obesity
- Cataracts
- Acne vulgaris
- Hirsutism
- Thin skin
- Poor wound healing
- Easy bruising
- Acanthosis nigricans
- Proximal myopathy
- Violaceous striae over the abdomen
- Prominent Interscapular fat pad
Differential diagnosis
- Drug-induced
- Glucocorticoids for immunosuppression
- High-dose inhaled corticosteroids for asthma
- Traditional Chinese medicines
- Adrenal tumours
- Cushing’s disease
- ACTH-secreting pituitary adenoma
- Ectopic ACTH secretion
- Small cell lung cancer
- Carcinoid tumour
- Carcinoma of the pancreas
Investigations
- Confirm diagnosis
- Midnight serum cortisol for screening (cortisol nadir occurs at midnight)
- 24-hour urinary free cortisol (high, usually 3x upper limit of normal)
- Overnight dexamethasone suppression test (failure to suppress)
- Inferior petrosal sinus sampling to determine if there is a pituitary source
- Magnetic resonance imaging of the brain to look for pituitary adenoma
- Computed tomography scan of the abdomen with adrenal cuts to look for adrenal adenoma
- DEXA scan to look for osteoporosis
Management
- Multidisciplinary team approach
- Patient education
- Withdrawal of offending drug – stop TCM slowly
- Surgery (definitive)
- Trans-sphenoidal hypophysectomy for pituitary adenoma
- Adrenalectomy for adrenal adenoma
- Medical
- Ketoconazole if surgery unsuccessful or while awaiting surgery
- Metyrapone (second-line)
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