From the Guidelines
Cushing's syndrome is characterized by a constellation of features resulting from chronic excess cortisol exposure, including central obesity, moon face, facial plethora, purple striae, proximal muscle weakness, skin changes, metabolic disturbances, and psychological symptoms. The classic physical manifestations of Cushing's syndrome include central obesity with a "buffalo hump" (fat accumulation at the base of the neck), moon face, facial plethora, and purple striae on the abdomen 1. Patients often develop proximal muscle weakness, particularly in the lower limbs, making it difficult to climb stairs or rise from a seated position. Skin changes are prominent, including thinning, easy bruising, poor wound healing, and acne. Metabolic disturbances include glucose intolerance or frank diabetes mellitus, hypertension, and dyslipidemia 2.
Key Features
- Central obesity with a "buffalo hump"
- Moon face
- Facial plethora
- Purple striae on the abdomen
- Proximal muscle weakness
- Skin changes (thinning, easy bruising, poor wound healing, acne)
- Metabolic disturbances (glucose intolerance, diabetes mellitus, hypertension, dyslipidemia)
- Psychological symptoms (depression, irritability, anxiety, cognitive impairment)
- Menstrual irregularities and hirsutism in women
- Decreased libido and erectile dysfunction in men
- Growth retardation despite obesity in children These features develop because cortisol affects virtually every tissue in the body, altering metabolism, immune function, and protein synthesis 1. The severity of symptoms correlates with the degree and duration of hypercortisolism, with some features appearing early (facial plethora, weight gain) and others developing with prolonged exposure (striae, osteoporosis) 2.
From the Research
Clinical Features of Cushing's Syndrome
- Cushing's syndrome is characterized by a prolonged increase in plasma cortisol levels, leading to various clinical manifestations, including hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders 3.
- The syndrome is associated with skin changes, such as facial plethora, easy bruising, and purple striae, as well as metabolic manifestations like hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs 3.
- Cushing's disease, a form of Cushing's syndrome, is caused by a benign pituitary tumor producing excess corticotropin, and occurs in approximately 60% to 70% of patients with endogenous cortisol production 3.
Diagnosis of Cushing's Syndrome
- The diagnosis of Cushing's syndrome involves a stepwise process, including screening and confirming the diagnosis, as well as establishing the aetiology of the syndrome 4.
- Screening tests for Cushing's syndrome include 24-hour urinary free cortisol measurements, the dexamethasone suppression test, and late-night salivary cortisol or midnight serum cortisol measurements 4.
- Late-night salivary cortisol measurement is a simple and reliable screening test for spontaneous Cushing's syndrome, with a sensitivity of 92% 5.
Aetiology and Treatment of Cushing's Syndrome
- The aetiology of Cushing's syndrome can be established through measurement of ACTH, adrenal imaging, and other tests, such as pituitary MRI imaging and bilateral inferior petrosal sinus sampling 3, 4.
- The first-line therapy for endogenous Cushing's syndrome is surgical resection of the causal tissue, followed by medication, including adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers 3, 6.
- Radiation therapy and bilateral adrenalectomy may be considered for patients who are not responsive to surgery and medication 3, 6.