What is the recommended treatment for a patient with low Adrenocorticotrophic Hormone (ACTH) levels?

Treatment for Low ACTH (Secondary Adrenal Insufficiency)

Initiate glucocorticoid replacement therapy with hydrocortisone 15-25 mg daily, divided into 2-3 doses, with the first dose upon awakening and the last dose 4-6 hours before bedtime. 1

Glucocorticoid Replacement Strategy

First-Line Treatment

• Hydrocortisone is the preferred glucocorticoid because it best recreates the physiological diurnal rhythm of cortisol 1, 2
• Start with 15-20 mg daily in divided doses (typically 2/3 in the morning, 1/3 in early afternoon) for mild symptoms 1, 2
• Common regimens include: 10 mg + 5 mg + 2.5 mg (at 07:00,12:00,16:00) or 15 mg + 5 mg (at 07:00,12:00) 1
• Cortisone acetate (25-37.5 mg daily) is an acceptable alternative, though it has a slightly delayed onset requiring hepatic activation 1

Dosing Based on Symptom Severity

Mild symptoms (Grade 1):

• Hydrocortisone 15-20 mg daily in divided doses 1, 2
• Can continue normal activities with close monitoring 1

Moderate symptoms (Grade 2):

• Initiate 2-3 times maintenance dosing: hydrocortisone 30-50 mg total daily or prednisone 20 mg daily 1, 2
• Taper to maintenance doses over 5-10 days as symptoms improve 1, 3
• Consider endocrine consultation 1

Severe symptoms (Grade 3-4):

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

Critical Timing Considerations

• Always start corticosteroids FIRST before initiating other hormone replacements (thyroid, testosterone, estrogen) as these hormones accelerate cortisol clearance and can precipitate adrenal crisis 1, 2
• Take the first dose immediately upon awakening to mimic physiological cortisol peak 1
• For patients with morning nausea or fatigue, consider waking earlier to take the first dose, then returning to sleep 1

Monitoring and Dose Adjustment

• Clinical assessment is the primary monitoring tool - plasma ACTH and serum cortisol are not useful for dose adjustment 1
• Signs of over-replacement: weight gain, insomnia, peripheral edema, hypertension, hyperglycemia 1, 2
• Signs of under-replacement: lethargy, nausea, poor appetite, weight loss, increased pigmentation 1
• Adjust doses based on energy levels, mental concentration, daytime somnolence, and timing of energy dips throughout the day 1

Mineralocorticoid Considerations

• Low ACTH with low cortisol indicates secondary (central) adrenal insufficiency - these patients typically do NOT require fludrocortisone as the renin-angiotensin-aldosterone system remains intact 1, 2
• Only add fludrocortisone if there is concurrent primary adrenal insufficiency (high ACTH with low cortisol) 1, 2

Drug Interactions Requiring Dose Adjustments

Medications that may require MORE hydrocortisone: 1

• Anti-epileptics/barbiturates
• Antituberculosis medications
• Etomidate
• Topiramate

Medications that may require LESS hydrocortisone: 1

• Grapefruit juice
• Liquorice

Essential Patient Education

All patients must receive education on: 1, 2

• Stress dosing: Double or triple doses during illness, injury, or significant stress
• Emergency injectable hydrocortisone administration technique
• When to seek immediate medical attention for impending adrenal crisis
• Medical alert bracelet indicating adrenal insufficiency to trigger stress-dose corticosteroids by emergency personnel

Special Situations

• Night shift workers: Adjust timing to 10 mg upon awakening before work rather than fixed clock times 1
• Patients with marked energy fluctuations: Consider prednisolone 4-5 mg once daily or 3 mg + 1-2 mg in divided doses, though this is second-line 1
• Avoid dexamethasone as replacement therapy 1

Common Pitfall to Avoid

• Do not attempt laboratory confirmation of adrenal insufficiency in patients already receiving high-dose corticosteroids for other conditions - wait until treatment is ready to be discontinued 1
• Hydrocortisone must be held for 24 hours before assessing endogenous cortisol function 1
• In patients with recent corticosteroid use for other conditions, test HPA axis recovery after 3 months of maintenance hydrocortisone therapy 1