Hydrocortisone Dosing for Hypocortisolism (Cortisol 4.8)

Direct Recommendation

For a patient with confirmed adrenal insufficiency and a cortisol level of 4.8 (assuming μg/dL or ~132 nmol/L), prescribe hydrocortisone 15-25 mg daily in divided doses: typically 10 mg upon awakening (before 9 AM), 5 mg at noon, and 2.5-5 mg at 4 PM. 1, 2, 3

Dosing Algorithm Based on Clinical Severity

Stable Outpatient with Confirmed Diagnosis

Standard maintenance dosing: Hydrocortisone 15-25 mg daily in divided doses 1, 3
Most common effective regimens: 1
- 10 mg at 7:00 AM + 5 mg at 12:00 PM + 2.5-5 mg at 4:00 PM
- Alternative: 15 mg + 5 mg (two doses)
- Alternative: 10 mg + 10 mg (two doses)
- Alternative: 10 mg + 5 mg + 5 mg (three doses)

Moderately Symptomatic Patient

Stress-dose adjustment: 2-3 times maintenance dose = 30-50 mg hydrocortisone daily 1
Continue until symptoms stabilize, then taper to maintenance over 48 hours 1

Critically Ill or Suspected Adrenal Crisis

Immediate treatment: Hydrocortisone 100 mg IV bolus, followed by 200 mg/24h continuous infusion (or 50 mg IV/IM every 6 hours) 4, 1
Concurrent fluid resuscitation: 0.9% saline at 1 L/hour 1
Never delay treatment for diagnostic testing 1

Critical Considerations for Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency (Addison's Disease)

Requires both glucocorticoid AND mineralocorticoid replacement 1, 3
Add fludrocortisone: 0.05-0.2 mg (50-200 μg) daily 1, 5, 3
Monitor for: Salt cravings, orthostatic hypotension, hyponatremia, hyperkalemia 1, 5
Dietary recommendation: Unrestricted sodium salt intake 1, 5

Secondary Adrenal Insufficiency

Glucocorticoid replacement only (renin-angiotensin-aldosterone system remains intact) 1
No fludrocortisone needed 1

Timing and Administration Principles

The timing of hydrocortisone doses is critical to approximate physiological cortisol secretion: 1, 6

Largest dose upon awakening (before 9 AM) to mimic morning cortisol peak 6
Second dose at midday (around noon) 1
Third dose in early afternoon (around 4 PM, NOT later than 4-6 hours before bedtime to avoid insomnia) 6
No evening or nighttime doses (physiological cortisol-free interval at night) 7

Monitoring and Dose Adjustment

Clinical Assessment (Primary Method)

Signs of under-replacement: Lethargy, nausea, poor appetite, weight loss, morning symptoms, salt cravings, orthostatic hypotension 1, 6
Signs of over-replacement: Weight gain, insomnia, peripheral edema, hypertension 6
Adjust based on symptoms, NOT laboratory cortisol levels (exogenous hydrocortisone interferes with cortisol assays) 1, 6

Follow-Up Schedule

Annual review minimum: Assess health, well-being, weight, blood pressure, serum electrolytes 1, 5
Screen for autoimmune conditions: Thyroid function, diabetes, vitamin B12, celiac disease 1

Drug Interactions Requiring Dose Adjustment

Medications That INCREASE Hydrocortisone Requirements

CYP3A4 inducers: Anticonvulsants (phenytoin, carbamazepine), rifampin, barbiturates 1, 6
Other: Antituberculosis drugs, antifungals, etomidate, topiramate 1

Medications That DECREASE Hydrocortisone Requirements

CYP3A4 inhibitors: Grapefruit juice, liquorice 1, 6
Avoid these substances 1, 5

Medications That Interfere with Fludrocortisone (Primary AI Only)

Avoid or adjust: Diuretics, acetazolamide, NSAIDs, drospirenone-containing contraceptives 1, 5

Mandatory Patient Education and Safety Measures

All patients with adrenal insufficiency require the following: 1

Stress-dose education: Double or triple usual dose during illness, fever, or physical stress 1
Emergency injectable kit: Hydrocortisone 100 mg IM with self-injection training 1
Medical alert identification: Bracelet or necklace indicating adrenal insufficiency 1
Warning signs of adrenal crisis: Severe weakness, vomiting, diarrhea, confusion, hypotension 1
Endocrine consultation: For newly diagnosed patients, pre-operative planning, or recurrent crises 1

Common Pitfalls to Avoid

Never stop hydrocortisone abruptly in confirmed adrenal insufficiency (will precipitate life-threatening crisis) 1, 2
Never delay treatment for diagnostic testing if adrenal crisis is suspected 4, 1
Do not rely on electrolyte abnormalities alone (hyperkalemia present in only ~50% of primary AI cases) 1
Do not check morning cortisol levels in patients already on hydrocortisone replacement (exogenous steroid interferes with assay) 1
Do not use dexamethasone for chronic replacement (lacks mineralocorticoid activity, inadequate for primary AI) 1
Do not give evening doses (causes insomnia and does not mimic physiology) 6, 7

Special Situations

Peri-Operative Stress Dosing

Major surgery: Hydrocortisone 100 mg IV at induction, then 200 mg/24h infusion, resume oral at double dose for 48 hours 4
Minor procedures: Double usual daily dose for 1-2 days 1

Concurrent Hypothyroidism

Start corticosteroids several days BEFORE thyroid hormone replacement to prevent precipitating adrenal crisis 1

Pregnancy (Primary AI)

Fludrocortisone adjustments may be needed in the last trimester due to progesterone's anti-mineralocorticoid effects 5

What dose of hydrocortisone (cortisol replacement therapy) should be prescribed for an adult patient with hypocortisolism (cortisol level 4.8) due to primary or secondary adrenal insufficiency?

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