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KEY FEATURES

ESSENTIALS OF DIAGNOSIS

  • Inability to increase serum cortisol to > 20 mg/dL in response to synthetic adrenocorticotropic hormone (ACTH) during rapid ACTH stimulation testing

  • Orthostatic hypotension, urinary salt wasting, and serum hyperkalemia in primary adrenal insufficiency (Addison’s disease)

  • Hyponatremia in both primary and secondary (pituitary) adrenal insufficiency

  • Elevated ACTH in Addison’s disease

  • Hypovolemic shock, hypoglycemia, and fever in adrenal crisis

GENERAL CONSIDERATIONS

  • Primary adrenal insufficiency (Addison’s disease) is caused by destruction of the adrenal cortex usually by an autoimmune disease today (granulomatous diseases such as tuberculosis in the past)

  • Secondary adrenal insufficiency is usually caused by withdrawal of steroids, which depress the hypothalamic pituitary adrenal axis resulting in ACTH hyposecretion, which leads to decreased adrenal glucocorticoid production

  • Incidence in the general population is < 0.01%, but occurs more commonly in critically ill patients, especially those over age 55 who are hypotensive

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

  • Fatigue

  • Anorexia, nausea, vomiting, abdominal pain, weight loss

  • Depressed mentation, syncope, coma

PHYSICAL EXAM FINDINGS

  • Hyperpigmented skin if chronic; vitiligo if autoimmune

  • Decreased pubic and axillary hair

  • Dehydration

  • Hypotension

  • Fever

DIFFERENTIAL DIAGNOSIS

  • Other causes of orthostatic hypotension

  • Other causes of hypovolemic shock

  • Other causes of hyperkalemia, hyponatremia, hypercalcemia, hypoglycemia, and acidosis

DIAGNOSTIC EVALUATION

LABORATORY TESTS

  • Electrolytes and glucose show: hyponatremia, hyperkalemia (if primary), hypercalcemia, hypoglycemia, and acidosis

  • CBC: anemia, lymphocytosis, and eosinophilia

  • Serum cortisol < 25 mg/dL in critically ill patients; elevated in primary adrenal insufficiency

ELECTROCARDIOGRAPHY

  • Sinus bradycardia or tachycardia

  • Nonspecific ST-T–wave changes

  • Signs of hyperkalemia (peaked T waves)

  • Short QT if hypercalcemic

IMAGING STUDIES

  • Echocardiogram shows small cardiac chambers with normal function

DIAGNOSTIC PROCEDURES

  • Rapid ACTH stimulation test causes cortisol to increase to ≥ 20 mg/dL in primary adrenal insufficiency

TREATMENT

CARDIOLOGY REFERRAL

  • Significant cardiac arrhythmias

HOSPITALIZATION CRITERIA

  • Suspected adrenal insufficiency

MEDICATIONS

  • Hydrocortisone 100 mg IV every 6–8 hours acutely

  • Saline and glucose IV

  • Treatment of precipitating infection

  • Long-term adrenal hormone replacement, such as hydrocortisone PO 20 mg in the morning and 10 mg in the evening, plus fludrocortisone 0.05–0.1 mg PO daily in primary adrenal insufficiency

MONITORING

  • ECG in hospital as appropriate

DIET AND ACTIVITY

  • High-sodium diet and fluids until condition is controlled by therapy

  • Restricted activity until treatment is underway

ONGOING MANAGEMENT

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