What is the recommended glucocorticoid (hydrocortisone) maintenance dose and stress‑dosing protocol, plus mineralocorticoid (fludrocortisone) replacement, for an adult with primary adrenal insufficiency?

Steroid Dosing in Primary Adrenal Insufficiency

Glucocorticoid Maintenance Therapy

For adults with primary adrenal insufficiency, hydrocortisone 15-25 mg daily divided into 2-3 doses is the preferred glucocorticoid replacement, with the first dose taken immediately upon awakening and the last dose at least 6 hours before bedtime. 1

Standard Hydrocortisone Regimens

Three-dose regimen (preferred for most patients):

• 10 mg at 07:00 + 5 mg at 12:00 + 2.5-5 mg at 16:00 1
• Alternative options: 15 mg + 5 mg + 5 mg, or 10 mg + 5 mg + 5 mg, or 7.5 mg + 5 mg + 2.5 mg 1

Two-dose regimen (for compliance or long work shifts):

• 15 mg at 07:00 + 5 mg at 12:00, or 10 mg + 10 mg, or 10 mg + 5 mg 1

The three-dose regimen better mimics physiologic cortisol secretion, though no studies definitively prove superiority of one regimen over another 1. The key principle is that individuals with normal adrenal function produce 5-10 mg cortisol per m² body surface area daily, equivalent to 15-25 mg oral hydrocortisone 1.

Alternative Glucocorticoids (Second-Line)

Cortisone acetate: 25-37.5 mg daily in divided doses (requires hepatic conversion to hydrocortisone) 1

Prednisolone: 4-5 mg daily should only be considered when hydrocortisone/cortisone acetate is not tolerated or when compliance problems exist 1, 2. Typical regimens are 4-5 mg upon awakening as a single dose, or 3 mg at awakening + 1-2 mg at 14:00 1, 2. Dexamethasone should be avoided due to non-physiologic, prolonged suppression and increased risk of iatrogenic Cushing's syndrome 1, 3.

Mineralocorticoid Replacement (Essential in Primary Adrenal Insufficiency)

All patients with primary adrenal insufficiency require fludrocortisone 50-200 µg daily as a single morning dose. 1, 4, 5

Fludrocortisone Dosing Details

• Standard adult dose: 100 µg (0.1 mg) daily 4
• Dose range: 50-200 µg daily for most adults 1, 6
• 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 1
• Taken as a single dose upon awakening 1

Critical Monitoring for Fludrocortisone Adequacy

Clinical assessment includes:

• Blood pressure in supine and standing positions (orthostatic hypotension suggests under-replacement) 1, 7
• Salt cravings or lightheadedness 1
• Peripheral edema (suggests over-replacement) 1

Laboratory monitoring:

• Serum sodium and potassium 7
• Plasma renin activity (target upper half of reference range) 7

Common Pitfall: Mineralocorticoid Under-Replacement

Under-replacement of fludrocortisone is common and dangerous. 1, 3 Patients and clinicians often compensate by over-replacing glucocorticoids, which predisposes to recurrent adrenal crises while causing long-term glucocorticoid excess complications 1, 2. If essential hypertension develops, reduce but never stop fludrocortisone; instead add a vasodilator 1.

Stress-Dosing Protocol

During minor illness (fever, gastroenteritis, significant physical stress): Double or triple the hydrocortisone dose 7, 3, 5

During severe illness, vomiting, or inability to take oral medications: Administer hydrocortisone 100 mg intramuscularly immediately, then 100 mg every 6-8 hours until recovered 1, 5. Simultaneously infuse 0.9% sodium chloride at 1 L/hour initially until hemodynamic improvement 1.

All patients must carry emergency injectable hydrocortisone supplies and know how to self-administer 1, 7, 5.

Drug and Food Interactions Requiring Dose Adjustment

Medications That Increase Hydrocortisone Requirements:

• Anti-epileptics/barbiturates 1, 2
• Antituberculosis drugs (rifampin) 1, 3
• Etomidate 1
• Topiramate 1

Substances That Decrease Requirements:

• Grapefruit juice 1, 2, 3
• Liquorice 1, 2

Medications to Avoid with Fludrocortisone:

• Diuretics 1, 7
• Acetazolamide 1, 7
• NSAIDs 1, 7
• Carbenoxolone, liquorice 1

Drospirenone-containing contraceptives may require increased fludrocortisone doses 1.

Monitoring Glucocorticoid Replacement Adequacy

Plasma ACTH and serum cortisol are NOT useful for dose adjustment. 1 Monitoring relies primarily on clinical assessment 1, 3.

Signs of Over-Replacement:

• Weight gain 1
• Insomnia 1
• Peripheral edema 1

Signs of Under-Replacement:

• Lethargy, nausea, poor appetite 1
• Weight loss 1
• Increased or uneven pigmentation 1

Fine-tuning involves detailed questioning about energy levels throughout the day, mental concentration, daytime somnolence, and ease of falling asleep 1.

Special Situations

Morning nausea/lack of appetite: Wake earlier to take the first hydrocortisone dose, then return to sleep 1, 2

Night shift workers: Adjust dosing to sleep-wake pattern (e.g., 10 mg upon awakening before work) 1, 2

Pregnancy: May require small adjustments to both hydrocortisone and fludrocortisone, particularly in the last trimester; parenteral hydrocortisone should be given during delivery 1

Essential Patient Education

• Wear Medic Alert identification jewelry 1
• Carry a steroid emergency card 1
• Unrestricted sodium intake; avoid potassium-containing salt substitutes 1, 3
• Annual review with assessment of weight, blood pressure, and serum electrolytes 1, 7