What is the inpatient treatment for stable adrenal insufficiency (Addison's disease)?

From the Guidelines

Inpatient treatment of stable adrenal insufficiency requires prompt administration of glucocorticoid replacement therapy, typically with hydrocortisone 100 mg intravenously at the start of surgery, followed by an infusion of 200 mg/24h. This approach is based on the most recent guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1. For patients who are able to take oral medications, doubling the regular oral replacement dose of hydrocortisone for 48 hours, and for up to a week following major surgery, is recommended before resuming the maintenance dose 1.

Key Considerations

• Mineralocorticoid replacement with fludrocortisone 0.05-0.2 mg daily is necessary for primary adrenal insufficiency but not required when using high-dose hydrocortisone or for secondary adrenal insufficiency 1.
• Fluid and electrolyte status should be closely monitored, with correction of any hyponatremia, hyperkalemia, or hypoglycemia 1.
• Regular vital sign checks are essential, particularly blood pressure monitoring to detect orthostatic hypotension 1.
• Patient education regarding stress dosing and the need for medical alert identification is crucial before discharge to prevent future adrenal crises 1.

Pathophysiology and Clinical Context

The underlying pathophysiology involves insufficient cortisol production, which is essential for stress response, glucose metabolism, and maintaining vascular tone, while aldosterone deficiency in primary adrenal insufficiency leads to sodium loss and potassium retention 1. Patients with comorbidities, such as asthma and diabetes, are more vulnerable to adrenal crisis 1.

Recommendations for Practice

• Hydrocortisone 100 mg by intravenous injection should be given at induction of anesthesia in adult patients with adrenal insufficiency from any cause, followed by a continuous infusion of hydrocortisone at 200 mg/24h until the patient can take double their usual oral glucocorticoid dose by mouth 1.
• Dexamethasone is not adequate as glucocorticoid treatment in patients with primary adrenal insufficiency as it has no mineralocorticoid activity 1.
• Children with adrenal insufficiency are more vulnerable to problems with glycemic control than adults and require frequent blood glucose monitoring 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity Thus, if constantly high blood levels are required, injections should be made every 4 to 6 hours

The inpatient treatment of stable adrenal insufficiency can be managed with hydrocortisone (IV), which is used as replacement therapy in adrenocortical deficiency states.

• The dosing interval for hydrocortisone (IV) is every 4 to 6 hours if constantly high blood levels are required 2.
• Hydrocortisone has metabolic and anti-inflammatory actions and is particularly useful where high blood levels are required rapidly.

From the Research

Inpatient Treatment of Stable Adrenal Insufficiency

• The treatment of adrenal insufficiency typically involves glucocorticoid replacement therapy, with hydrocortisone being the most commonly used medication 3, 4, 5, 6, 7.
• The recommended dose of hydrocortisone is 15-25 mg/day, divided into two or three separate doses 3, 4, 7.
• Patients with primary adrenal insufficiency also require mineralocorticoid replacement, typically with fludrocortisone 0.05-0.2 mg/day 3, 4, 7.
• Dehydroepiandrosterone (DHEA) replacement may also be considered, as it has been shown to improve mood, fatigue, and well-being in some patients 3, 6, 7.
• It is essential to monitor patients closely and adjust the dose of replacement therapy as needed to prevent over- or under-replacement 5, 6.
• Educational programs for patients with adrenal insufficiency are crucial to prevent acute adrenal insufficiency, a life-threatening complication of glucocorticoid and mineralocorticoid under-replacement 6.

Management of Adrenal Insufficiency in Different Clinical Settings

• Adrenal insufficiency can be primary or secondary, with different causes and treatment approaches 3, 4.
• Patients with adrenal insufficiency are at risk of adrenal crisis, usually precipitated by major stress, such as severe infection or surgery 3, 4.
• Early dose adjustments are required to cover the increased glucocorticoid demand in stress 3, 4.
• The treatment of adrenal insufficiency should be individualized, taking into account the patient's specific needs and circumstances 5, 6, 7.

Future Directions in the Treatment of Adrenal Insufficiency

• New slow-release hydrocortisone formulations may help reproduce a more physiological cortisol plasma profile and reduce the impact of over-replacement on cardiovascular risk factors and glucose metabolism 6.
• Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities 7.
• Further research is needed to determine the optimal treatment approach for adrenal insufficiency and to improve patient outcomes 5, 6, 7.