What is the treatment for corticotropic (adrenocorticotropic hormone) deficiency?

Treatment of Corticotropic (ACTH) Deficiency

Lifelong glucocorticoid replacement with hydrocortisone 15-25 mg/day or cortisone acetate 25-37.5 mg/day, divided into 2-3 doses with the largest dose in the morning, is the cornerstone of treatment for corticotropic deficiency. 1, 2

Glucocorticoid Replacement Therapy

Preferred Medications and Dosing

• Hydrocortisone (HC) or cortisone acetate (CA) are the preferred glucocorticoid choices, as they most closely mimic physiological cortisol 1, 2, 3
• Standard hydrocortisone dosing ranges from 15-25 mg/day, typically given as 10 mg + 5 mg + 2.5-5 mg at 07:00,12:00, and 16:00 hours 1, 2
• Cortisone acetate dosing ranges from 25-37.5 mg/day in similar divided doses 1
• The first dose should be taken immediately upon awakening, with the last dose approximately 4-6 hours before bedtime to mimic natural circadian rhythm 1
• Cortisone acetate has a slightly delayed onset as it requires hepatic conversion to hydrocortisone by 11β-hydroxysteroid dehydrogenase type 1 1

Alternative Dosing Strategies

• For patients with morning nausea or poor appetite, waking earlier to take the first dose then returning to sleep may relieve symptoms 1
• A two-dose regimen (15 mg + 5 mg or 10 mg + 10 mg) can be used for some patients 1
• Prednisolone (3-5 mg/day) may be considered in select patients experiencing marked energy fluctuations, though dexamethasone should be avoided 1

Monitoring and Dose Adjustment

Clinical Assessment

• Monitoring relies primarily on clinical assessment, as plasma ACTH and serum cortisol measurements are not useful for dose adjustment 1, 2
• Signs of over-replacement include weight gain, insomnia, and peripheral edema 1, 2
• Signs of under-replacement include lethargy, nausea, poor appetite, weight loss, and increased pigmentation 1, 2
• Assess energy levels throughout the day, mental concentration, daytime somnolence, and ease of falling asleep 1

Laboratory Monitoring

• Annual monitoring should include serum sodium, potassium, thyroid function (TSH, FT4, TPO-Ab), plasma glucose, HbA1c, complete blood count, and vitamin B12 levels 1
• In cases of suspected malabsorption, a cortisol day curve (serum or salivary) at 0,2,4, and 6 hours post-dose can guide dosing adjustments 1

Stress Dosing and Emergency Management

Illness and Stress

• Patients must double or triple their glucocorticoid dose during intercurrent illnesses, vomiting, injuries, or other stressors 1
• All patients should be trained in intramuscular hydrocortisone administration for emergency use 1, 2
• Patients should wear a Medic Alert bracelet and carry a steroid emergency card at all times 1, 2

Acute Adrenal Crisis

• Immediate treatment with hydrocortisone 100 mg IV bolus is critical and must not be delayed for diagnostic testing 1, 4
• Follow with 100-300 mg/day as continuous infusion or IV/IM boluses every 6 hours 1
• Administer 3-4 liters of isotonic saline, with initial infusion rate of approximately 1 L/hour 1
• Continue IV saline at slower rate for 24-48 hours with frequent hemodynamic monitoring 1
• Taper parenteral glucocorticoids over 1-3 days to oral maintenance doses 1

Important Caveats and Drug Interactions

Medication Interactions

• CYP3A4 is the key enzyme affecting hydrocortisone clearance, and concomitant medications (rifampin, phenytoin, carbamazepine) can significantly reduce hydrocortisone efficacy, requiring dose adjustments 1, 2

Mineralocorticoid Considerations

• Unlike primary adrenal insufficiency, mineralocorticoid replacement is typically NOT required in isolated corticotropic deficiency, as the renin-angiotensin-aldosterone system remains intact 1
• However, if high-dose hydrocortisone (>50 mg/day) is used during stress, mineralocorticoid effects are provided by the glucocorticoid itself 1

Patient Education Priorities

• Education on self-management during illness is paramount to prevent adrenal crises, which carry significant mortality risk 1
• Many patients must advocate for themselves in emergency settings, highlighting the critical need for improved healthcare provider awareness 1
• Delays in hydrocortisone administration during emergencies can be fatal 2

Screening for Associated Conditions

• Monitor thyroid function every 12 months, as subclinical thyroid disease can contribute to persistent fatigue 1
• Screen annually for diabetes mellitus, anemia, and vitamin B12 deficiency 1