Medical Pharmacology Chapter 28:  Physiology and Pharmacology: Adrenocorticosteroids / Adrenocortical Antagonists

• Treatment of Primary Adrenocortical Deficiency (Addison's Disease)

  • Replacement Therapy

    • Correction of both glucocorticoid and mineralocorticoid deficiency

    • Therapeutic Mainstay:  Cortisol

      • Treatment complications: rare; except for gastritis

    • Mineralocorticoid component:  fludrocortisone

      • Adequacy assessed by serum electrolyte and blood pressure measurements

      • Blood pressure: normal; no orthostatic effects

      • Serum sodium, potassium, creatinine, blood urea nitrogen levels: normal

      •  Treatment complications:

        1. Hypokalemia

        2. Hypertension

        3. Cardiac enlargement

        4. Congestive heart failure (secondary to sodium retention)

  •  Special considerations:

    • During illness (especially if fever is present): hydrocortisone dosage should be increased (doubled)

    • Supplemental glucocorticoid dosage before:

      • Surgery

      • Dental extraction

    • Supplemental fludrocortisone plus salt upon:

      • Strenuous exercise with sweating during very hot weather

      • Gastrointestinal upsets

• Acute Adrenocortical Insufficiency

  • May occur are due to:

    1.  Rapid intensification of chronic adrenal insufficiency

       • Precipitated by sepsis or surgical stress

    2.  Acute hemorrhagic adrenal gland destruction in a previously healthy individual

       •  In children: associated with Pseudomonas septicemia or meningiococcemia

       •  In adults: associated with anticoagulant treatment/coagulation disorder

    3. Most frequent cause of acute adrenal insufficiency:

       • Rapid withdrawal of steroids from patients who have adrenal atrophy following prolonged chronic steroid administration

    4. Other causes:

       • Patients with congenital adrenal hyperplasia or with decreased adrenocortical reserve when:

         • They are given drugs that inhibit steroid synthesis, e.g. mitotane (Lysodren), ketoconazole (Nizoral) or

         • They are given drugs that increase steroid metabolism, e.g. phenytoin (Dilantin), rifampin (Rimactane)

  • Prognosis

    • Long-term survival: dependent on prevention and proper treatment of adrenal crisis:

    • Prevention of crisis: infection, trauma, gastrointestinal upsets, other stresses: require immediate increase in administered hormone. Otherwise, symptoms may intensify.

      • Nausea

      • Vomiting

      • Abdominal pain

      • Lethargy, somnolence

      • Hypovolemic vascular collapse

    • Treatment: based on replacing glucocorticoids and sodium/water deficits

      • Intravenous 5% glucose infusion (in normal saline)

      • Initiated with IV bolus of 100 mg hydrocortisone, followed by continuous hydrocortisone (Cortef, Solu-Cortef) infusion (10 mg/h)

      • Management of hypotension requires glucocorticoid replacement and correction of sodium and water deficit

      • Vasoconstrictive agents (dopamine) may be required in some extreme cases

      • Mineralocorticoid supplementation may be required (full mineralocorticoid effect will accompany the 100 mg hydrocortisone infusion)

1. Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 635-650.

2. Williams, G. H and Dluhy, R. G. , Diseases of the Adrenal Cortex, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2035-2056