Hydrocortisone: Clinical Applications and Dosing
Maintenance Therapy for Adrenal Insufficiency
For chronic replacement in primary adrenal insufficiency, prescribe hydrocortisone 15-20 mg daily in divided doses (typically two-thirds in the morning, one-third in early afternoon) to mimic physiological diurnal cortisol rhythm. 1, 2
- Hydrocortisone is structurally identical to cortisol and preferred over long-acting steroids like prednisone for replacement therapy because it allows recreation of the natural diurnal pattern 1
- Equivalency: 20 mg hydrocortisone = 5 mg prednisone = 0.75 mg dexamethasone 1
- Patients with primary adrenal insufficiency require concurrent fludrocortisone (0.05-0.1 mg daily) for mineralocorticoid replacement 1, 2
- Monitor for over-replacement (bruising, thin skin, edema, weight gain, hypertension, hyperglycemia) and under-replacement (fatigue, nausea, hypotension, electrolyte abnormalities) 2
Stress Dosing and Perioperative Management
Major Surgery or Critical Illness
Administer hydrocortisone 100 mg IV bolus at induction, followed by continuous IV infusion of 200 mg over 24 hours. 1, 2, 3
- Continuous IV infusion is superior to intermittent bolus dosing for maintaining stable plasma cortisol concentrations in the range observed during major physiological stress 1, 3
- This approach was validated by pharmacokinetic modeling showing that continuous infusion preceded by a 50-100 mg bolus best maintains therapeutic cortisol levels during major stress 3
- If IV access is impractical, hydrocortisone 50 mg IM every 6 hours is an acceptable alternative with a long tradition of safety and clinical effectiveness 1, 4
Intermediate Surgery
Give hydrocortisone 100 mg IV at induction with subsequent dose adjustments based on clinical response. 2
Minor Procedures
Administer weight-based dosing: 2 mg/kg IV or IM in children; adults typically receive 50-100 mg as a single dose. 2, 4
Adrenal Crisis Management
For suspected or confirmed adrenal crisis, immediately administer hydrocortisone 100 mg IV bolus, followed by 50-100 mg IV every 6-8 hours (or 200 mg/24h continuous infusion), plus aggressive fluid resuscitation with at least 1-2 liters normal saline in the first hour. 1, 5, 6
- If IV access cannot be established quickly, give hydrocortisone IM without delay—do not wait for venous access 5
- If hydrocortisone is unavailable, prednisolone or methylprednisolone may be substituted 5
- Correct hypoglycemia, hyponatremia, and hyperkalemia concurrently 5
- Taper stress-dose steroids to maintenance levels over 5-7 days once the patient is stabilized 1
- Infections are the most common precipitating cause of adrenal crisis 6
Special Populations
Pediatric Dosing
For surgical stress coverage in children, administer hydrocortisone 2 mg/kg IV/IM at induction. 2, 4
Postoperatively, continue hydrocortisone 2 mg/kg IM every 4 hours or use weight-based continuous infusion: 4, 7
- Up to 10 kg: 25 mg/24h
- 11-20 kg: 50 mg/24h
- Over 20 kg (prepubertal): 100 mg/24h
- Over 20 kg (pubertal): 150 mg/24h
Pregnancy and Labor
For vaginal delivery, give hydrocortisone 100 mg IV at onset of labor, followed by continuous infusion of 200 mg/24h. 2, 4
For Caesarean section, use the same protocol as major surgery (100 mg IV bolus followed by 200 mg/24h infusion). 2, 4
Immune Checkpoint Inhibitor-Related Adrenal Insufficiency
Grade 1 (Asymptomatic/Mild)
Continue checkpoint inhibitor with hydrocortisone replacement at maintenance doses (15-20 mg daily in divided doses). 1
Grade 2 (Moderate Symptoms)
Hold checkpoint inhibitor until stabilized; initiate stress-dose corticosteroids at 2-3 times maintenance (hydrocortisone 30-50 mg total daily or prednisone 20 mg daily), then taper to maintenance after 2 days. 1
Grade 3-4 (Severe/Life-Threatening)
Hold checkpoint inhibitor; hospitalize for IV hydrocortisone 50-100 mg every 6-8 hours plus IV fluids (at least 2L normal saline); taper to oral maintenance over 5-7 days. 1
Critical Safety Considerations
Dexamethasone Limitations
Never use dexamethasone as sole replacement therapy in primary adrenal insufficiency—it lacks mineralocorticoid activity and will not prevent adrenal crisis. 1, 4
- While 8 mg dexamethasone provides glucocorticoid coverage equivalent to 200 mg hydrocortisone for 24 hours, patients with primary adrenal insufficiency will develop life-threatening hyperkalemia and hypovolemia without mineralocorticoid replacement 1
Pharmacokinetic Considerations
Hydrocortisone has a plasma half-life of approximately 90 minutes, requiring multiple daily doses or continuous infusion during stress. 1, 8
- Half-life may be shorter in patients taking CYP3A4 inducers or with hyperthyroidism 1
- Half-life may be longer in critically ill patients 1
- Consider higher doses in obese patients and those on enzyme-inducing medications, with close monitoring for signs of adrenal crisis 1
Patient Education Essentials
All patients with adrenal insufficiency must receive education on stress dosing, carry an emergency card/medical alert bracelet, and have access to an emergency injectable hydrocortisone kit with self-injection training. 1, 2, 5, 6
- Patients should know to double or triple their oral dose during minor illness (fever, gastroenteritis) 5
- Instruct patients to seek immediate medical attention for vomiting, severe illness, or inability to take oral medications 5
- Arrange endocrinology consultation before any planned surgery or high-stress treatments 1
HPA Axis Suppression
Patients on chronic glucocorticoid therapy (including inhaled corticosteroids at standard doses) may have hypothalamic-pituitary-adrenal axis suppression requiring stress-dose coverage. 1, 2
- Approximately one-third to one-half of patients taking ≥5 mg prednisolone daily demonstrate inadequate adrenal reserve on testing 1
- When in doubt about the need for stress-dose coverage, always provide it—short-term glucocorticoid supplementation has no long-term adverse consequences, but withholding it can be fatal 1