Cushing’s syndrome

Cushing’s syndrome

  • Can be caused by exogenous admin, over production of ACTH by the pituitary gland causes adrenal hyperplasia
  • Can be caused by excessive ACHT production resulting from a tumor (usually in the pancreas, thyroid or lung)
  • May be either ACTH-dependent or ACTH-independent
  • S/S:  buffalo hump & supraclavicular fat pads, stretch lines on the stomach
  • Survival is 4-5 years following diagnosis w/o treatment
  • Surgery is first line therapy
    • 4 categories of drug therapy:  steroidogenic inhibitors, adrenolytic agents, neuromodulators of ACTH release, glucocorticoid receptor blocking agents
      • Steroidogenic inhibitors:  inhibit cortisol synthesis through enzymatic inhibition
        • Metyrapone can increase ACTh initially (thus resulting in increased androgenic & mineralocorticoid hormones–HTN, acne, hirsutism)
        • Aminoglutethimide:  reduces plasma cortisol by 50%  (SE:  dose related sedation, nausea, rash)
        • Ketoconazole:  results in normal cortisol for 84% of cushing’s patients  (SE:  elevated LFTs, gynecomastia, Gi upset)
        • IV Etomidate:  sedative hypnotic used for hypercortisolemia (prior to surgery)
      • Adenolytic agents
        • Mitotane inhibits enzymes in the adrenal cortex resulting in eventual atrophy of the adrenal cortex
          • Steroid replacement may be needed
          • Common SE:  lethargy, somnolence, hypercholesterolemia
      • Neuromodulatory agents reduce ACTH but efficacy is questionable
        • Ex.  Cyproheptadine, bromocriptine, valproate, rosiglitazone, etc
      • Glucocorticoid receptor blocker (ex.  RU-486, mifepristone) antagonize progesterone & glucocorticoid receptors but their efficacy is questionable
        • Spironolactone is an aldosterone antagonist that is used to treat HTN & hypokalemia in Cushing’s syndrome
          • Need to monitor cortisol to avoid adrenal insufficiency

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