How are low cortisol symptoms managed?

Management of Low Cortisol Symptoms

Initiate hydrocortisone replacement therapy with a thrice-daily regimen of 10 mg upon waking, 5 mg at lunch, and 5 mg in the evening (total 20 mg/day or 10-12 mg/m²/day), as this dosing schedule achieves optimal replacement in 60-66% of patients compared to only 15% with twice-daily regimens. 1, 2

Severity-Based Treatment Algorithm

Mild Symptoms (Fatigue, Nausea, Poor Appetite)

• Start hydrocortisone 15-20 mg daily in divided doses: 10 mg upon waking, 5 mg at lunch, 5 mg in evening 3
• For primary adrenal insufficiency (high ACTH with low cortisol), add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 3
• Monitor for symptom improvement over 2-4 weeks and adjust dosing based on clinical response 4

Moderate Symptoms (Significant Lethargy, Weight Loss, Orthostatic Symptoms)

• Initiate outpatient treatment at 2-3 times maintenance dose: hydrocortisone 30-50 mg total daily or prednisone 20 mg daily 4, 3
• Taper to maintenance dose (20 mg hydrocortisone daily) over 5-10 days as symptoms improve 4
• For primary adrenal insufficiency, add fludrocortisone 0.05-0.1 mg daily 3

Severe Symptoms or Adrenal Crisis (Hypotension, Vomiting, Collapse)

• Administer hydrocortisone 100 mg IV bolus immediately—never delay treatment for diagnostic testing 1, 3
• Follow with either continuous infusion of 200 mg over 24 hours or 50 mg IV/IM every 6 hours 3
• Provide IV normal saline at 1 L/hour for volume resuscitation 1, 4
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy 1

Rationale for Thrice-Daily Dosing

Thrice-daily hydrocortisone regimens result in significantly less prolonged hypocortisolemia compared to twice-daily dosing, with patients experiencing only 2.1 waking hours below reference range versus 5.5 hours with twice-daily dosing 5. The traditional twice-daily regimen creates:

• Supraphysiological peaks 2 hours after morning dose (median 629 nmol/L) 6
• Prolonged unphysiological nadir from 1400-1800h (median 42 nmol/L at 1600h) 6
• Negligible cortisol during early morning hours (median 15 nmol/L at 0600h) 6
• 64% of patients experience prolonged hypocortisolemia (cortisol <50 nmol/L for ≥4 hours) with twice-daily dosing versus 0% with thrice-daily dosing 5

Critical Dosing Principles

Dose Timing and Distribution

• Give highest dose (10 mg) immediately upon waking to replicate the physiological cortisol rise 3, 2
• Administer second dose (5 mg) at lunch (approximately 1230h) to prevent afternoon nadir 2
• Give third dose (5 mg) in early evening (approximately 1730h) before dinner 2
• Morning doses >4 mg/m² cause larger postdose peaks (151 nmol/L above 97.5th percentile) but do not prolong time to nadir 5

Adjusting for Individual Needs

• Total daily dose typically ranges 15-25 mg hydrocortisone (or 10-12 mg/m²/day in children) 1, 3
• Hydrocortisone 20 mg is equivalent to prednisone 5 mg 3
• For morning nausea and poor appetite, consider taking first dose earlier and returning to sleep 1
• Reduce maintenance dosing if signs of iatrogenic Cushing's develop (bruising, thin skin, edema, weight gain, hypertension, hyperglycemia) 3

Essential Patient Education

Stress Dosing Protocol

• Double or triple the regular dose during illness, fever, or significant stress 3
• For surgery under general anesthesia: hydrocortisone 100 mg IV at induction, followed by 200 mg/24h continuous infusion or 50 mg IV/IM every 6 hours 3
• After uncomplicated surgery, double oral replacement dose for 48 hours; extend up to one week for major surgery 3

Safety Measures

• Provide emergency injectable hydrocortisone with instructions for use 3
• All patients must wear medical alert bracelet indicating adrenal insufficiency 1, 3
• Educate on carrying adequate medication supply for emergencies 1
• Warn patients on immunosuppressant doses to avoid exposure to chicken pox or measles 7

Special Considerations and Pitfalls

When Starting Multiple Hormone Replacements

• Always start glucocorticoids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1, 3
• In patients with multiple hormone deficiencies, establish cortisol replacement before adding testosterone or estrogen 3

Monitoring and Follow-up

• Schedule follow-up in 2-4 weeks to reassess symptoms and adjust medication 4
• Monitor blood pressure and serum electrolytes regularly, especially in primary adrenal insufficiency 1
• Annual screening for associated autoimmune conditions (thyroid, diabetes, pernicious anemia, celiac disease) 1

Drug Interactions to Avoid

• Exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) can suppress HPA axis and confound testing 1
• Potassium-depleting diuretics enhance hypokalemia—check serum potassium frequently and supplement if necessary 8
• Digitalis glycosides increase risk of arrhythmias with hypokalemia—monitor potassium levels 8
• Oral anticoagulants have decreased prothrombin time response—monitor and adjust dosing 8

Common Pitfalls

• Do not rely solely on electrolyte abnormalities for diagnosis—hyperkalemia is present in only 50% of primary adrenal insufficiency cases 1
• Avoid using long-acting steroids like prednisone as first-line therapy, as hydrocortisone better recreates diurnal cortisol rhythm 3, 9
• Drug-induced secondary adrenocortical insufficiency may persist for months after discontinuation of therapy—reinstitute hormone therapy during any stressful situation 7
• Never fast a child with adrenal insufficiency for more than 6 hours 3