What is the primary treatment for a patient with secondary adrenal insufficiency?

Treatment of Secondary Adrenal Insufficiency

The primary treatment for secondary adrenal insufficiency is physiologic glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, typically given as 10 mg upon waking, 5 mg at midday, and 2.5-5 mg in the late afternoon to mimic the natural cortisol rhythm. 1, 2

Glucocorticoid Replacement Regimen

Maintenance therapy consists of hydrocortisone as the preferred agent because it allows recreation of the diurnal cortisol rhythm. 1, 2 The standard dosing protocol includes:

• Total daily dose: 15-25 mg hydrocortisone in split doses 1, 2
• First dose immediately upon waking (e.g., 10 mg at 7:00 AM) 1, 2
• Second dose at midday (e.g., 5 mg at 12:00 PM) 1, 2
• Third dose in late afternoon, at least 6 hours before bedtime (e.g., 2.5-5 mg at 4:00 PM) 1, 2
• Alternative effective regimens include 15+5 mg or 10+10 mg depending on individual response 3

Use the lowest dose compatible with health and sense of well-being. 1, 2 For patients experiencing marked fluctuations in energy throughout the day, prednisolone 4-5 mg daily may be considered as an alternative. 3

Key Distinction: No Mineralocorticoid Needed

Unlike primary adrenal insufficiency, secondary adrenal insufficiency does NOT require mineralocorticoid (fludrocortisone) replacement because the renin-angiotensin-aldosterone system remains intact. 1, 3 This is a critical distinction—patients with secondary adrenal insufficiency continue to secrete aldosterone in response to renin. 1

Stress Dosing Protocol

All patients must be educated on stress dosing and provided with emergency supplies. 1, 2 The degree of supplementation depends on illness severity:

Minor Stress (fever, minor illness, dental procedures)

• Double the usual daily dose for 1-2 days 2

Moderate Stress (moderate illness, minor surgery)

• Hydrocortisone 50-75 mg daily 2
• Continue until recovered, then taper to maintenance over 2-3 days 2

Major Stress (major surgery, severe illness)

• Hydrocortisone 100 mg IV/IM at induction or onset of illness 1
• Followed by continuous infusion of 200 mg/24 hours OR 100 mg every 6-8 hours 1, 2
• Taper to oral maintenance over 1-3 days once stabilized 2

Adrenal Crisis (life-threatening)

• Hydrocortisone 100 mg IV bolus immediately—do NOT delay for diagnostic testing 1, 3, 2
• Followed by 100 mg every 6-8 hours 1
• Aggressive fluid resuscitation with 0.9% saline at 1 L/hour initially 1, 3, 2

Mandatory Patient Education and Safety Measures

Every patient with secondary adrenal insufficiency requires comprehensive education and emergency preparedness: 1, 2

• Wear medical alert identification jewelry or bracelet indicating adrenal insufficiency 1, 2
• Carry a steroid emergency card at all times 1
• Possess emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 2
• Understand warning signs of adrenal crisis: severe weakness, confusion, abdominal pain, vomiting, hypotension 2
• Know to double or triple doses during illness, fever, or physical stress 2

Monitoring and Follow-up

Patients should be reviewed at least annually with assessment of: 1

• Weight and blood pressure measurement 1, 2
• Serum electrolytes 1, 2
• Clinical symptoms of under-replacement: fatigue, nausea, weight loss, hypotension 2
• Clinical symptoms of over-replacement: weight gain, hypertension, hyperglycemia, Cushingoid features 4

Critical Pitfalls to Avoid

Never delay treatment of suspected adrenal crisis for diagnostic procedures—mortality is high if untreated. 1, 3, 2 If in doubt about the need for glucocorticoids, they should be given as there are no long-term adverse consequences of short-term administration. 1

Chronic glucocorticoid therapy (prednisolone ≥5 mg daily for ≥1 month) is the most common cause of secondary adrenal insufficiency that clinicians will encounter. 1 These patients are at significant risk of adrenal crisis during surgical stress or illness. 1

When treating concurrent hypothyroidism and adrenal insufficiency, always start corticosteroids first—initiating thyroid hormone before adequate glucocorticoid replacement can precipitate adrenal crisis. 3, 2, 5

Drug-induced secondary adrenocortical insufficiency may persist for months after discontinuation of therapy; therefore, hormone therapy should be reinstituted during any stressful situation occurring during that period. 6