What is the treatment for low adrenocorticotropic hormone (ACTH) levels?

Treatment for Low Adrenocorticotropic Hormone (ACTH) Levels

The treatment for low ACTH levels (secondary adrenal insufficiency) requires hormone replacement with hydrocortisone 15-20 mg daily in divided doses (typically 2/3 in the morning and 1/3 in the early afternoon) as the primary therapy. 1, 2

Diagnostic Confirmation

• Low ACTH with low cortisol is diagnostic of secondary adrenal insufficiency, distinguishing it from primary adrenal insufficiency (which presents with high ACTH and low cortisol) 1, 2
• Evaluate morning ACTH and cortisol levels, along with basic metabolic panel to check for electrolyte abnormalities 1, 3
• Consider MRI of the brain with pituitary/sellar cuts in patients with multiple endocrine abnormalities or new severe headaches 1, 2

Treatment Algorithm Based on Symptom Severity

Mild Symptoms

• Initiate hormone replacement with hydrocortisone 15-20 mg daily in divided doses (typically 10-15 mg in the morning and 5-10 mg in early afternoon) 1, 4
• Consider endocrine consultation for optimization of therapy 1, 2
• If multiple hormone deficiencies are present, always start corticosteroids first before other hormone replacements to prevent precipitating adrenal crisis 1, 2

Moderate Symptoms

• Consider higher initial dosing: hydrocortisone 30-50 mg total daily dose or prednisone 20 mg daily 2, 1
• Taper stress-dose corticosteroids down to maintenance doses after 2-5 days 2, 1
• Clinic evaluation to assess need for hydration and supportive care 2

Severe Symptoms or Adrenal Crisis

• Immediate hospitalization with IV normal saline (at least 2L) and IV stress-dose corticosteroids (hydrocortisone 50-100 mg every 6-8 hours) 2
• Taper stress-dose corticosteroids down to oral maintenance doses over 5-7 days 2, 1
• Transition to maintenance therapy as in mild symptoms 2

Long-term Management

• Maintenance therapy with hydrocortisone 15-25 mg daily in divided doses (first dose immediately after waking, last dose not less than 6 hours before bedtime) 2, 1
• In children, hydrocortisone dosing should be 6-10 mg/m² of body surface area 2
• Use the lowest dose compatible with health and a sense of well-being 2
• Educate patients on stress dosing (doubling or tripling doses during illness, surgery, or significant stress) 2, 1
• Provide medical alert bracelet/card for adrenal insufficiency to trigger stress-dose corticosteroids by emergency services 2, 1
• Endocrine consultation prior to surgery or any procedure for stress-dose planning 2, 1

Special Considerations

• Using hydrocortisone allows for recreation of the diurnal rhythm of cortisol 2, 5
• Long-acting steroids such as prednisone can be used in special circumstances (e.g., if a patient cannot adhere to a short-acting steroid regimen), but carry risk of over-replacement 2, 6
• Hydrocortisone 20 mg is equivalent to prednisone 5 mg 2
• Unlike primary adrenal insufficiency, mineralocorticoid replacement (fludrocortisone) is generally not necessary in secondary adrenal insufficiency as aldosterone production is maintained 4, 2
• If prednisone is used instead of hydrocortisone, it is recommended that it be withdrawn gradually rather than abruptly after long-term therapy 6

Patient Education

• All patients need education on stress dosing for sick days, use of emergency injectable steroids, and when to seek medical attention for impending adrenal crisis 2
• Supplies to allow self-injection of parenteral hydrocortisone should be provided 2
• Treatment should never be delayed by diagnostic procedures if adrenal crisis is suspected 2, 3