What is the management of adrenal insufficiency?

Management of Adrenal Insufficiency

All patients with confirmed adrenal insufficiency require lifelong glucocorticoid replacement therapy with hydrocortisone 15-25 mg daily in divided doses, and those with primary adrenal insufficiency additionally require mineralocorticoid replacement with fludrocortisone 0.05-0.2 mg daily. 1, 2, 3

Acute Management: Adrenal Crisis

For suspected adrenal crisis, immediately administer IV hydrocortisone 100 mg without waiting for diagnostic confirmation, as delay can be fatal. 1, 2

Emergency Protocol

• Give IV or IM hydrocortisone 100 mg immediately, followed by 100 mg every 6-8 hours (or 100-300 mg/day as continuous infusion) until the patient stabilizes 1, 2
• Simultaneously initiate aggressive IV fluid resuscitation with 3-4 liters of isotonic saline or 5% dextrose in isotonic saline at approximately 1 L/hour initially, with frequent hemodynamic monitoring to avoid fluid overload 1
• Monitor serum electrolytes closely and identify/treat the precipitating cause (infection, trauma, surgery, medication non-compliance) 1, 2
• Consider ICU admission depending on severity, along with gastric stress ulcer prophylaxis, low-dose heparin, and empiric antibiotics if infection is suspected 1
• Do not restart fludrocortisone until hydrocortisone dose decreases below 50 mg/day, as high-dose hydrocortisone provides sufficient mineralocorticoid activity 1

Chronic Maintenance Therapy

Primary Adrenal Insufficiency (Addison's Disease)

Patients require both glucocorticoid AND mineralocorticoid replacement. 1, 2, 3

• Glucocorticoid: Hydrocortisone 15-25 mg daily in split doses (typically two-thirds in morning, one-third in early afternoon to mimic physiologic cortisol rhythm) 1, 2, 3
• Mineralocorticoid: Fludrocortisone 50-200 μg as a single daily dose 2
• Monitor for adequate replacement by assessing normal blood pressure (postural hypotension indicates under-replacement), normal skin color (hyperpigmentation suggests under-replacement), stable weight, and serum sodium/potassium levels 1
• Titrate fludrocortisone to achieve normotension, normokalemia, and plasma renin activity in the upper normal range 1, 4

Secondary Adrenal Insufficiency

Patients require only glucocorticoid replacement, as mineralocorticoid function remains intact. 2, 3

• Hydrocortisone 10-20 mg in the morning and 5-10 mg in the afternoon 2
• No fludrocortisone is needed 2, 3

Alternative Glucocorticoid Options

• Prednisone 3-5 mg daily can be used instead of hydrocortisone 3
• Cortisone acetate is an alternative, though hydrocortisone remains the preferred agent 1

Stress-Dose Glucocorticoid Guidelines

All patients must increase their glucocorticoid dose during physiologic stress to prevent adrenal crisis. 2, 5, 3

Illness-Based Dosing

• Minor illness (fever, cold, minor infection): Double the usual daily dose 2
• Moderate illness (persistent vomiting, moderate fever, gastroenteritis): Triple the usual dose or use outpatient treatment at 2-3 times maintenance dose, tapering over 5-10 days as symptoms improve 1, 2
• Severe illness or trauma (high fever, severe infection, inability to take oral medications): IV hydrocortisone 100 mg immediately, followed by 100 mg every 6-8 hours 2, 3

Surgical Stress Dosing

• Administer IV hydrocortisone 100 mg before induction of anesthesia 1, 2
• Continue with 100 mg every 6-8 hours or as continuous infusion during and after the procedure 1, 2
• The specific dose and duration depend on surgical magnitude, but this approach applies to patients with known adrenal insufficiency or suspected adrenocortical reserve deficiency 1

Patient Education and Crisis Prevention

Comprehensive patient education is the most critical strategy to prevent life-threatening adrenal crisis. 1, 4

Essential Patient Instructions

• Teach patients and their partners how to self-administer IM hydrocortisone 100 mg for emergency use when oral intake is impossible 2, 3
• Prescribe injectable hydrocortisone for home emergency use 3
• Instruct patients to seek immediate medical attention if they develop vomiting, severe diarrhea, high fever, or are unable to take oral medications 1
• Provide medical alert bracelet or identification card indicating adrenal insufficiency 6, 2
• Emphasize that stress dosing must begin early during illness, before symptoms become severe 1, 4

Common Pitfalls to Avoid

• Never delay glucocorticoid administration while awaiting diagnostic confirmation in suspected adrenal crisis 2
• Do not start thyroid hormone replacement before or simultaneously with glucocorticoids in patients with both conditions, as this can precipitate adrenal crisis; always start glucocorticoids first 6
• Avoid chronic under-replacement with mineralocorticoids and inadequate salt intake, which are common causes of recurrent adrenal crises 1
• Recognize that patients on chronic glucocorticoid therapy (prednisolone ≥5 mg daily for ≥1 month via any route including oral, inhaled, topical, intranasal, or intra-articular) are at risk for hypothalamic-pituitary-adrenal axis suppression and may develop adrenal insufficiency 1

Annual Follow-Up and Monitoring

Regular medical examinations are essential to optimize replacement therapy and screen for associated conditions. 1

Clinical Assessment

• Evaluate overall health, well-being, weight stability, and blood pressure at each visit 1, 2
• Assess for signs of under-replacement (fatigue, weight loss, hyperpigmentation, postural hypotension) or over-replacement (weight gain, cushingoid features, hypertension) 1
• Review self-medication practices during intercurrent illnesses and any previous adrenal crises 1

Laboratory Monitoring

• Check serum sodium and potassium levels annually 1
• Serum and urine cortisol measurements are generally not useful for monitoring replacement adequacy 1
• If under-replacement is suspected, perform a morning cortisol absorption test (cortisol levels before and at 2,4, and 6 hours after the morning dose) to identify patients with rapid cortisol clearance who may benefit from more frequent dosing 1

Screening for Autoimmune Comorbidities

• Monitor thyroid function (TSH, free T4, TPO antibodies) every 12 months, as hypothyroidism and thyrotoxicosis frequently develop in autoimmune adrenal insufficiency 1
• Screen annually for diabetes mellitus (plasma glucose, HbA1c), pernicious anemia (complete blood count, vitamin B12), and celiac disease (tissue transglutaminase antibodies and total IgA if diarrhea is present) 1
• Inform women of reproductive age about the risk of premature ovarian insufficiency, especially if side-chain cleavage enzyme antibodies are present 1

Special Considerations

DHEA Supplementation

• Consider dehydroepiandrosterone (DHEA) 25-50 mg daily in women with primary adrenal insufficiency who have persistent fatigue, impaired well-being, or reduced libido despite adequate glucocorticoid and mineralocorticoid replacement 4
• While not yet FDA-approved for this indication, multiple studies demonstrate improvement in mood, fatigue, and sexual function 4

Glucocorticoid-Induced Adrenal Insufficiency

• This is the most common form of adrenal insufficiency encountered in clinical practice 1, 3
• Suspect in any patient who has recently tapered or discontinued supraphysiological glucocorticoid doses 3
• HPA axis suppression may persist for months after discontinuation of chronic glucocorticoid therapy, requiring stress-dose coverage during this period 5, 7