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| Addison's disease |
Adrenal hypofunction from primary disease (partial or complete destruction) of the adrenal gland with inadequate secretion of glucocorticoids and mineralocorticoids. An autoimmune process is the most common cause (80% of the cases) followed by tuberculosis. AIDS is becoming a more frequent cause.
•Addison's disease (primary adrenocortical insufficiency) is differentiated from secondary (pituitary failure) and tertiary (hypothalamic failure) causes of adrenocortical insufficiency (see Differential Diagnosis)
•Addisonian (adrenal) crisis - acute complication of adrenal insufficiency (circulatory collapse, dehydration, hypotension, nausea, vomiting, hypoglycemia); usually precipitated by acute physiologic stressor such as surgery, illness, exacerbation of co-morbid process, acute withdrawal of long term corticosteroid therapy
Genetics:
Autoimmune adrenal insufficiency shows some hereditary disposition. Familial glucocorticoid insufficiency may have recessive pattern; adrenomyeloneuropathy is X-linked. Frequent association with other autoimmune disorders.
Incidence/Prevalence in USA:
Predominant age:
- All ages; usually 3rd to 5th decade
Predominant sex:
SIGNS AND SYMPTOMS:
•Weakness, fatigue, tiredness
•Weight loss
•Dizziness; low blood pressure, orthostatic hypotension
•Increased pigmentation (extensor surfaces, hand creases, dental-gingival margins, buccal and vaginal mucosa, lips, areola, pressure points, scars; "tanning"; freckles; vitiligo)
•Anorexia; nausea; vomiting
•Chronic diarrhea
•Abdominal pain
•Decreased cold tolerance
•Salt craving
•Hair loss in females
•Depression (60-80% of patients)
CAUSES:
•Autoimmune adrenal insufficiency (~80%)
•Tuberculosis (~20%)
•Waterhouse-Friderichsen syndrome (disseminated adrenal infection and subsequent infarction; meningococcemia most common; Pseudomonas aeruginosa common in children; atypical pathogens, CMV, Cryptococcus, MAC in immunosuppressed and AIDS)
•Fungal disease (histoplasmosis, blastomycosis, coccidioidomycosis)
•Bilateral adrenal hemorrhage and infarction (anticoagulants; 50% are in therapeutic range at time of hemorrhage)
•Antiphospholipid syndrome
•Metastatic (lung, breast, kidney, colon), lymphoma, Kaposi's sarcoma (tumor must destroy 90% of gland to produce hypofunction)
•Drugs (ketoconazole, etomidate)
•Surgical adrenalectomy
•Radiation therapy
•Sarcoidosis
•Hemochromatosis
•Amyloidosis
•Adrenoleukodystrophy
•Adrenomyelodystrophy
•Polyglandular endocrine syndromes
•APS I (autoimmune polyglandular syndrome 1)
•Childhood onset
•HLA-DR not associated
•Single gene mutation in APECED gene (APECED = autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy)
•APS II (autoimmune polyglandular syndrome II)
•Schmidt's syndrome
•Adult onset
•HLA-DR associated
•Adrenal failure with type I diabetes mellitus and/or hypothyroidism
•Congenital (enzyme defects; hypoplasia; familial glucocorticoid insufficiency)
•Idiopathic
RISK FACTORS:
•Family history of autoimmune adrenal insufficiency. About 40% of patients have a first- or second-degree relative with one of the associated disorders.
•Taking steroids for prolonged periods, then experiencing severe infection, trauma or surgical procedures
DIAGNOSIS DIFFERENTIAL DIAGNOSIS:
•Secondary adrenocortical insufficiency
•Withdrawal of long-term corticosteroid use
•Sheehan's syndrome (postpartum necrosis of pituitary)
•Empty sella syndrome
•Surgical excision of pituitary
•Radiation to pituitary
•Pituitary adenomas, carcinomas (rare), craniopharyngiomas
•Infiltrative disorders of pituitary (sarcoidosis, hemochromatosis, amyloidosis, histiocytosis X)
•Megestrol
•Tertiary adrenocortical insufficiency
•Pituitary stalk transection
•Trauma
•Disruption of production of corticotropic releasing factor (CRF)
•Hypothalamic tumors
•Myopathies
•Syndrome of inappropriate antidiuretic hormone (SIADH)
•Heavy metal ingestion
•Severe nutritional deficiencies
•Sprue syndrome
•Hyperparathyroidism
•Neurofibromatosis
•Peutz-Jeghers syndrome
•Porphyria cutanea tarda
•Salt-losing nephritis
•Bronchogenic carcinoma
•Anorexia nervosa
•Other causes of hypoglycemia
•Depression
LABORATORY:
•Low serum sodium
•Elevated serum potassium
•Elevated BUN, creatinine
•Elevated serum calcium
•Hypoglycemia when fasted
•Metabolic acidosis
•Low cortisol level (between 8 and 9 a.m.)
•Elevated ACTH level
•Moderate neutropenia
•Eosinophilia
•Relative lymphocytosis
•Anemia
•Adrenal-cortex autoantibody (ACA/21-hydroxylase)
PATHOLOGICAL FINDINGS:
Atrophic adrenals in autoimmune adrenalitis. Infiltrative and hemorrhagic disorders produce enlargement with destruction of entire gland.
SPECIAL TESTS:
•Rapid ACTH stimulation test: Cosyntropin 0.25 mg IV, measure pre-injection and 60 minute post-injection cortisol levels. Patients with Addison's disease have low to normal values that do not rise
•Metapyrone test
•Insulin-induced hypoglycemia test
•CRH may help distinguish secondary from tertiary adrenal insufficiency
•Autoantibody tests
•21-Hydroxylase (most common and specific)
•17-Hydroxylase
•17-alfa-Hydroxylase (may not be associated)
•Adrenomedullin
IMAGING:
•Abdominal CT scan
•Small adrenal glands in autoimmune adrenalitis
•Enlarged adrenal glands in infiltrative and hemorrhagic disorders
•Abdominal x-ray: may show adrenal calcifications
•Chest x-ray: may show adrenal calcifications, small heart size, calcification of cartilage
DIAGNOSTIC PROCEDURES:
A work-up to determine the cause of Addison's disease. CT guided fine-needle biopsy of adrenal masses may be helpful.
GENERAL MEASURES:
•Treatment for adrenal insufficiency is with glucocorticoid and mineralocorticoid replacement
•5 S's of management of adrenal crisis: salt, sugar, steroids, support, search for precipitating illness
•Appropriate treatment for underlying cause (e.g., tuberculosis)
DIET:
Arrange for a diet that maintains water, sodium and potassium balances
PATIENT EDUCATION:
•For patient education materials favorably reviewed on this topic, contact: National Addison's Disease Foundation, 505 Northern Blvd., Suite 200, Great Neck, NY 11021, (516)487-4992
•Patient should wear or carry medical identification with information about the disease and the need for hydrocortisone or other replacement therapy
•Instruct patient in self-administering of parenteral hydrocortisone for emergency situations (e.g., traveling in remote areas away from medical help)
MEDICATIONS
DRUG(S) OF CHOICE:
•For chronic adrenal insufficiency:
•Hydrocortisone 15-20 mg orally each morning upon arising and 10 mg at 4-5 each afternoon is usual dosage (dosage may vary and is usually less in children's),PLUS,
•Fludrocortisone 0.05-0.2 mg orally once/day plus
•Dehydroepiandrosterone 25-50 mg orally once a day (monitor lipid profile, breast or prostate cancer)
•Acute adrenal insufficiency
•Hydrocortisone hemisuccinate 100 mg IV followed by 10 mg/hr infusion
•IV glucose, saline, plasma expanders
•For acute illnesses (fever, stress, minor trauma)
•Double the patient's usual steroid dose
PREVENTION/AVOIDANCE:
•No preventive measures known for Addison's disease
•Prevention of complications
•Anticipate adrenal crisis and treat before symptoms begin
•If nausea and vomiting preclude oral therapy, patient should seek medical help to start parenteral therapy
•Elective surgical procedures require adjustment in steroid dose
•Prevent exposure to infections
POSSIBLE COMPLICATIONS:
•Hyperpyrexia
•Psychotic reactions
•Complications from underlying disease
•Over- or under-steroid treatment
•Hyperkalemic paralysis (rare)
•Addisonian crisis
EXPECTED COURSE AND PROGNOSIS:
•Good outlook with appropriate treatment. With adequate replacement therapy, life expectancy approximates normal
•100% lethal without treatment |
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