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

Treatment of Hypocortisolism (Low Cortisol)

Start hydrocortisone 15-20 mg daily in divided doses (10 mg morning, 5 mg early afternoon) for all patients with confirmed adrenal insufficiency, and add fludrocortisone 0.05-0.1 mg daily if primary adrenal insufficiency is present. 1, 2

Diagnostic Framework Before Treatment

• Measure morning ACTH and cortisol simultaneously to distinguish primary (high ACTH, low cortisol) from secondary (low ACTH, low cortisol) adrenal insufficiency 1, 2
• Check basic metabolic panel for hyponatremia and hyperkalemia, which suggest primary adrenal insufficiency 2
• Consider ACTH stimulation testing if morning cortisol is between 3-15 mg/dL to confirm the diagnosis 1
• Obtain MRI brain with pituitary cuts if multiple endocrine deficiencies are present or if severe headaches/visual changes occur, as this suggests secondary causes 1, 2

Treatment Algorithm by Severity

Mild Symptoms (Grade 1)

• Initiate hydrocortisone 15-20 mg daily in divided doses: give 2/3 of dose (10-13 mg) in morning and 1/3 (5-7 mg) in early afternoon to mimic diurnal cortisol rhythm 1, 2, 3
• Add fludrocortisone 0.05-0.1 mg daily for primary adrenal insufficiency (high ACTH), titrating based on blood pressure, sodium levels, and plasma renin activity (target upper half of reference range) 1, 2
• Titrate hydrocortisone up to maximum 30 mg daily if residual fatigue, weakness, or orthostatic symptoms persist 1
• Reduce dose if signs of overreplacement develop: bruising, thin skin, edema, weight gain, hypertension, or hyperglycemia 1, 2

Moderate Symptoms (Grade 2)

• Start with hydrocortisone 30-50 mg total daily dose or prednisone 20 mg daily to manage acute symptoms 1, 2
• Initiate fludrocortisone 0.05-0.1 mg daily simultaneously if primary adrenal insufficiency 1
• Taper stress-dose corticosteroids down to maintenance doses after 2 days once symptoms stabilize 1
• Provide IV hydration if volume depletion is present 1

Severe/Life-Threatening Symptoms (Grade 3-4)

• Hospitalize immediately and administer IV hydrocortisone 50-100 mg every 6-8 hours 1, 2
• Give at least 2 liters normal saline for volume resuscitation 1
• Taper IV stress-dose steroids to oral maintenance over 5-7 days 1
• Transition to maintenance therapy as outlined for Grade 1 once stabilized 1

Critical Medication Principles

• Hydrocortisone is strongly preferred over prednisone because it recreates physiological diurnal cortisol rhythm and has shorter half-life, reducing overreplacement risk 1, 2, 3
• Equivalency: hydrocortisone 20 mg = prednisone 5 mg 1, 2
• When treating multiple hormone deficiencies, always start glucocorticoids first before thyroid hormone or sex hormone replacement to prevent precipitating adrenal crisis 1, 2
• Salt supplementation or mineralocorticoid (fludrocortisone) should be administered concurrently with hydrocortisone in primary adrenal insufficiency 3

Mandatory Patient Education

• Teach stress-dosing protocol: double or triple hydrocortisone dose during illness, fever, or significant physical stress 1, 2, 3
• Provide emergency injectable hydrocortisone (100 mg IM) with instructions for use if unable to take oral medications due to vomiting 1, 2
• Obtain medical alert bracelet or necklace stating "adrenal insufficiency" to ensure emergency personnel provide stress-dose steroids 1, 2
• Educate on signs of impending adrenal crisis: severe weakness, confusion, abdominal pain, vomiting—requiring immediate emergency care 1

Monitoring and Follow-up

• Monitor blood pressure and electrolytes regularly to assess adequacy of replacement 4, 3
• Adjust fludrocortisone based on volume status, serum sodium, and plasma renin activity (target upper half of normal range) 1, 2
• Refer to endocrinology for all patients for stress-dose planning before surgery or high-stress procedures 1, 2
• Reassess need for continued replacement at 3 months if adrenal insufficiency developed after recent high-dose corticosteroid use for other conditions 1

Special Considerations

• DHEA replacement (25-50 mg daily) may be considered in women with persistent low libido or energy despite adequate cortisol replacement, though evidence is limited 1, 2
• In patients requiring both glucocorticoid and thyroid hormone replacement, establish stable cortisol replacement first, as thyroid hormone accelerates cortisol clearance and can precipitate crisis 1, 2
• Testosterone or estrogen replacement may be needed in secondary adrenal insufficiency with multiple pituitary hormone deficiencies, but only after cortisol replacement is established 1, 2

Common Pitfalls to Avoid

• Never use morning cortisol or ACTH stimulation testing to assess recovery in patients currently taking hydrocortisone—hold hydrocortisone for 24 hours before testing 1
• Do not rely on cortisol levels to diagnose overreplacement in patients on hydrocortisone; use only clinical features (weight gain, hypertension, hyperglycemia, bruising) 1, 2
• Avoid long-acting steroids like prednisone or dexamethasone for routine replacement as they increase overreplacement risk and cannot mimic diurnal rhythm 1, 2