What is the appropriate management for an adult patient with suspected adrenal insufficiency, given an Adrenocorticotropic Hormone (ACTH) stimulation test with cortisol levels of 1.8, 5.3, and 7.8, and an ACTH level less than 5, indicating secondary adrenal insufficiency?

Secondary Adrenal Insufficiency Confirmed – Initiate Lifelong Glucocorticoid Replacement

This patient has confirmed secondary adrenal insufficiency based on a failed ACTH stimulation test (peak cortisol 7.8 μg/dL, well below the diagnostic threshold of 18 μg/dL) combined with suppressed ACTH (<5 pg/mL), and requires immediate initiation of lifelong glucocorticoid replacement therapy. 1, 2

Interpretation of Test Results

Your patient's results definitively confirm secondary adrenal insufficiency:

• ACTH stimulation test cortisol values of 1.8,5.3, and 7.8 μg/dL – The peak cortisol of 7.8 μg/dL is far below the normal threshold of >18-20 μg/dL (>500-550 nmol/L), confirming adrenal insufficiency 1, 2
• ACTH level <5 pg/mL – This suppressed ACTH with low cortisol establishes the diagnosis as secondary (central) adrenal insufficiency rather than primary adrenal insufficiency, where ACTH would be elevated 1, 2
• The pattern of low cortisol with low/suppressed ACTH indicates pituitary or hypothalamic dysfunction 1, 2

Immediate Management: Initiate Glucocorticoid Replacement

Standard Maintenance Therapy

Begin hydrocortisone 15-25 mg daily in divided doses – this is the preferred glucocorticoid because it allows recreation of the diurnal cortisol rhythm 1, 3, 2:

• Typical regimen: 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM 1
• Alternative effective regimens include 15+5 mg or 10+10 mg depending on individual response 1
• Alternative agent: Prednisone 3-5 mg daily (20 mg hydrocortisone = 5 mg prednisone) 3, 2

Key Difference from Primary Adrenal Insufficiency

Do NOT add fludrocortisone – Secondary adrenal insufficiency requires only glucocorticoid replacement because the renin-angiotensin-aldosterone system remains intact (mineralocorticoid function is preserved) 1, 3, 2

Investigate the Underlying Cause

Secondary adrenal insufficiency requires evaluation for pituitary or hypothalamic pathology 2, 4:

• Obtain MRI of the pituitary/sella to evaluate for pituitary tumors, hemorrhage, empty sella, or infiltrative disease 1, 4
• Screen for other pituitary hormone deficiencies: TSH/free T4, LH/FSH, prolactin, IGF-1 1
• Review medication history for opioids, exogenous glucocorticoids, or other medications that suppress ACTH production 2, 5

Critical pitfall: If concurrent hypothyroidism is identified, always start glucocorticoid replacement several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1, 3

Essential Patient Education and Safety Measures

Stress Dosing Protocol

All patients with adrenal insufficiency must understand how to adjust their glucocorticoid dose during illness 1, 3, 2:

• Minor illness (cold, fever): Double the usual daily dose until recovery, continue for 24-48 hours after symptoms resolve 3
• Moderate illness (persistent vomiting, high fever): Triple the usual dose or use 2-3 times maintenance (hydrocortisone 30-50 mg total daily) 1, 3
• Severe illness, trauma, or inability to take oral medications: Immediate medical attention required – administer hydrocortisone 100 mg IV/IM bolus, followed by 100 mg every 6-8 hours 1, 3, 2

Emergency Preparedness

Mandatory safety measures 1, 3, 2:

• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 3
• Medical alert bracelet or necklace indicating adrenal insufficiency 1, 3, 2
• Written stress-dosing instructions for the patient and family members 3

Perioperative Management

For any surgery or procedure 3:

• Minor procedures: Double oral dose on day of procedure 3
• Major surgery: Hydrocortisone 100 mg IV at induction, followed by continuous infusion of 200 mg/24 hours, then taper as patient recovers 3
• Endocrine consultation recommended for stress-dose planning before surgery 1

Monitoring and Follow-Up

Initial Follow-Up

• Reassess in 2-4 weeks to evaluate symptom response and adjust dosing if needed 6
• Monitor for signs of under-replacement: persistent fatigue, nausea, weight loss, hypotension 1
• Monitor for signs of over-replacement: weight gain, hypertension, hyperglycemia, cushingoid features 1

Long-Term Monitoring

Annual follow-up should include 3:

• Assessment of health, well-being, and weight 3
• Blood pressure measurement (supine and standing) 1
• Serum electrolytes 3
• Screen periodically for new autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density every 3-5 years to assess for complications of glucocorticoid therapy 1

Critical Pitfalls to Avoid

• Never attempt to discontinue hydrocortisone – Secondary adrenal insufficiency from non-iatrogenic causes is permanent and stopping replacement will precipitate life-threatening adrenal crisis 1
• Never delay treatment if adrenal crisis is suspected – Mortality is high if untreated; give hydrocortisone 100 mg IV immediately plus 0.9% saline infusion at 1 L/hour 1, 3, 2
• Do not use dexamethasone for long-term replacement in primary adrenal insufficiency (though this patient has secondary AI, this remains an important distinction) 3
• Avoid medications that increase cortisol clearance without dose adjustment: anticonvulsants, rifampin, barbiturates may require higher replacement doses 1