Nursing Pharmacology Chapter 28: Physiology and Pharmacology: Adrenocorticosteroids / Adrenocortical Antagonists
Primary Adrenocortical insufficiency (Addison's Disease)
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Rare; may occur at any age; affects both sexes with equal frequency
Addison's disease is caused by progressive destruction of the adrenals (> 90% must be destroyed before symptoms of adrenal insufficiency appear).
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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:
Opiates
Rifampin
Phenytoin (Dilantin)
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:
Chronic lymphocytic thyroiditis
Premature ovarian failure
Type I diabetes mellitus
Hypothyroidism
Hyperthyroidism
Presence of two or more autoimmune endocrine disorders in the same patient describe polyglandular autoimmune syndrome.
Fatigue (99%) |
Weakness (99%) |
Anorexia (90%) |
Nausea (90%) |
Vomiting (90%) |
Weight loss (97%) |
Cutaneous/mucosal pigmentation (99%, 82%) |
Hypotension (87%,<than 110/70 mmHg) |
Hypoglycemia (occasionally) |
Asthenia, "Cardinal symptom"
Severe fatigue, impairment; bed rest may be necessary
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.
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
Decreased serum sodium: due to excessive urinary loss (secondary to aldosterone deficiency) and movement into intracellular compartments
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:
Aldosterone deficiency
Acidosis
Impaired glomerular filtration
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
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Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 635-650.
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