Adrenal Insufficiency Management

Diagnosis and Treatment

The American College of Physicians recommends considering adrenal insufficiency in patients with unexplained collapse, hypotension, vomiting, diarrhea, hyperpigmentation, hyponatremia, hyperkalaemia, acidosis, or hypoglycemia 1, 2
Diagnostic workup for adrenal insufficiency includes morning ACTH and cortisol levels, with primary AI characterized by low cortisol and high ACTH, and secondary AI characterized by low cortisol and low ACTH 3, 4
The Endocrine Society recommends an ACTH stimulation test for equivocal cases, with a peak cortisol level <500 nmol/L being diagnostic 1, 2
Immediate treatment of suspected acute adrenal insufficiency should not be delayed for diagnostic procedures, with the American College of Emergency Physicians recommending immediate IV or IM hydrocortisone 100 mg 1, 2

Treatment Algorithm by Severity

For adrenal crisis, the American College of Emergency Physicians recommends immediate IV or IM hydrocortisone 100 mg, followed by 100 mg every 6-8 hours until recovered, along with IV isotonic sodium chloride solution and identification and treatment of underlying precipitants 1, 2
For moderate symptoms, the American College of Physicians recommends outpatient treatment at 2-3 times maintenance dose, with tapering to maintenance doses over 5-10 days 3, 5
For mild symptoms or maintenance therapy, primary adrenal insufficiency requires both glucocorticoid and mineralocorticoid replacement, while secondary adrenal insufficiency requires only glucocorticoid replacement 3, 1

Special Considerations

The Endocrine Society recommends that patients with primary adrenal insufficiency receive hydrocortisone 15-25 mg daily in split doses and fludrocortisone 50-200 μg as a single daily dose 1, 2
Patients with secondary adrenal insufficiency should receive hydrocortisone 10-20 mg morning and 5-10 mg afternoon, without fludrocortisone 4, 6
The American College of Physicians recommends annual follow-up with assessment of health and well-being, weight and blood pressure, serum electrolytes, and development of new autoimmune disorders 1, 2

Stress Dosing Guidelines

The American College of Physicians recommends doubling the usual daily dose for minor illness, tripling the dose for moderate illness, and using IV hydrocortisone for severe illness or trauma 1, 2, 6
For surgery, IV hydrocortisone 100 mg should be administered before induction, followed by continuous infusion or divided doses during and after the procedure 1, 2

Steroid Dosing in Adrenal Insufficiency

Maintenance and Stress Dosing

The American College of Physicians recommends hydrocortisone 100 mg IV or IM bolus immediately for severe illness, trauma, or adrenal crisis, followed by hydrocortisone 100 mg IV every 6-8 hours 7
The Endocrine Society suggests that during moderate illness, the usual daily dose of hydrocortisone should be tripled or 2-3 times the maintenance dose 7

Perioperative Steroid Coverage

The American Society of Anesthesiologists recommends intraoperative hydrocortisone 100 mg IV at induction, followed by continuous infusion of 200 mg/24h for major surgery 8 9
The American College of Surgeons advises to continue hydrocortisone 200 mg/24h IV infusion postoperatively while nil by mouth, and to transition to oral double the usual dose for 48 hours after uncomplicated recovery 8 9

Patient Education and Special Considerations

The National Adrenal Diseases Foundation emphasizes that all patients with adrenal insufficiency must have a medical alert bracelet and explicit stress-dosing instructions, including emergency injectable hydrocortisone at home 7
The American Academy of Clinical Endocrinologists recommends endocrine consultation before any surgery for stress-dose planning 7
The European Society of Endocrinology suggests that patients on chronic exogenous steroids receiving prednisolone equivalent ≥5 mg for ≥4 weeks require perioperative coverage as outlined above 8 9

Corticosteroid Regimen for Adrenal Insufficiency

Maintenance Therapy

The Endocrine Society recommends hydrocortisone 15-25 mg daily in divided doses for primary adrenal insufficiency, and hydrocortisone alone without mineralocorticoid replacement for secondary adrenal insufficiency 10, 11
Hydrocortisone is the preferred glucocorticoid because it allows recreation of the diurnal cortisol rhythm and has a short half-life 10

Glucocorticoid Replacement

The standard equivalency is: 20 mg hydrocortisone = 5 mg prednisone 10
Long-acting steroids like prednisone carry risk of over-replacement but can be used if adherence to short-acting regimens is problematic 10

Mineralocorticoid Replacement

Fludrocortisone 0.05-0.1 mg daily as a single morning dose is recommended for patients with primary adrenal insufficiency 10, 11
Titrate based on volume status, serum sodium, potassium, and renin levels (target upper half of reference range) 10

Stress Dosing for Illness

Double the usual daily hydrocortisone dose until recovery, and continue doubled dose for 24-48 hours after symptoms resolve 11
Triple the usual daily dose or use 2-3 times maintenance for moderate illness (e.g., hydrocortisone 30-50 mg total daily or prednisone 20 mg daily) 10
Immediate IV or IM hydrocortisone 100 mg bolus without delay for diagnostic testing is recommended for severe illness or adrenal crisis 11

Perioperative Management

Hydrocortisone 100 mg IV at induction, followed immediately by continuous infusion of 200 mg/24 hours, is recommended for major surgery 12, 13
Double oral dose for 48 hours after delivery, and educate patients on stress dosing and emergency injectable hydrocortisone 11

Critical Patient Education Requirements

All patients must receive education on stress dosing, possess emergency injectable hydrocortisone at home, and wear a medical alert bracelet or necklace 10, 11
Recognition of adrenal crisis symptoms: severe weakness, confusion, abdominal pain, vomiting, hypotension 11

Common Pitfalls to Avoid

Never use dexamethasone for long-term replacement in primary adrenal insufficiency as it lacks mineralocorticoid activity 14
Do not delay treatment of suspected adrenal crisis for diagnostic testing—draw blood for cortisol and ACTH, then treat immediately 11
Do not initiate thyroid hormone replacement before adrenal replacement in hypopituitarism, as this can precipitate adrenal crisis 10
Patients on chronic steroids (prednisolone ≥5 mg for ≥4 weeks) require perioperative stress dosing even without diagnosed adrenal insufficiency 12, 14

Hydrocortisone Dosing Recommendations for Adrenal Insufficiency

Maintenance and Stress Dosing

For children with adrenal insufficiency, weight-based dosing of hydrocortisone is essential, with 2 mg/kg administered every 4-6 hours depending on clinical stability, as recommended by the Anaesthesia society 15, 16
In cases of severe illness or adrenal crisis, immediate hydrocortisone 100 mg IV or IM bolus is recommended, followed by hydrocortisone 100 mg IV every 6-8 hours or continuous infusion of 200-300 mg/24 hours, according to the Journal of Internal Medicine society 17

Perioperative Management

For adults undergoing major surgery, hydrocortisone 100 mg IV bolus at induction, followed by continuous infusion of 200 mg/24 hours, is recommended by the Anaesthesia society 15
For children undergoing major surgery, hydrocortisone 2 mg/kg IV at induction, followed by weight-based continuous infusion, is recommended by the Anaesthesia society 15, 16
For patients on chronic corticosteroids, perioperative stress dosing identical to those with diagnosed adrenal insufficiency is required, as recommended by the Anaesthesia society 15

Special Considerations

Patients on chronic inhaled corticosteroids at high doses may have HPA axis suppression and require stress dosing consideration, as noted by the Anaesthesia society 15, 16
In labor and delivery, hydrocortisone 100 mg IV at onset of labor, followed by continuous infusion of 200 mg/24 hours, is recommended by the Anaesthesia society 15, 16

Stress‑Dose Hydrocortisone Regimens for Adrenal Insufficiency

Severe Stress (Adrenal Crisis, Major Surgery, Sepsis)

Immediate 100 mg IV/IM bolus followed by a continuous infusion of 200 mg hydrocortisone over 24 h provides superior maintenance of physiologic cortisol concentrations compared with intermittent bolus dosing during major stress. 18, 19
Continuous infusion is the only administration mode that consistently achieves median cortisol levels observed in major stress, ensuring more stable hormone exposure. 18, 19
Stress dosing should be continued until the patient is clinically stable and recovering, after which therapy can be transitioned to an oral dose that is doubled relative to the usual maintenance regimen. 18, 19, 20

Mild Stress (Minor Illness, Fever, Dental Procedures)

Double the usual daily maintenance dose of hydrocortisone (e.g., a typical regimen of 10 mg‑5 mg‑5 mg becomes 20 mg‑10 mg‑10 mg) for the duration of the stressor. 18, 19, 20

Peri‑operative Stress Dosing

Major Surgery

Induction: Administer a 100 mg IV hydrocortisone bolus at the start of surgery. 18, 19, 20
Intra‑ and postoperative period: Maintain a continuous IV infusion of 200 mg hydrocortisone over the subsequent 24 h. 18, 19
Recovery phase (uncomplicated): After surgery, give an oral hydrocortisone dose that is twice the regular maintenance amount for 48 h to 1 week before returning to the baseline regimen. 18, 19, 20
Prolonged critical illness: Continue the stress‑dose IV infusion until the patient reaches clinical stability and begins recovery. 18, 19, 20

Dexamethasone as an Alternative Agent

Equivalency: A single dose of 8 mg dexamethasone provides glucocorticoid activity comparable to approximately 200 mg hydrocortisone. 21
Duration of action: Because of its long‑acting properties, dexamethasone supplies adequate glucocorticoid coverage for roughly 24 h. 21
Limitation: Dexamethasone lacks mineralocorticoid activity and is therefore inadequate as the sole agent for stress dosing in primary adrenal insufficiency; it should not be used alone in this setting. 21
Drug‑interaction consideration: Patients receiving CYP3A4‑inducing medications (e.g., certain anticonvulsants, rifampin) may need higher glucocorticoid doses due to accelerated cortisol clearance. 21

Critical Pitfalls to Avoid

Do not delay treatment of a suspected adrenal crisis for diagnostic testing; postponement markedly increases mortality. 18, 19
Avoid intermittent bolus dosing when a continuous infusion is feasible, because bolus regimens produce peaks and troughs that result in suboptimal cortisol profiles. 18, 19
Never use dexamethasone alone for stress dosing in primary adrenal insufficiency because of its lack of mineralocorticoid activity. 21
Prevent medication errors and omissions on hospital wards, as these are documented contributors to adrenal crises; ensure uninterrupted stress‑dose administration. 18, 19

Cephalexin Use and Glucocorticoid Stress‑Dosing in Children with Primary Adrenal Insufficiency

Antibiotic Safety

Cephalexin can be used safely for skin infections in pediatric patients with primary adrenal insufficiency, provided that stress‑dose glucocorticoid supplementation is instituted to avert adrenal crisis. 22

Glucocorticoid Stress‑Dose Management

For severe physiological stress (e.g., infection, fever, vomiting) in children with adrenal insufficiency, a weight‑based hydrocortisone regimen of 2 mg/kg IV every 4–6 hours may be employed as an alternative to the standard 100 mg IV/IM bolus; however, the 100 mg bolus remains the recommended initial dose even in the pediatric population. 22

Monitoring During Treatment

During infection‑related stress, blood glucose levels should be checked in children with adrenal insufficiency who appear unwell, because hypoglycemia may signal inadequate glucocorticoid coverage. 22