What is the standard dosing regimen for Hisone (hydrocortisone) replacement in adult patients with adrenal insufficiency?

Standard Dosing Regimen for Hisone (Hydrocortisone) in Adult Adrenal Insufficiency

The standard replacement regimen for adult patients with adrenal insufficiency is hydrocortisone 15-25 mg daily divided into 2-3 doses, with the majority of the dose given in the morning to mimic physiological cortisol rhythm. 1, 2

Glucocorticoid Replacement Dosing

Standard Daily Dosing Regimens

The most commonly recommended hydrocortisone dosing schedule is a three-dose regimen:

• 10 mg upon waking (07:00 ± 1 hour)
• 5 mg at midday (12:00 ± 1 hour)
• 2.5-5 mg in late afternoon (16:00 ± 1 hour) 1, 2

Alternative three-dose regimens that fall within the 15-25 mg daily range include:

• 15 mg + 5 mg + 5 mg 1
• 10 mg + 5 mg + 5 mg 1
• 10 mg + 5 mg + 2.5 mg 1
• 7.5 mg + 5 mg + 2.5 mg 1

For patients requiring a two-dose regimen (such as those with compliance issues or specific work schedules), options include:

• 15 mg + 5 mg 1
• 10 mg + 10 mg 1
• 10 mg + 5 mg 1

The rationale for divided dosing is that immediate-release hydrocortisone cannot provide physiological cortisol rhythm, and conventional twice- or thrice-daily fixed doses inevitably result in temporary over- or under-replacement throughout the day. 3, 4

Dosing Principles

Two-thirds of the total daily dose should be given in the morning and one-third in the early afternoon to recreate the diurnal rhythm of cortisol. 1 This mimics the physiological pattern where cortisol levels are highest in the morning and decline throughout the day.

The FDA label indicates that initial dosage may vary from 20-240 mg daily depending on disease severity, but for chronic replacement therapy in adrenal insufficiency, the 15-25 mg range is appropriate. 5

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Patients with primary adrenal insufficiency (Addison's disease) require fludrocortisone 50-200 μg (0.05-0.2 mg) once daily, typically taken upon awakening. 1, 2 Secondary adrenal insufficiency does not require mineralocorticoid replacement as the renin-angiotensin-aldosterone system remains intact.

Higher fludrocortisone doses up to 500 μg daily may be needed in:

• Children and younger adults 1, 2
• Last trimester of pregnancy (when progesterone counteracts mineralocorticoids) 1

Adequacy of mineralocorticoid replacement is assessed by:

• Absence of salt craving 1
• Blood pressure in supine and standing positions (no orthostatic hypotension) 1
• Absence of peripheral edema 1, 2
• Serum electrolytes (normal sodium and potassium) 1, 2
• Plasma renin activity in the upper half of the reference range 1

Important Clinical Considerations

Common Pitfall: Under-replacement with Mineralocorticoids

Under-replacement with fludrocortisone is common and sometimes compensated for by over-replacement with glucocorticoids, which predisposes patients to recurrent adrenal crises. 1, 2 This is a critical error to avoid, as inadequate mineralocorticoid replacement can lead to persistent hypotension, hyponatremia, and increased risk of life-threatening adrenal crisis.

Sodium Intake

Patients should be advised to eat sodium salt and salty foods without restriction and to avoid potassium-containing salts. 1, 2 Unrestricted sodium intake is an important third component of replacement therapy alongside glucocorticoid and mineralocorticoid replacement.

Drug Interactions Requiring Dose Adjustment

Medications that may increase hydrocortisone requirements include:

• Anti-epileptics/barbiturates 1, 2
• Antituberculosis medications 1, 2
• Etomidate 1, 2
• Topiramate 1, 2

Substances that may decrease hydrocortisone requirements include:

• Grapefruit juice 1, 2
• Licorice 1, 2

Medications to avoid with fludrocortisone:

• Diuretics 1
• Acetazolamide 1
• NSAIDs 1, 2
• Carbenoxolone and licorice 1

Drospirenone-containing contraceptives may increase fludrocortisone requirements. 1

Hypertension Management

If essential hypertension develops in a patient with primary adrenal insufficiency, add a vasodilator rather than stopping mineralocorticoid replacement, though a dose reduction of fludrocortisone should be considered. 1, 2

Alternative Glucocorticoid Options

Cortisone acetate can be used as an alternative at 25-37.5 mg daily in divided doses (typically 12.5 mg + 6.25 mg + 6.25 mg or similar regimens). 1

Prednisolone (4-5 mg daily) should only be considered when:

• Compliance problems exist 1, 2
• Marked fluctuations of energy occur 1, 2
• Hydrocortisone/cortisone acetate is not tolerated 1, 2

The equivalence is 20 mg hydrocortisone = 5 mg prednisolone. 1, 5 Long-acting steroids like prednisolone carry risk of over-replacement as they cannot recreate diurnal cortisol rhythm. 1

Stress Dosing Requirements

During minor illness (fever, infection), patients should double or triple their usual hydrocortisone dose. 2 For moderate stress (grade 2 symptoms), hydrocortisone 30-50 mg total daily dose or prednisone 20 mg daily may be used initially, then decreased to maintenance after 2 days. 1

For severe stress, surgery, or adrenal crisis, intravenous hydrocortisone 100 mg is required immediately, followed by 50-100 mg every 6-8 hours. 1, 2, 6