Adrenal Insufficiency

Review of the Physiology

  • Hypothalmus
    • CRH –> pituitary ACTH –>  adrenals to make glucocorticoids, mineralcorticoids and androgens
  • Adrenal Gland
    • Cortex makes cortisol, adrenal androgens and aldosterone
      • Glomerulosa (aldosterone – salt)
      • Fasciculata (cortisol – sugar)
      • Reticularis (androgens – sex)
    • Medulla makes epinephrine




  • Primary
    • Autoimmune (Addison’s disease)
    • Polyglandular syndromes
    • Granulomatous infections (sarcoid, fungal infections, etc)
    • Infiltrative diseases (HIV, CMV, amyloid)
    • High ACTH
    • Hemorrhage
  • Secondary
    • Rapid withdrawal of exogenous steroids
    • Low or inappropriately normal ACTH

Signs and Symptoms

Acute adrenal insufficiency/adrenal crisis  can be an endocrine emergency!

  • All causes: weakness, weight loss, NV, fatigue, vague abd pain, hypercalcemia (20%)
  • Primary: hypotension and hyperpigmentation, hyperkalemia and hyponatremia (due to affecting both the aldo and cortisol)
  • Secondary: hypotension but not associated with hyperkalemia (because aldo is still released by the renin-angiotension response)


  • If acute AI suspected with s/sx of shock, must give steroids right away – Dexamethasone will not interfere with cortisol test but will affect ACTH.
  • If stable, check Cosyntropin stim test
    • Check baseline cortisol
    • Give 0.25 mg cosyntropin
    • Recheck cortisol at 30 and 60 mins
    • Expected stimulation >18-20
    • Check ACTH
    • Check aldo level
    • Expected findings:
      • Primary
        • Low stim test
        • High ACTH
        • Low aldo
      • Secondary or tertiary
        • Low stim test
        • Low or normal ACTH
        • Normal aldo


  • Acute adrenal insufficiency (ADRENAL CRISIS!)
    • General idea: this is a medical emergency! High fatality rate if not treated (approaching 100%). If adrenal crisis is suspected, start treatment before labs have resulted!
    • IV Fluids: 2-3 L NS or d5NS bolus as quickly as possible to correct hypotension and hyponatremia. Continue IVF for the next 24-48 hours or until stabilization.
    • Glucocorticoids:
      • Dexamethasone: use if cosyntropin stim test has NOT been performed, as it does not interfere with the measurement of plasma cortisol. Give 4 mg decadron IV q12h.
      • Hydrocortisone: use if the diagnosis has already been made or decadron is not available. Give 100mg q6h for 2-3 days.
      • Continue IV steroids for 2-3 days or until stabilization – then taper to PO hydrocortisone.
    • Mineralcorticoids:
      • Needed only in primary adrenal insuffi ciency
      • Not needed if hydrocortisone dose >50 mg per 24 h, as this will activate the mineralcorticoid receptor
  • Chronic adrenal insufficiency:
    • Glucocorticoid: hydrocortisone split into 2-3 doses daily, with 2/3 in the AM and 1/3 in the PM. Aim for the lowest possible steroid dose to relieve signs and symptoms.
      • Primary adrenal insufficiency: start on 20–25 mg hydrocortisone per 24 h
      • Secondary adrenal insufficiency: 15–20 mg hydrocortisone per 24 h
      • Increase to stress dose for acute illnesses
    • Mineralcorticoid: Needed only in primary adrenal insufficiency, and not if total hydrocortisone dose is greater than 50mg/day.
      • Fludrocortisone oral 0.05-0.1 mg/day (lower dose may be sufficient in patients receiving hydrocortisone).
    • Sex Steroids: consider in patients who complain of decreased energy, sexual dysfunction, or impaired mood despite optimum replacement therapy with glucocorticoids and mineralocorticoids.
      • Start with DHEA 25–50 mg as a single morning dose



  • Charmandari, Evangelia et al. Adrenal insufficiency. The Lancet , Volume 383 , Issue 9935, 2152 – 2167.
  • Arlt, Wiebke et al. Adrenal insufficiency. The Lancet , Volume 361, Issue 9372 , 1881 – 1893.
  • Jadoul, et al. Mineralocorticoids in the management of primary adrenocortical insufficiency. Journal of Endocrinological Investigation. February 1991, Volume 14, Issue 2, pp 87-91.
  • Arlt, Wiebke et al. The Approach to the Adult with Newly Diagnosed Adrenal Insufficiency. The Journal of Clinical Endocrinology & Metabolism 2009 94:4, 1059-1067