What steroid is recommended for adrenal failure?

Steroid Selection for Adrenal Failure

Hydrocortisone is the steroid of choice for treating adrenal insufficiency, given as 15-25 mg daily in divided doses for chronic replacement, or 100 mg IV bolus followed by 100-300 mg/day for acute adrenal crisis. 1

Acute Adrenal Crisis (Life-Threatening Emergency)

Immediate treatment must not be delayed by diagnostic procedures. 1

First-Line Emergency Protocol

• Hydrocortisone 100 mg IV bolus immediately upon recognition of crisis 1
• Follow with 100-300 mg/day as continuous IV infusion OR 50 mg IV/IM every 6 hours 1
• Simultaneously administer 1 L isotonic saline over first hour, then 3-4 L total over 24-48 hours 1
• The high-dose hydrocortisone saturates 11β-HSD type 2 enzyme, providing essential mineralocorticoid effect in addition to glucocorticoid replacement 1

Tapering Strategy

• Continue parenteral hydrocortisone for 24-48 hours 1
• Taper over 1-3 days to oral dosing if precipitating illness permits 1
• Resume fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Critical Caveat About Dexamethasone

Dexamethasone is inadequate for primary adrenal insufficiency because it lacks mineralocorticoid activity, though it may be used in secondary adrenal insufficiency (6-8 mg IV provides 24-hour coverage equivalent to 200 mg hydrocortisone) 1, 2

Chronic Maintenance Therapy

Glucocorticoid Replacement (Primary Choice)

Hydrocortisone 15-25 mg/day in divided doses is the preferred glucocorticoid because it is structurally identical to endogenous cortisol 1, 3

Optimal dosing regimens: 1

• Three-dose schedule: 10 mg at 0700h + 5 mg at 1200h + 2.5-5 mg at 1600h
• Two-dose schedule: 15 mg at 0700h + 5 mg at 1200h (for simplified compliance)
• Doses should be taken approximately 1 hour before the stated times to match physiological cortisol rhythm 1

Alternative Glucocorticoid: Cortisone Acetate

• Cortisone acetate 25-37.5 mg/day in divided doses (requires hepatic conversion to cortisol) 1
• Typical regimen: 12.5 mg + 6.25 mg + 6.25 mg at same time intervals as hydrocortisone 1

Prednisolone (Limited Role)

Prednisolone should only be considered for select patients with compliance problems or marked energy fluctuations when hydrocortisone/cortisone acetate is not tolerated 1

• Dose: 4-5 mg once daily at 0700h, or 3 mg at 0700h + 1-2 mg at 1400h 1
• Equivalency: 10 mg hydrocortisone = 2 mg prednisolone 1, 4

Primary vs. Secondary Adrenal Insufficiency: Critical Distinction

Primary Adrenal Insufficiency (Addison's Disease)

Requires BOTH glucocorticoid AND mineralocorticoid replacement because the entire adrenal cortex is destroyed 5, 3

Mineralocorticoid component: 1, 5

• Fludrocortisone 50-200 mcg (0.05-0.2 mg) once daily upon awakening
• Higher doses up to 500 mcg may be needed in children, young adults, or third trimester pregnancy 1, 5
• Monitor with blood pressure (supine and standing), plasma renin activity (target upper normal range), and serum electrolytes 1, 5

Secondary Adrenal Insufficiency

Requires only glucocorticoid replacement (mineralocorticoid function preserved via intact renin-angiotensin system) 3

Perioperative/Surgical Stress Dosing

Major Surgery Protocol

Hydrocortisone 100 mg IV at induction, followed immediately by continuous infusion of 200 mg/24 hours 1, 2

• Alternative: Hydrocortisone 50 mg IV/IM every 6 hours 1
• Continue IV dosing while nil-by-mouth or vomiting 1
• Double oral maintenance dose for 48 hours after resuming enteral intake for uncomplicated recovery 1, 4
• Continue doubled doses up to one week for major/complicated surgery before tapering 1, 4

Labor and Vaginal Delivery

Hydrocortisone 100 mg IV/IM at onset of labor, then either: 1

• Continuous infusion 200 mg/24 hours, OR
• 50 mg IM every 6 hours until delivery
• Double oral dose for 24-48 hours postpartum 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Under-Replacement of Mineralocorticoids

Chronic mineralocorticoid under-replacement predisposes to recurrent adrenal crises and is often compensated by inappropriate glucocorticoid over-replacement 5

• Solution: Measure plasma renin activity (aim for upper normal range) and assess for postural hypotension 1, 5

Pitfall 2: Failure to Increase Doses During Illness

Patients must double or triple glucocorticoid doses during febrile illness, vomiting, or stress to prevent adrenal crisis 1, 6, 7

• Solution: All patients should carry injectable hydrocortisone 100 mg for emergency self-administration 3

Pitfall 3: Using Dexamethasone in Primary Adrenal Insufficiency

Dexamethasone provides no mineralocorticoid activity and will not prevent crisis in primary adrenal insufficiency 1, 2

• Solution: Always use hydrocortisone for primary adrenal insufficiency; dexamethasone acceptable only for secondary adrenal insufficiency 1, 2

Pitfall 4: Inadequate Patient Education

Adrenal crises occur at 6-8 per 100 patient-years, with mortality risk ratio of 2.19 for men and 2.86 for women 4, 3

• Solution: Repeated education on stress dosing, emergency injection technique, and medical alert identification 1, 7

Drug Interactions Requiring Dose Adjustment

Medications that increase hydrocortisone requirements: 1

• Anti-epileptics/barbiturates
• Antituberculosis drugs (rifampin)
• Topiramate
• Etomidate

Medications that decrease hydrocortisone requirements: 1

• Antifungal drugs (azoles)
• Grapefruit juice
• Licorice

FDA-Approved Indication

Hydrocortisone IV (Solu-Cortef) is FDA-approved for primary or secondary adrenocortical insufficiency, with the label stating "hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable" 8