What is the appropriate acute and chronic management for Addison's disease, including glucocorticoid and mineralocorticoid replacement, stress dosing, and monitoring?

Management of Addison's Disease

Acute Management: Adrenal Crisis

Adrenal crisis requires immediate treatment with intravenous hydrocortisone 100 mg bolus, followed by continuous infusion of 200 mg over 24 hours (or 100 mg every 6-8 hours), plus aggressive fluid resuscitation with 0.9% saline at 1 L/hour until hemodynamic stability is achieved. 1

Recognition and Initial Treatment

• Suspect adrenal crisis in any patient with unexplained hypotension, volume depletion, hyponatremia (90% of cases), hyperkalemia (50% of cases), or vascular collapse 1, 2, 3
• Never delay treatment to obtain diagnostic tests—if adrenal crisis is suspected, give hydrocortisone immediately 1
• Secure blood samples for cortisol and ACTH before treatment if possible, but do not wait for results 1
• Search for and treat the precipitating cause (most commonly gastroenteritis, respiratory infections with fever, or surgical stress) once treatment is initiated 1, 2, 4

Post-Crisis Recovery

• Continue IV hydrocortisone 200 mg/24 hours until the patient can take oral medications 1
• Once oral intake is tolerated, double the usual maintenance dose for 48 hours after uncomplicated recovery 1
• For major surgery or complicated recovery, continue doubled doses for up to one week before tapering to maintenance 1

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Chronic Glucocorticoid Replacement

Most adults with Addison's disease should receive hydrocortisone 15-25 mg daily in 2-3 divided doses, with the first dose immediately upon waking and the last dose at least 6 hours before bedtime. 1, 5

Dosing Specifics

• Hydrocortisone is preferred over synthetic glucocorticoids (prednisolone, dexamethasone) because it more closely mimics physiological cortisol secretion and has fewer long-term metabolic effects 6, 7
• Alternative: cortisone acetate 20-35 mg daily in divided doses 1, 5
• Children require 8 mg/m² body surface area daily (approximately 6-10 mg/m²) 1, 5
• Use the lowest dose compatible with health and well-being 1

Monitoring Chronic Replacement

• Assess clinically at least annually: well-being, weight, blood pressure (both supine and standing to detect orthostatic hypotension), and serum electrolytes 1, 6
• Do not use serum cortisol levels to monitor adequacy of replacement—clinical assessment is the gold standard 1
• Monitor bone mineral density every 3-5 years to assess for glucocorticoid-related complications 1
• Screen periodically for new autoimmune disorders, particularly hypothyroidism with TSH and thyroid peroxidase antibodies 1

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Mineralocorticoid Replacement

All patients with primary adrenal insufficiency require fludrocortisone 50-200 mcg once daily as a single morning dose. 1, 5, 8

Dosing and Adjustments

• Most adults need 100 mcg daily; children and younger adults may require higher doses 1, 8
• Monitor plasma renin activity (PRA) and aim for the upper normal range 1, 8
• If essential hypertension develops, reduce (but do not stop) fludrocortisone 1
• Advise patients to consume salt and salty foods ad libitum; avoid licorice and grapefruit juice 1
• Check serum sodium and potassium to evaluate for adequate mineralocorticoid replacement 6, 9

Special Situations

• Pregnancy: May require increased fludrocortisone doses, particularly in the third trimester, to counteract progesterone's anti-mineralocorticoid effects 1, 8
• High ambient temperature: Dose adjustments may be needed to avoid sodium depletion 8

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Stress Dosing Protocols

Patients must double or triple their usual hydrocortisone dose during physiological stress and use parenteral hydrocortisone if vomiting prevents oral intake. 6, 9, 4

Minor Illness (fever, gastroenteritis without vomiting)

• Double the usual hydrocortisone dose for the duration of illness, typically 2-3 days 6, 9
• No taper is needed after short-term stress dosing 9

Severe Illness or Vomiting

• Triple the usual dose or switch to parenteral hydrocortisone 100 mg IM immediately 6, 9
• Seek emergency medical attention 6, 9

Surgery and Invasive Procedures

• Give hydrocortisone 100 mg IV at induction of anesthesia, followed by continuous infusion of 200 mg over 24 hours until the patient can take double their usual oral dose 1
• For uncomplicated recovery, double the oral dose for 48 hours; for major surgery, continue for up to one week 1

Pregnancy and Delivery

• Administer hydrocortisone 100 mg IV at onset of labor, then 50 mg IM every 6 hours or continuous infusion of 200 mg/24 hours until after delivery 1
• Adjust maintenance doses during the third trimester as needed 1

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Critical Patient Education

Every patient must carry an emergency steroid card, wear a medical alert bracelet, and have injectable hydrocortisone 100 mg with training for self- or family-administration. 6, 5, 4

Essential Education Points

• Recognize early warning signs of adrenal crisis: severe fatigue, nausea, vomiting, abdominal pain, confusion, hypotension 2, 4, 3
• Never abruptly stop hydrocortisone—even one week off therapy requires immediate restart at full dose, as HPA axis recovery takes months 6, 9
• Infections (especially gastroenteritis and respiratory infections) are the most common triggers of adrenal crisis 2, 4
• Patients with comorbidities (asthma, diabetes) are at higher risk for crisis 1, 2

Mortality Risk

• Adrenal crisis occurs at a rate of 6-8 episodes per 100 patient-years 1, 2, 4
• Mortality is increased 2.19-fold in men and 2.86-fold in women with adrenal insufficiency, primarily from cardiovascular, infectious, and malignant causes 1, 2
• Up to 8.6% of patients report a previous adrenal crisis caused by insufficient glucocorticoid dosing during hospitalization 1

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Common Pitfalls to Avoid

• Do not use dexamethasone in primary adrenal insufficiency—it has no mineralocorticoid activity and will not prevent crisis 1
• Do not assume HPA axis recovery after stopping exogenous steroids—testing is required at 3 months, and patients remain at risk until recovery is confirmed 6, 9
• Do not rely on serum cortisol or ACTH levels to guide chronic replacement dosing—these are not accurate in patients already taking hydrocortisone 6, 9
• Do not forget stress dosing during "minor" illnesses—failure to increase glucocorticoids during respiratory infections or gastroenteritis is a leading cause of preventable adrenal crisis 2, 9, 4
• Ward staff may dismiss patient concerns about under-replacement—patients with longstanding disease are often expert in recognizing their own warning signs and should be listened to 1