What is the primary treatment for a patient with hypoadrenalism (adrenal insufficiency)?

Primary Treatment for Hypoadrenalism (Adrenal Insufficiency)

The primary treatment for adrenal insufficiency is lifelong glucocorticoid replacement therapy with hydrocortisone 15-25 mg daily in divided doses, plus fludrocortisone 50-200 μg daily for patients with primary adrenal insufficiency who lack mineralocorticoid production. 1, 2, 3, 4

Glucocorticoid Replacement

Standard Dosing Regimen

• Hydrocortisone 15-25 mg daily is the preferred glucocorticoid, divided into 2-3 doses to mimic physiologic cortisol secretion 1, 2, 5
• The first dose should be taken immediately upon waking, with the last dose no less than 6 hours before bedtime to preserve circadian rhythm 2
• A typical twice-daily regimen is 15 mg upon waking and 5 mg in early afternoon 1
• A thrice-daily regimen (e.g., 10 mg, 5 mg, 5 mg) provides more physiologic cortisol levels and may be superior, particularly for avoiding afternoon/evening cortisol nadirs 6

Alternative Glucocorticoids

• Cortisone acetate 25-37.5 mg daily in divided doses is an acceptable alternative 1, 7
• Prednisolone 4-5 mg daily can be used but lacks the short half-life that mimics physiologic cortisol 8
• Use the lowest dose compatible with health and well-being to minimize long-term complications like osteoporosis and cardiovascular disease 1, 2

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone Dosing

• Fludrocortisone 50-200 μg once daily in the morning is required for all patients with primary adrenal insufficiency 1, 2, 4, 9
• Secondary adrenal insufficiency does NOT require mineralocorticoid replacement because the renin-angiotensin-aldosterone system remains intact 8

Monitoring and Adjustment

• Titrate fludrocortisone based on blood pressure (target normotension, avoid postural hypotension), serum potassium (target normokalemia), and plasma renin activity (target upper normal range) 1, 2, 9
• Common pitfall: Many patients remain chronically underreplaced with mineralocorticoids, evidenced by persistent salt craving, postural dizziness, and low blood pressure despite treatment 9
• Supine and standing blood pressure should be measured at each visit 1

Emergency Treatment: Adrenal Crisis

Immediate Management

• Never delay treatment for diagnostic testing if adrenal crisis is suspected 1, 8, 10
• Administer hydrocortisone 100 mg IV bolus immediately, followed by 100 mg every 6-8 hours (or 200-300 mg/day as continuous infusion) 1, 2, 3
• Simultaneously infuse 0.9% normal saline at 1 L/hour initially, then 3-4 L over 24 hours with hemodynamic monitoring 1, 2
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy 1, 10

Alternative for Uncertain Diagnosis

• If you need to treat suspected crisis but want to preserve diagnostic testing capability, use dexamethasone 4 mg IV instead of hydrocortisone, as it does not interfere with cortisol assays 8, 10

Tapering After Crisis

• Taper parenteral hydrocortisone over 1-3 days to oral maintenance doses as clinical condition improves 1
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Patient Education and Crisis Prevention

Essential Patient Instructions

• All patients must wear medical alert identification (bracelet/necklace) and carry a steroid emergency card 2, 11
• Provide injectable hydrocortisone for home use and train patients/family in self-administration for vomiting or severe illness 11
• Stress dosing protocol: Double or triple maintenance glucocorticoid dose during febrile illness, vomiting, diarrhea, or significant stress 1, 7
• For minor illness (fever <38°C), double the dose; for moderate illness (fever >38°C), triple the dose 1
• Seek immediate medical attention if unable to take oral medications or if symptoms worsen despite increased dosing 1, 11

High-Risk Scenarios

• Patients taking ≥20 mg/day prednisone (or equivalent) for ≥3 weeks are at high risk for HPA axis suppression and should be presumed to have adrenal insufficiency if they develop unexplained hypotension 8, 10
• Adrenal crisis is precipitated by infections (especially gastroenteritis), surgery, trauma, myocardial infarction, or medication non-compliance, occurring at a rate of 6-8 episodes per 100 patient-years 1

Follow-Up and Monitoring

Annual Assessment

• Review symptoms of under-replacement (fatigue, nausea, weight loss, postural hypotension, salt craving) and over-replacement (weight gain, hypertension, hyperglycemia, osteoporosis) 1, 2
• Measure weight, blood pressure (supine and standing), and serum electrolytes 1, 2
• Screen for associated autoimmune conditions annually in primary adrenal insufficiency: thyroid function, fasting glucose, complete blood count, vitamin B12, and tissue transglutaminase antibodies 1, 10
• Monitor bone mineral density every 3-5 years to detect glucocorticoid-induced osteoporosis 2

Common Pitfall

• Do not use cortisol levels or day curves to adjust chronic replacement therapy, as there is no validated target range and significant inter-individual variation exists 1, 6
• Clinical assessment (symptoms, blood pressure, weight, electrolytes) is more reliable than biochemical monitoring for dose adjustment 1, 2

Special Considerations

Concurrent Hypothyroidism

• Always start glucocorticoid replacement several days before initiating thyroid hormone replacement in patients with both conditions, as thyroid hormone can precipitate adrenal crisis by increasing cortisol metabolism 8

Morning Nausea

• If patients experience morning nausea and poor appetite, consider taking the first hydrocortisone dose 30-60 minutes earlier upon waking, then returning to sleep briefly before rising 8
• This symptom often indicates glucocorticoid under-replacement 8