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

• Primary Adrenocortical insufficiency (Addison's Disease)

  • "What is Addison's Disease?"

    Learnnursing:  "What is Addison's Disease" https://www.youtube.com/watch?v=FK1pPqWMXjM http://learnursing.com/pages/home.html

  • Overview 

    • Rare; may occur at any age; affects both sexes with equal frequency

  • Etiology/Pathogenesis

    • Addison's disease is caused by progressive destruction of the adrenals (> 90% must be destroyed before symptoms of adrenal insufficiency appear).

     

    • Atrophic adrenal, gross, in chronic adrenocortical insufficiency

      "Atrophic adrenal, gross, in chronic adrenocortical insufficiency "; KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center.

• Adrenal gland destruction

  •  Adrenal is a common site for chronic granulomatous diseases such as:

    • Tuberculosis (mainly)

    • Histoplasmosis

    • Coccidiodomycosis

    • Cryptococcosis

  •  Adrenoleukodystrophy is associated with both significant demyelination and early death in children.

  •  Adrenomyeloneuropathy is characterized by mixed motor/sensory neuropathy with spastic paraplegia affecting primarily adults.

  •  AIDS patients may exhibit a higher likelihood of adrenal-insufficiency because of the following factors:

    • Cytomegalovirus frequently involves the adrenal glands

      • CMV necrotizing adrenalitis

      • Involvement with Mycobacterium avium intracellulare, Cryptococcus, and Kaposi sarcoma

      • Note: in interpreting results from adrenal function test in AIDS patients that certain medications may potentiates adrenal insufficiency including:

        1. Opiates

        2. Rifampin

        3. Phenytoin (Dilantin)

        4. Ketoconazole (Nizoral)

  • In early described cases, tuberculosis caused 70%-90% of cases.

  • Most frequent cause today is idiopathic atrophy.

    • Autoimmune mechanism, which is considered one of the most likely causes.

    • Half of patients are found to have circulating adrenal antibodies.

      • Adrenal antigens

        • Some antibodies may cause adrenal destruction

        • Other antibodies may cause adrenal insufficiency by inhibiting ACTH binding

        • Some individuals also have antibodies to thyroid, parathyroid, and/or gonadal tissue

    • Increased likelihood of:

      1. Chronic lymphocytic thyroiditis

      2. Premature ovarian failure

      3. Type I diabetes mellitus

      4. Hypothyroidism

      5. Hyperthyroidism

    • Presence of two or more autoimmune endocrine disorders in the same patient describe polyglandular autoimmune syndrome.

• Presenting Clinical Signs and Symptoms

• Asthenia, "Cardinal symptom"

  • Severe fatigue, impairment; bed rest may be necessary

• Hyperpigmentation

  • Diffuse brown, tan, bronze darkening at elbows, hand creases

  • May include bluish-black mucosal membrane patches

• Arterial hypotension with orthostatic component.

• Gastrointestinal disturbances represent a frequent presenting symptom.

• Primary Adrenocortical insufficiency: Laboratory Findings and Diagnostic Testing.

  •  Laboratory findings:

    • Initially:steroid output normal; but adrenal reserve reduced

      • ACTH-adrenal stimulation: produces some normal cortisol increase or no increase

    • More advanced disease: (more adrenal destruction)

      •  Serum sodium, bicarbonate, chloride: reduced

        1. Decreased serum sodium: due to excessive urinary loss (secondary to aldosterone deficiency) and movement into intracellular compartments

        2. extravascular sodium loss -- depleting extracellular fluid; promotes hypotension; elevated plasma angiotensin II and vasopressin promote hyponatremia by reducing free water clearance

      •  Serum potassium: elevated

        • Hyperkalemia due to:

          1. Aldosterone deficiency

          2. Acidosis

          3. Impaired glomerular filtration

  •  Diagnosis:

    • Based on ACTH stimulation testing: evaluation of adrenal steroid production reserve capacity

    • Severe adrenal insufficiency: rate of cortisol secretion significantly reduced; low to absent 24 urine cortisol levelto

    • Mild adrenal insufficiency (decreased adrenal reserve)

    • Aldosterone secretion: low-- causing:

      • Salt wasting

      • Increased plasma renin

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