What is the management and treatment approach for adrenal insufficiency?

From the Guidelines

The management of adrenal insufficiency should prioritize hormone replacement therapy with hydrocortisone 15-25 mg daily, divided into 2-3 doses, to mimic the natural cortisol rhythm, as recommended by the most recent guidelines 1. The cornerstone of treatment is glucocorticoid replacement, with hydrocortisone being the preferred option due to its shorter half-life and more physiologic profile.

• For primary adrenal insufficiency (Addison's disease), mineralocorticoid replacement with fludrocortisone 0.05-0.2 mg once daily is also necessary to maintain sodium and potassium balance.
• Patients must be educated about stress dosing—typically doubling or tripling their glucocorticoid dose during illness, significant physical stress, or surgery—to prevent adrenal crisis.
• All patients should carry a steroid emergency card and wear medical identification, and must have access to an emergency injection kit containing hydrocortisone 100 mg for intramuscular administration during severe illness or if unable to take oral medication. Some key points to consider in the management of adrenal insufficiency include:
• Regular monitoring of clinical assessment of symptoms, blood pressure, electrolytes, and plasma renin activity to ensure optimal replacement.
• Treatment is lifelong, and patients require ongoing education about their condition to manage it effectively and prevent potentially life-threatening adrenal crises.
• The use of dexamethasone is not recommended for primary adrenal insufficiency due to its lack of mineralocorticoid activity 1.
• In cases of suspected adrenal insufficiency, emergent therapy with hydrocortisone 100 mg is recommended, and endocrine consultation prior to surgery or any procedure for stress-dose planning is necessary 1.

From the FDA Drug Label

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance) Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used)

The management and treatment approach for adrenal insufficiency involves the use of hydrocortisone or cortisone as the drug of choice.

• Synthetic analogs may be used in conjunction with mineralocorticoids where applicable.
• In infancy, mineralocorticoid supplementation is of particular importance.
• Acute adrenocortical insufficiency requires hydrocortisone or cortisone as the drug of choice, with mineralocorticoid supplementation necessary in some cases, particularly when synthetic analogs are used 2.

From the Research

Management of Adrenal Insufficiency

The management of adrenal insufficiency involves replacing the deficient hormones with medication. The goal is to mimic the natural production of cortisol and aldosterone as closely as possible.

• Glucocorticoid replacement therapy is the mainstay of treatment, with hydrocortisone being the most commonly used medication 3, 4, 5.
• The dosage and administration of hydrocortisone vary depending on the individual patient's needs and the severity of their condition.
• Some studies suggest that modified-release hydrocortisone preparations may be more effective in mimicking the natural circadian rhythm of cortisol secretion than conventional twice or thrice daily treatment 4.

Treatment Approach

The treatment approach for adrenal insufficiency typically involves:

• Chronic glucocorticoid replacement with hydrocortisone 15-25 mg/day in divided doses 6.
• Mineralocorticoid replacement with fludrocortisone 0.05-0.2 mg/day to control blood pressure and electrolyte levels 6.
• Dehydroepiandrosterone (DHEA) replacement may be considered in some cases to improve mood, fatigue, and well-being 6.
• Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis 3.

Pharmacokinetic Evidence

Pharmacokinetic studies have shown that currently available hydrocortisone tablets may not provide optimal treatment for adrenal insufficiency 7.

• A study found that 79%, 55%, and 45% of patients were over- or under-treated at 0800,1600, and 2400 h, respectively, when using conventional hydrocortisone replacement regimens 7.
• Simulation of different dosing regimens suggested that a regimen of 10 + 5 + 5 mg at 0730,1200, and 1630 h, respectively, may be more effective in achieving physiological target concentrations, but individualized dose adjustment would be more accurate 7.

Adrenal Crisis Prevention

Prevention of adrenal crisis is crucial in the management of adrenal insufficiency.

• Continuous intravenous hydrocortisone infusion may be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress 3.
• Early dose adjustments are required to cover the increased glucocorticoid demand in stress, and careful education of patients and their partners is essential to avoid this life-threatening emergency 6.