Cushing’s Syndrome


Cushing’s syndrome (CS) is a constellation of features associated with prolonged exposure to inappropriately high levels of plasma glucocorticoids.

The most common cause of this is from exogenous glucocorticoid use.

Endogenous causes of Cushing’s syndrome are rare.

Classification & causes of Cushing’s Syndrome

1. ACTH-dependent

  1. Cushing’s disease
  2. Ectopic ACTH Syndrome
  3. Macronodular Adrenal Hyperplasia

2. ACTH-independent causes:

  1. Cortisol-secreting adrenal tumour
    or hyperplasia
  2. Iatrogenic Cushing’s Syndrome

Symptoms and Clinical features of Cushing’s Syndrome

  1. Weight gain, Moon facies, fat pads, truncal obesity;
  2. Facial plethora, red- purple striae
    ecchymoses, facial hair, hirsutism and male pattern balding in women, acne, Acanthosis nigricans, opportunistic fungal infections, poor wound healing.
  3. Ocular: Raised intraocular pressure,
    exophthalmos, Visual field defects
    Muscle weakness especially proximal myopathy
  4. Menstrual irregularities Рdecreased libido, decreased libido and impotence in men
  5. Lethargy, depression, emotional liability, psychosis, diabetes mellitus, loss of height, pathologic fractures, hypertension,
  6. Discriminatory features -reddish purple striae, plethora, proximal muscle weakness, bruising with no obvious trauma, and unexplained osteoporosis.


  • Serum electrolytes and glucose and FBC
  • Urine free cortisol (UFC; at least two measurements)
  • Late-night salivary cortisol (two measurements)
  • 1-mg overnight dexamethasone suppression test (DST)
  • Longer low-dose DST (2 mg/d for 48 h)

Determination of the cause of cushings

  • Morning plasma ACTH
  • High-Dose Dexamethasone Suppression Test
  • Inferior Petrosal Sinus Sampling and Selective Venous Catheterization-;
  • Imaging-CT/ MRI Scanning of Pituitary and Adrenals, scintigraphy

Differential diagnosis

  • Constitutional obesity
  • Other causes of weight gain
  • Pseudo cushings
  • Pregnancy
  • Depression
  • Bulimia
  • Alcoholism


  • Exclude causes of weight gain through history and examination
  • Confirm diagnosis and differential
    diagnoses before initiating treatment
  • Remove any underlying cause e.g. iatrogenic CS
  • General principal reduce level of plasma cortisol and treat any symptoms and complications
  • Surgical resection of the culprit tumour if patient qualifies.
  • Start with medical treatment and then surgery or continue medical treatment as indicated.

Medical Treatment

  1. Mifepristone,
  2. Adrenal steroid inhibitors
  3. Metyrapone
  4. Aminoglutethimide- commonly prescribed in combination with metyrapone.

Surgery: adrenalectomy or pituitary surgery

Radiotherapy: For failed surgery and/or patients not fit for surgery

Complications of Cushing’s Syndrome

  1. Diabetes mellitus
  2. Osteoprosis and fractures
  3. Hypopituitarism (compression of other gonadotrophs)
  4. Steroid psychosis

Complications Treatment

  1. Hormone replacement
  2. Lifelong glucocorticoid replacement with pituitary destruction or bilateral adrenalectomy.
  3. Lifelong mineralocorticoid replacement is also necessary in those patients who undergo
    bilateral adrenalectomy.


  • Favourable for adenomas if surgery is curative
  • CS due to carcinoma and adrenal
    hyperplasia have worse prognosis.

Leave a Comment