What is the primary treatment for adrenal insufficiency?

Primary Treatment for Adrenal Insufficiency

The primary treatment for adrenal insufficiency consists of glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, combined with mineralocorticoid replacement using fludrocortisone 50-200 µg once daily for patients with primary adrenal insufficiency. 1, 2

Glucocorticoid Replacement

Hydrocortisone is the preferred glucocorticoid and should be administered in a total daily dose of 15-25 mg divided into 2-3 doses throughout the day. 1, 2, 3, 4 The American College of Endocrinology and Endocrine Society both emphasize using the lowest dose compatible with health and well-being to minimize long-term complications of glucocorticoid excess. 1

Optimal Dosing Schedule

• The first dose should be taken immediately upon waking, with subsequent doses spaced throughout the day. 2
• A common three-dose schedule is 10 mg + 5 mg + 2.5 mg (morning, midday, afternoon). 2
• The last dose should be taken at least 6 hours before bedtime to avoid sleep disturbances. 2
• Cortisone acetate can serve as an alternative at 18.75-31.25 mg daily in divided doses, or prednisone 3-5 mg daily. 2, 4

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone 50-200 µg once daily in the morning is essential for all patients with primary adrenal insufficiency, as they lack aldosterone production. 1, 2, 5 This is a critical distinction—patients with secondary adrenal insufficiency do not require mineralocorticoid replacement because their renin-angiotensin-aldosterone system remains intact. 4

Dosing Considerations

• Higher doses up to 500 µg daily may be needed in children, younger adults, or during the last trimester of pregnancy when progesterone counteracts mineralocorticoids. 6, 2
• Patients should consume salt and salty foods without restriction and avoid potassium-containing salt substitutes. 6, 2
• The fludrocortisone dose is guided by clinical parameters: blood pressure (supine and standing), presence of peripheral edema, salt cravings, and lightheadedness. 6, 2

Critical Medication Interactions to Avoid

Several medications can dangerously interact with fludrocortisone and must be avoided or carefully managed:

• Diuretics, acetazolamide, NSAIDs, and carbenoxolone should be avoided entirely. 6, 1, 2
• Licorice and grapefruit juice potentiate mineralocorticoid effects and should be avoided. 6, 2
• Drospirenone-containing contraceptives may require increased fludrocortisone dosing. 6, 2
• Anti-epileptic drugs, barbiturates, and antituberculosis medications may increase hydrocortisone requirements. 6, 2

Stress Dosing Protocols

During minor illnesses with fever, the usual glucocorticoid dose should be doubled or tripled. 2 For major surgery, 100 mg hydrocortisone IM/IV should be administered just before anesthesia, followed by 100 mg every 6 hours until the patient can eat and drink. 1, 2

Adrenal Crisis Management

Adrenal crisis requires immediate treatment with 100 mg hydrocortisone IV bolus, followed by 100 mg every 6-8 hours, plus rapid IV administration of isotonic saline at 1 L/hour initially, then 3-4 L over 24 hours. 1, 2, 4 This is a life-threatening emergency that can cause hypotension, shock, hyponatremia, altered mental status, and death if untreated. 4

Essential Patient Education and Safety Measures

All patients must wear medical alert identification jewelry and carry a steroid alert card. 1, 2 They should be prescribed injectable hydrocortisone (100 mg IM) for self-administration during emergencies when oral intake is impossible. 1, 2

Common precipitating factors for adrenal crisis include gastrointestinal illness with vomiting/diarrhea, infections, surgical procedures, injuries, and severe allergic reactions. 2

Monitoring and Follow-Up

Annual follow-up should assess symptoms, weight, blood pressure, serum sodium, potassium, glucose, HbA1c, and complete blood count. 2 Screening for associated autoimmune conditions, particularly thyroid dysfunction (TSH, FT4, TPO-Ab) and vitamin B12 levels, should be performed. 2

Signs of Inadequate vs. Excessive Replacement

• Under-replacement: Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation (in primary AI). 2
• Over-replacement: Weight gain, hypertension, edema, Cushing-like symptoms. 2, 7

Common Pitfalls

Under-replacement with mineralocorticoids is common and sometimes compensated for by over-replacement of glucocorticoids, which predisposes patients to recurrent adrenal crises. 6, 2 This is a dangerous pattern that must be recognized and corrected.

If essential hypertension develops, treat with vasodilators rather than stopping mineralocorticoid replacement—though a dose reduction should be considered. 6, 2 Never discontinue fludrocortisone entirely in primary adrenal insufficiency, as this risks adrenal crisis.

Recent data from the past 10-15 years show that morbidity remains high and life expectancy is reduced with conventional glucocorticoid replacement therapy, likely due to both increased cortisol exposure and insufficient cortisol coverage during stress-related events. 7 This underscores the importance of individualized dosing and proper stress-dose education.