What is the initial treatment for a patient with confirmed low cortisol (hypocortisolism)?

Initial Treatment for Confirmed Low Cortisol (Hypocortisolism)

Immediately initiate hydrocortisone 15-20 mg daily in divided doses (typically 10 mg upon awakening and 5 mg in early afternoon) for all patients with confirmed low cortisol, regardless of whether the cause is primary or secondary adrenal insufficiency. 1, 2

Diagnostic Workup Before Treatment

Before initiating therapy, obtain the following to guide management:

• Morning ACTH level to distinguish primary (ACTH >2-3x upper limit of normal) from secondary adrenal insufficiency (low ACTH with low cortisol) 1, 2
• Basic metabolic panel to check for hyponatremia, hyperkalemia, and hypoglycemia 1
• Renin and aldosterone levels if primary adrenal insufficiency is suspected 1
• ACTH stimulation test only if morning cortisol is indeterminate (3-15 mg/dL), as values <3 mg/dL confirm adrenal insufficiency 1

Initial Glucocorticoid Replacement

Mild Symptoms (Grade 1)

• Start hydrocortisone 15-20 mg daily in 2-3 divided doses: two-thirds (10 mg) upon awakening and one-third (5 mg) in early afternoon, at least 4-6 hours before bedtime 1, 2
• Titrate up to maximum 30 mg daily if residual symptoms of adrenal insufficiency persist (lethargy, nausea, poor appetite) 1
• Reduce dose if signs of iatrogenic Cushing's syndrome develop (weight gain, insomnia, peripheral edema, bruising, hypertension) 1

Moderate Symptoms (Grade 2)

• Initiate hydrocortisone 30-50 mg daily total dose (or prednisone 20 mg daily equivalent) for 2 days to manage acute symptoms 1, 2
• Taper to maintenance doses (15-20 mg hydrocortisone daily) after initial 2-day stress dosing 1
• Assess need for IV hydration and supportive care in clinic setting 1

Severe Symptoms (Grade 3-4)

• Hospitalize immediately for adrenal crisis management 1, 2
• IV stress-dose hydrocortisone 50-100 mg every 6-8 hours as initial dosing 1
• IV normal saline at least 2 liters for volume resuscitation 1
• Taper stress-dose steroids to oral maintenance over 5-7 days once stabilized 1

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Most patients with primary adrenal insufficiency require fludrocortisone 0.05-0.1 mg daily, started after glucocorticoid replacement is initiated 1, 2

• Adjust fludrocortisone dose based on volume status, sodium level, and renin response (target upper half of reference range) 1
• Secondary adrenal insufficiency does NOT require mineralocorticoid replacement as the renin-angiotensin-aldosterone system remains intact 1

Critical Timing Considerations

When Multiple Hormone Deficiencies Exist

Always start corticosteroids FIRST before initiating thyroid hormone or other hormone replacement, as other hormones accelerate cortisol clearance and can precipitate adrenal crisis 1, 2

Medication Choice

• Hydrocortisone is strongly preferred over prednisone because it recreates the diurnal cortisol rhythm when given in divided doses 1, 2
• Prednisone (4-5 mg daily) should only be used in select patients with marked energy fluctuations or compliance problems with short-acting regimens 1, 3
• Equivalence: 20 mg hydrocortisone = 5 mg prednisone 1, 3, 4

Monitoring and Dose Adjustment

Clinical assessment is the primary method for monitoring adequacy, not laboratory values 1, 2

Signs of Under-Replacement

• Lethargy, nausea, poor appetite, weight loss, increased pigmentation 1, 3
• Morning symptoms suggest need for earlier or higher morning dose 1

Signs of Over-Replacement

• Weight gain, insomnia, peripheral edema, bruising, thin skin, hypertension, hyperglycemia 1, 3

Essential Patient Education (Day 1)

All patients must receive immediate education on:

• Stress dosing: Double or triple doses during illness, injury, or surgery 1, 2
• Emergency injectable hydrocortisone with instructions for use 1, 2
• Medical alert bracelet or necklace for adrenal insufficiency 1, 2
• When to seek emergency care: persistent vomiting, severe illness, inability to take oral medications 1, 2

Common Pitfalls to Avoid

• Never delay glucocorticoid replacement to wait for ACTH stimulation test results if clinical suspicion is high and morning cortisol is <3 mg/dL 1
• Never start thyroid hormone before glucocorticoids in patients with multiple pituitary hormone deficiencies 1, 2
• Never use dexamethasone for chronic replacement as it provides no mineralocorticoid activity and has excessive glucocorticoid potency 1
• Never give the last hydrocortisone dose after 4-6 hours before bedtime as this causes insomnia 1, 3

Drug Interactions Requiring Dose Adjustment

Increase hydrocortisone dose when patients are taking:

• Anticonvulsants/barbiturates (induce cortisol metabolism) 1, 3
• Antituberculosis medications (rifampin) 1, 3

Consider dose reduction with:

• Antifungal drugs (inhibit cortisol metabolism) 1

Endocrinology Referral

Refer to endocrinology for all patients with confirmed adrenal insufficiency for ongoing management, education on stress dosing, and long-term monitoring 1, 2