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Cushings syndrome

– Clinical state of increased glucocorticoids

– Most commonly due to corticosteroids therapy/adrenocorticotropic hormone (ACTH)

Etiology

  • ACTH dependent
    • Pituitary dependent – Cushings disease (65% cases)
    • Synthetic ACTH
    • ACTH tumours
  • Non ACTH dependent
    • Adrenal adenoma/carcinoma
    • Complication of corticosteroid therapy
    • Alcohol induced pseudo-cushings

Clinical features

  • Pigmentation (ACTH only), hypokalemia, impaired glucose tolerance (frank diabetes), hypertension
  • Signs and symptoms

Diagnosis

  • Need to demonstrate inappropriate cortisol secretion – not supressed by exogenous steroids
  • Dexamethasone suppression test – normal people supress levels to <50nmol/l (low dose 48h)

Differential diagnosis

  • Plasma ACTH – <10nmol/l = non ACTH dependent
  • Adrenal CT/MRI
  • Serum potassium – hypokalemia (common ectopic ACTH secretion)
  • CRH (corticotrophin releasing hormone ) test/ high dose dexamethasone test
  • CXR – bronchial carcinoid

Treatment

  • If untreated death from hypertension, AMI, heart failure
  • Cortisol levels must be controlled before radiotherapy/surgery
    • Trans-sphenoidal surgery, pituitary irradiation, bilateral adrenal irradiation

Drugs

  • Metyrapone [1-4g/day q.i.d] (11B hydroxaylase inhibitor)
  • Ketoconazole – [200mg t.i.d] (imidazole derivative, 17 alpha hydroxylase inhibitor)
  • Decrease ACTH
    • Bromocriptine, cabergoline, somatostatin analogues
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