What is the recommended treatment approach for primary adrenal insufficiency?

Treatment of Primary Adrenal Insufficiency

All patients with primary adrenal insufficiency require lifelong replacement therapy with both glucocorticoids and mineralocorticoids, along with patient education on stress dosing and emergency management to prevent life-threatening adrenal crisis. 1, 2

Core Replacement Therapy

Glucocorticoid Replacement

The cornerstone of treatment is hydrocortisone 15-25 mg daily in divided doses, with the first dose taken immediately upon waking and the last dose at least 6 hours before bedtime. 1, 3

• Hydrocortisone is preferred over synthetic glucocorticoids as first-line therapy due to better physiological mimicry and fewer long-term metabolic effects 4
• Alternative options include cortisone acetate 18.75-31.25 mg daily or prednisone 3-5 mg daily 1, 5, 3
• In children, dose hydrocortisone at 6-10 mg/m² of body surface area 1
• Use the lowest dose compatible with health and sense of well-being to minimize long-term complications of glucocorticoid excess 1

Mineralocorticoid Replacement

Fludrocortisone 50-200 µg (0.05-0.2 mg) once daily in the morning is essential for all patients with primary adrenal insufficiency. 1, 2, 3

• Most patients require 100 µg (0.1 mg) as a starting dose 6
• Children and younger adults typically require higher doses per body surface area 1, 6
• Monitor clinically by assessing salt cravings, lightheadedness, blood pressure (supine and standing), and peripheral edema 1
• Monitor biochemically with serum sodium, potassium, and blood pressure 1, 6
• If essential hypertension develops, reduce the fludrocortisone dose but never stop it completely as this risks adrenal crisis 1, 6

Dietary Recommendations

• Advise patients to consume salt and salty foods ad libitum 1
• Avoid potassium-containing salt substitutes 7
• Avoid liquorice and grapefruit juice as they potentiate mineralocorticoid effects 1, 7

Medication Interactions to Avoid

Several medications interact with fludrocortisone and should be avoided or require dose adjustment: 1, 6

• Diuretics - avoid completely
• Acetazolamide - avoid completely
• NSAIDs - avoid completely
• Carbenoxolone - avoid completely
• Drospirenone-containing contraceptives may require increased fludrocortisone doses 1, 6

Stress Dosing Protocols

Surgery and Medical Procedures

For major surgery, administer 100 mg hydrocortisone IM/IV just before anesthesia, then continue 100 mg every 6 hours until the patient can eat and drink. 1

• Major surgery with long recovery: Continue 100 mg every 6 hours until oral intake resumes, then double oral dose for 48+ hours before tapering 1
• Major surgery with rapid recovery: Continue 100 mg every 6 hours for 24-48 hours, then double oral dose for 24-48 hours before tapering 1
• Minor surgery and major dental procedures: 100 mg IM/IV before anesthesia, then double oral dose for 24 hours 1

Pregnancy and Delivery

During the third trimester, increase hydrocortisone by 2.5-10 mg daily and monitor for need to increase fludrocortisone due to progesterone's anti-mineralocorticoid effects. 1

• At onset of labor, give 100 mg hydrocortisone IM, repeat every 6 hours if necessary 1
• Postpartum, double oral dose for 24-48 hours then taper to normal 1
• Monitor blood pressure and electrolytes rather than plasma renin activity during pregnancy 1

Physical Activity

• Regular, accustomed exercise does not require dose adjustment 1
• For intense or prolonged exercise (e.g., marathon), take an extra 5 mg hydrocortisone before the event 1
• Increase fluid and salt intake during hot conditions or intense activity 1

Adrenal Androgen Replacement (Optional)

DHEA replacement is not routinely recommended but may be offered as a 6-month trial to women with persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement. 1

• Dose: 25 mg daily (range 10-50 mg) as a single morning dose 1
• Monitor serum DHEA sulfate, androstenedione, and testosterone levels in the morning before DHEA ingestion 1
• Continue only if clinically effective after 6 months 1
• Use with caution as long-term effects are unknown and evidence of benefit from large studies is limited 1

Emergency Management of Adrenal Crisis

Adrenal crisis is a life-threatening emergency requiring immediate treatment - never delay for diagnostic procedures. 1, 8

• Give 100 mg hydrocortisone IV or IM immediately 1, 3
• Continue 100 mg hydrocortisone every 6-8 hours until recovered 1
• Infuse 0.9% sodium chloride solution at 1 L/hour initially until hemodynamic improvement 1
• Identify and treat the underlying precipitant (e.g., infection) 1
• Even mild gastrointestinal upset can precipitate crisis as patients cannot absorb oral medication when they need it most 1

Essential Patient Education

All patients must receive comprehensive education and emergency supplies: 1, 3

• Wear medical alert identification jewelry and carry a steroid alert card 1
• Provide supplies for self-injection of parenteral hydrocortisone (100 mg IM) 1
• Educate on managing daily medications and minor to moderate concurrent illnesses 1
• Teach stress dosing: double or triple oral dose during febrile illness or significant stress 3, 9

Monitoring and Follow-Up

Review patients at least annually with assessment of: 1

• Health, well-being, and weight
• Blood pressure (supine and standing)
• Serum electrolytes (sodium and potassium)
• Screening for new autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density every 3-5 years to assess for complications of glucocorticoid therapy 1

Common Pitfalls to Avoid

• Under-replacement of mineralocorticoids is common and sometimes compensated for by over-replacement of glucocorticoids, predisposing to recurrent adrenal crises 1, 7
• Do not rely solely on plasma renin activity for fludrocortisone dosing - use clinical parameters (blood pressure, salt cravings, electrolytes) 1, 6
• Avoid synthetic glucocorticoids (prednisolone, dexamethasone) as first-line therapy due to undesirable long-term metabolic effects 4
• Never discontinue fludrocortisone completely, even if hypertension develops - reduce the dose instead 1, 6