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Updated: Mar 18 2020

Addison Disease


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Images pigmentation.jpg
  • Snapshot
    • A 25-year-old man presents to the clinic for an annual check-up. He is otherwise healthy and has no significant concerns. Basic laboratory studies demonstrate a sodium level of 129 mg/dL and potassium level of 5.9 mg/dL. A physical examination demonstrates hyperpigmentation of the oral mucosa. Review of systems were positive for generalized fatigue, 5-lbs unintentional weight loss, and some headaches.
  • Introduction
    • Clinical definition
      • disorder characterized by the loss of adrenal gland function leading to the deficiency of glucocorticoids, mineralocorticoids, and adrenal androgens
      • can be either acute or chronic depending of the etiology
    • Epidemiology
      • demographics
        • autoimmune causes (which accounts for 70-90% of cases in the U.S.) occur predominantly within the female population
      • risk factors
        • other autoimmune endocrinopathies
    • Pathogenesis
      • any process that damages the adrenal cortices and leads to a deficiency of aldosterone, catecholamines, and cortisol
      • autoimmune adrenalitis (Addison disease)
        • most common cause in the U.S.
        • both humoral and cell-mediated immune mechanisms against the adrenal cortex
        • a small percentage of patients may have polyglandular autoimmune syndrome
      • infectious adrenalitis
        • tuberculosis (most common cause in the developing world)
        • disseminated fungal infections (e.g., histoplasmosis)
        • HIV infection
      • hemorrhagic infarction
        • Waterhouse-Friderichsen syndrome associated with meningococcemia (Neisseria meningitidis)
        • anticoagulant drug or heparin therapy (e.g., heparin-induced thrombocytopenia)
      • metastatic disease
        • commonly associated with lung, breast, and melanoma cancers
    • Associated conditions
      • approximately 1/2 of patients with autoimmune adrenal insufficiency have other autoimmune endocrine disorders (e.g., hypothyroidism)
  • Presentation
    • Symptoms
      • fatigue
      • weight loss
      • nausea/vomiting
      • abdominal pain
      • muscle/joint pain
      • salt craving
      • adrenal crisis
    • Physical exam
      • skin and mucosal hyperpigmentation (if longstanding)
        • due to increased production of proopiomelanocortin (POMC), a prohormone that is cleaved into ACTH and melanocyte-stimulating hormone (MSH)
      • hypotension
      • auricular-cartilage calcification
      • vitiligo
  • Imaging
    • Computed tomography (CT)
      • may demonstrate bilateral adrenal injury, hemorrhage, or infarction
  • Studies
    • Serum cortisol concentration (e.g., morning serum cortisol)
      • best initial test
      • low serum cortisol (e.g., < 5 ug/dL) strongly suggests adrenal insufficiency
    • Plasma ACTH concentration
      • best initial test but often not quickly available
      • high plasma ACTH concentration with low serum cortisol suggests primary adrenal insufficiency
    • ACTH stimulation test
      • will have low response to ACTH stimulation
    • Plasma aldosterone and renin levels
      • will have low aldosterone and high renin levels
    • Chemistry panel
      • hyperkalemia
      • hyponatremia
  • Differential
    • Secondary adrenal insufficiency
      • distinguishing factors
        • will not have hyperpigmentation on physical examination
        • will have low levels of ACTH
  • Treatment
    • Glucocorticoid replacement therapy
      • e.g., hydrocortisone or dexamethasone
      • stress doses indicated at times of stress (e.g., surgery)
      • significant adverse effects with chronic use (e.g., osteoporosis)
    • Mineralcorticoid replacement therapy
      • e.g., fludrocortisone
      • prevents sodium loss, intravascular volume depletion, and hyperkalemia
    • Androgen replacement therapy
      • e.g., dehydroepiandrosterone (DHEA)
      • appears to improve mood and psychological well-being
      • adverse effects include hirsutism, acne, and increased sweating/odor
  • Complications
    • Adrenal crisis
      • medical emergency managed with schedule IV glucocorticoid
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