What oral steroid is best to use in place of Cortef (hydrocortisone) for adrenal insufficiency when oral Cortef is not available?

Alternative Oral Steroids for Adrenal Insufficiency When Hydrocortisone is Unavailable

Prednisone or prednisolone are the best oral alternatives to hydrocortisone (Cortef) for adrenal insufficiency when hydrocortisone is unavailable, with a typical replacement dose of 4-5 mg daily. 1, 2

Recommended Alternative Glucocorticoids

First-Line Alternative: Prednisone/Prednisolone

• Use prednisone 4-5 mg daily or prednisolone 4-5 mg daily as the primary alternative to hydrocortisone for maintenance glucocorticoid replacement. 1, 2
• The conversion ratio is approximately hydrocortisone 20 mg = prednisone 5 mg, meaning if a patient was taking hydrocortisone 20 mg daily, substitute with prednisone 5 mg daily. 2
• For typical hydrocortisone dosing of 15-25 mg daily, the equivalent prednisone dose would be approximately 3.75-6.25 mg daily, rounded to 4-5 mg. 1, 3

Second-Line Alternative: Cortisone Acetate

• Cortisone acetate 25-37.5 mg daily in divided doses is an acceptable alternative glucocorticoid replacement. 1
• This option may be less readily available than prednisone but remains a viable choice when hydrocortisone is unavailable. 1

Critical Steroids to AVOID for Chronic Replacement

Never use dexamethasone or betamethasone for chronic adrenal insufficiency replacement therapy. 4, 5

• These long-acting steroids produce prolonged adrenal cortical suppression (>2 days following a single dose) and are specifically contraindicated for maintenance replacement therapy. 5
• Dexamethasone lacks mineralocorticoid activity and causes excessive HPA axis suppression, making it unsuitable for daily replacement. 4, 5
• Dexamethasone should only be reserved for acute crisis situations when diagnostic testing is still needed, as it doesn't interfere with cortisol assays. 1

Dosing Considerations and Adjustments

Maintenance Dosing

• Standard hydrocortisone replacement is 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg noon, 5 mg afternoon). 1, 4
• When converting to prednisone, give as a single morning dose of 4-5 mg, or split into 3 mg morning and 2 mg afternoon if the patient experiences energy fluctuations. 1

Stress Dosing with Alternative Steroids

• For mild stress (fever, minor illness): double the usual prednisone dose (e.g., if taking 5 mg daily, increase to 10 mg daily). 2, 4
• For moderate stress: prednisone 20 mg daily. 2
• For severe stress or adrenal crisis: immediately switch to parenteral hydrocortisone 100 mg IV bolus, followed by 50 mg IV every 6 hours or 200 mg/24 hours continuous infusion—do not attempt to manage severe stress with oral prednisone alone. 2, 4, 6

Mineralocorticoid Replacement Remains Essential

• All patients with primary adrenal insufficiency (Addison's disease) require fludrocortisone 0.05-0.2 mg daily in addition to glucocorticoid replacement, regardless of which glucocorticoid is used. 1, 2, 3
• Neither prednisone nor prednisolone provides adequate mineralocorticoid activity at physiologic replacement doses. 4
• Only hydrocortisone provides some mineralocorticoid activity at physiologic doses, but even then, patients with primary AI still require fludrocortisone. 4, 3
• Patients with secondary adrenal insufficiency do not require mineralocorticoid replacement as their renin-angiotensin-aldosterone system remains intact. 1

Important Caveats When Using Prednisone/Prednisolone

Loss of Diurnal Rhythm

• Prednisone has a longer half-life than hydrocortisone, making it impossible to recreate the normal diurnal cortisol rhythm. 2
• This may result in less physiologic replacement, though many patients tolerate it well. 1

When to Consider Prednisone Over Hydrocortisone

• Prednisone may be preferable in select patients who experience marked fluctuations in energy or well-being throughout the day on hydrocortisone. 1
• The longer duration of action provides more stable coverage but at the cost of less physiologic dosing. 1

Monitoring and Titration

• Monitor for signs of under-replacement: persistent fatigue, nausea, weight loss, salt craving, orthostatic hypotension. 1
• Monitor for signs of over-replacement: weight gain, hypertension, hyperglycemia, cushingoid features. 1
• Adjust fludrocortisone based on blood pressure (supine and standing), salt cravings, and plasma renin activity. 1, 2

Emergency Preparedness Remains Mandatory

• All patients must carry an emergency injectable hydrocortisone 100 mg IM kit with self-injection training, regardless of which oral steroid they take for maintenance. 2, 4
• Patients must wear a medical alert bracelet or necklace indicating adrenal insufficiency. 1, 2
• Education on stress dosing and recognition of adrenal crisis signs is essential. 2, 7

Alternative Emergency Options If Hydrocortisone Unavailable

• If parenteral hydrocortisone is unavailable during an adrenal crisis, prednisolone or methylprednisolone may be used as alternatives at 10-15 times physiological doses. 7
• Methylprednisolone 40-50 mg IV every 6 hours can substitute for hydrocortisone 200-300 mg/day in crisis situations. 8
• However, these alternatives lack mineralocorticoid activity, so aggressive IV saline resuscitation (1 L/hour initially) becomes even more critical. 4, 7