What is the treatment for hypocortisolism (low cortisol levels)?

Treatment for Low Cortisol (Hypocortisolism)

Initiate glucocorticoid replacement therapy with hydrocortisone 15-20 mg daily in divided doses (two-thirds in the morning, one-third in the afternoon) for mild symptoms, escalating to 30-50 mg daily or prednisone 20 mg daily for moderate symptoms, and immediate IV hydrocortisone with fluid resuscitation for severe symptoms or adrenal crisis. 1

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis and distinguish between primary and secondary adrenal insufficiency:

• Measure morning ACTH and cortisol levels simultaneously: Low cortisol with high ACTH indicates primary adrenal insufficiency, while low cortisol with low ACTH suggests secondary adrenal insufficiency 1, 2
• Check basic metabolic panel: Look for hyponatremia (present in 90% of newly diagnosed cases) and hyperkalemia (present in only 50% of primary cases), though absence of these does not rule out adrenal insufficiency 2
• Perform ACTH stimulation test if initial results are indeterminate: Administer 0.25 mg cosyntropin with cortisol measurements at baseline and 30 minutes; peak cortisol <500 nmol/L (<18 µg/dL) confirms adrenal insufficiency 2

Critical pitfall: Never delay treatment in clinically unstable patients to perform diagnostic testing—draw blood samples for cortisol and ACTH, then immediately start treatment 2

Treatment Algorithm Based on Severity

Mild Symptoms (Fatigue, Weakness, Mild Hypotension)

• Start hydrocortisone 15-20 mg daily in divided doses: Give two-thirds (10-13 mg) in the morning and one-third (5-7 mg) in the afternoon to mimic physiologic diurnal rhythm 1
• Add fludrocortisone 0.05-0.1 mg daily for primary adrenal insufficiency: This replaces mineralocorticoid function, which is deficient only in primary disease 1
• Monitor for signs of over-replacement: Watch for bruising, thin skin, edema, weight gain, hypertension, and hyperglycemia, which indicate iatrogenic Cushing's syndrome and require dose reduction 1

Moderate Symptoms (Significant Fatigue, Orthostatic Hypotension, Nausea)

• Initiate higher dosing: Use hydrocortisone 30-50 mg total daily dose or prednisone 20 mg daily 1
• Taper to maintenance dose over 5-10 days: Reduce to standard maintenance dosing (hydrocortisone 15-20 mg daily) as symptoms improve 3
• Provide IV normal saline if volume depleted: Address concurrent hypotension with fluid resuscitation 3

Severe Symptoms or Adrenal Crisis (Shock, Altered Mental Status, Severe Hypotension)

• Immediate hospitalization with IV stress-dose steroids: Administer hydrocortisone 100 mg IV bolus, followed by 10 mg/hour continuous infusion (240 mg/day) or 50 mg IV every 6 hours 4
• Aggressive IV fluid resuscitation: Use 0.9% normal saline to correct volume depletion and hypotension 3, 4
• Continue for ≥7 days, then taper gradually: Do not stop abruptly, as this can precipitate recurrent crisis 4

Medication Selection and Dosing

Hydrocortisone is preferred over long-acting steroids like prednisone because it better recreates the physiologic diurnal rhythm of cortisol 1

• Hydrocortisone 20 mg is equivalent to prednisone 5 mg for dose conversions 1
• Dexamethasone is not recommended for treating adrenal insufficiency in critical illness 4

Special Consideration for Concurrent Hypothyroidism

Always start glucocorticoids first, several days before thyroid hormone replacement, to prevent precipitating adrenal crisis 1, 3. Thyroid hormone increases cortisol metabolism and can unmask or worsen adrenal insufficiency 1.

Essential Patient Education and Safety Measures

Every patient with adrenal insufficiency requires comprehensive education on stress dosing and emergency preparedness:

• Stress dosing protocol: Double or triple maintenance doses during illness, fever, or significant stress 1
• Provide emergency injectable hydrocortisone: Give patients a home supply with clear instructions for use during vomiting or inability to take oral medications 1
• Medical alert bracelet: All patients must wear identification indicating adrenal insufficiency 1
• Endocrine consultation before surgery: Plan stress-dose steroids for any surgical procedures 2

Monitoring and Follow-up

• Schedule follow-up in 2-4 weeks: Reassess symptoms and adjust medication dosing based on clinical response 3
• Monitor blood pressure and electrolytes regularly: Check for adequate replacement without over-treatment 5
• Gradual dose reduction when tapering: Avoid abrupt discontinuation, which can cause drug-induced secondary adrenal insufficiency that may persist for months 6

Additional Hormone Replacement Considerations

In patients with multiple pituitary hormone deficiencies:

• Establish cortisol replacement first: Wait until glucocorticoid therapy is stable before adding other hormones 1
• Consider DHEA replacement in women: May benefit those with low libido or energy despite adequate cortisol replacement 1
• Add testosterone or estrogen as needed: Only after cortisol replacement is optimized 1

Critical Pitfalls to Avoid

• Do not rely solely on electrolyte abnormalities: Hyponatremia may be only marginally reduced, and hyperkalemia is absent in 50% of cases 2
• Do not use exogenous steroids before diagnostic testing: Prednisolone, dexamethasone, and even inhaled fluticasone can confound cortisol measurements 2
• Do not stop steroids abruptly: Taper gradually to prevent withdrawal and recurrent insufficiency 6, 4
• Do not forget mineralocorticoid replacement in primary disease: Salt and/or fludrocortisone must be administered concurrently with hydrocortisone 6