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

Treatment for Hypocortisolism (Low Cortisol Levels)

The treatment for hypocortisolism requires hormone replacement therapy with hydrocortisone at doses of 15-20 mg daily in divided doses, with 2/3 in the morning and 1/3 in the early afternoon, along with fludrocortisone (0.05-0.1 mg daily) for primary adrenal insufficiency. 1

Diagnostic Considerations

• Low cortisol with low ACTH indicates secondary adrenal insufficiency, while low cortisol with high ACTH indicates primary adrenal insufficiency 2
• Morning ACTH and cortisol levels, along with basic metabolic panel to check for electrolyte abnormalities, are essential for diagnosis 2
• Consider MRI of the brain with pituitary/sellar cuts in patients with multiple endocrine abnormalities or new severe headaches to identify potential causes of secondary adrenal insufficiency 2

Treatment Algorithm Based on Severity

Mild Symptoms

• Initiate replacement therapy with hydrocortisone 15-20 mg in divided doses (2/3 morning, 1/3 afternoon) 1
• Titrate hydrocortisone to maximum of 30 mg daily total dose for residual symptoms 1
• For primary adrenal insufficiency, add fludrocortisone (0.05-0.1 mg/day) to replace mineralocorticoid function 1
• Reduce maintenance dosing if signs of iatrogenic Cushing's syndrome develop (bruising, thin skin, edema, weight gain, hypertension, hyperglycemia) 1

Moderate Symptoms

• Consider higher initial dosing: hydrocortisone 30-50 mg total dose or prednisone 20 mg daily 1
• Initiate fludrocortisone (0.05-0.1 mg/day) for primary adrenal insufficiency 1
• Taper stress-dose corticosteroids down to maintenance doses after 2 days 1
• Assess need for hydration and supportive care 1

Severe Symptoms/Adrenal Crisis

• Immediate hospitalization is required 1
• Administer IV normal saline (at least 2L) for volume resuscitation 1
• IV stress-dose steroids: Hydrocortisone 50-100 mg every 6-8 hours initially 1
• Taper stress-dose corticosteroids down to oral maintenance doses over 5-7 days 1

Medication Considerations

• Hydrocortisone is preferred over long-acting steroids like prednisone as it better recreates the diurnal rhythm of cortisol 1
• Hydrocortisone 20 mg is equivalent to prednisone 5 mg 1
• Conventional twice-daily hydrocortisone cannot perfectly provide the physiological rhythm of cortisol release, often resulting in temporary over- or under-replacement 3
• When both glucocorticoid and thyroid replacement are needed, always start glucocorticoids first to prevent precipitating adrenal crisis 2

Patient Education and Follow-up

• All patients need education on stress dosing for sick days (doubling or tripling doses) 1, 2
• Provide emergency injectable hydrocortisone and instructions for use 1
• Recommend medical alert bracelet for adrenal insufficiency 1, 2
• Endocrine consultation should be part of planning before surgery or high-stress treatments 1
• Monitor for signs of over-replacement (weight gain, hypertension, hyperglycemia) or under-replacement (fatigue, nausea, hypotension) 4

Special Considerations

• In patients with multiple hormone deficiencies, testosterone or estrogen replacement may be needed after cortisol replacement is established 5, 2
• DHEA replacement may be considered in women with low libido and/or energy who are otherwise well-replaced with cortisol 1, 5
• Patients on immunosuppressant doses of corticosteroids should avoid exposure to chickenpox or measles 4, 6
• Drug interactions may occur with amphotericin B, potassium-depleting diuretics, digitalis glycosides, oral anticoagulants, antidiabetic drugs, and aspirin 6

Common Pitfalls and Caveats

• Abrupt withdrawal of corticosteroid therapy can lead to adrenal crisis; always taper gradually 4
• Conventional twice-daily hydrocortisone regimens result in supraphysiological peaks and unphysiological nadirs, which may affect quality of life 7
• Morning cortisol levels are often negligible during conventional replacement, potentially leading to early morning hypoglycemia 7
• Patients with adrenal insufficiency, even when on treatment, may have reduced quality of life and increased mortality compared to the general population 3