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Essentials of Diagnosis
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Deficiency of cortisol and mineralocorticoid from destruction of the adrenal cortex
Weakness, vomiting, diarrhea; abdominal pain, arthralgias; amenorrhea
Increased skin pigmentation, especially of creases, pressure areas, and nipples
Hypovolemic hypotension, small heart
Hyponatremia; hyperkalemia (may be absent with vomiting and diarrhea); hypoglycemia; eosinophilia
Elevated plasma ACTH level; cosyntropin unable to stimulate serum cortisol to 20 mcg/dL (550 nmol/L) or more
Acute adrenal crisis: above manifestations become critical, with fever, shock, confusion, coma, death
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General Considerations
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Refers to chronic deficiency of cortisol caused by adrenocortical insufficiency
Acute adrenal (Addisonian) crisis
An emergency caused by insufficient cortisol
May occur in the course of treatment of chronic adrenal insufficiency
May be the presenting manifestation of adrenal insufficiency
Causes of primary adrenal insufficiency
Autoimmunity
Accounts for about 90% of spontaneous cases
Over half the cases of autoimmune Addison disease occur as part of autoimmune polyendocrine syndrome type-I, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome
Bilateral adrenal infiltrative diseases
Cause primary adrenal insufficiency
Causative neoplasms include lymphomas, breast cancer, and lung cancer
Infections
Tuberculosis
Coccidiomycosis
Histoplasmosis
Cytomegalovirus
Cryptococcus
Syphilitic gummas
Bilateral adrenal hemorrhage
Adrenoleukodystrophy
Congenital adrenal insufficiency occurs in several conditions
Familial glucocorticoid deficiency
Triple A (Allgrove) syndrome
Congenital adrenal hypoplasia
Rare causes of primary adrenal insufficiency
Lymphoma, metastatic carcinoma
Coccidioidomycosis, histoplasmosis, cytomegalovirus infection (more frequent in patients with AIDS)
Syphilitic gummas
Scleroderma
Amyloidosis
Hemochromatosis
Drugs that cause primary adrenal insufficiency include
Mitotane
Abiraterone acetate
Lenvatinib
Vandetanib
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Abdominal pain, nausea, and vomiting; diarrhea can occur
Fevers and lymphoid tissue hyperplasia may also occur
Arthralgias, myalgias, chest pain, abdominal pain, back pain, leg pain, or headache
Psychiatric symptoms: anxiety, irritability, and depression
Low and orthostatic blood pressure
Skin hyperpigmentation and scant axillary and pubic hair
Anovulation and reduced fertility
Recurrent hypoglycemia and reduced insulin requirements in patients with preexisting type 1 diabetes mellitus
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Differential Diagnosis
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Other cause of shock
Sepsis
Cardiogenic
Hypovolemic
Hyperkalemia due to other cause (see Hyperkalemia)
Hyponatremia due to other cause (see Hyponatremia)
Abdominal pain due to other cause
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One or more serum anti-adrenal antibodies are found in about 50% of cases of autoimmune disease
Mild anemia, moderate neutropenia, lymphocytosis, and eosinophilia (total eosinophil count > 300/mcL)
Hyponatremia or hyperkalemia (or both) usually present
Hypoglycemia common
Hypercalcemia may be present
Blood, sputum, or urine culture may be positive if bacterial infection is precipitating cause
Cosyntropin stimulation test