What is the best way to determine if a patient still requires steroid therapy for presumed central adrenal insufficiency?

Assessing Ongoing Need for Steroid Therapy in Presumed Central Adrenal Insufficiency

Laboratory confirmation of adrenal insufficiency cannot be performed while a patient is actively taking corticosteroids for other conditions; testing must be deferred until the patient is ready to discontinue corticosteroid treatment, at which point endocrinology consultation for a recovery and weaning protocol using hydrocortisone is essential. 1

Key Principle: Timing of Assessment

You cannot accurately test for central adrenal insufficiency while the patient is on exogenous corticosteroids. 1 The work-up cannot be done with a simple morning cortisol in a patient on corticosteroids for other conditions because the exogenous steroids suppress the hypothalamic-pituitary-adrenal (HPA) axis and interfere with interpretation of results. 1

When to Consider Testing

Prerequisites for Testing

• The patient must be clinically ready to discontinue corticosteroid therapy 1
• For patients on long-term glucocorticoid exposure, endocrinology consultation is required for establishing a recovery and weaning protocol 1
• Testing should be deferred until treatment with corticosteroids is ready to be discontinued 1

Structured Approach to Assessment

Step 1: Taper to Physiologic Doses

• Gradually taper the patient to physiologic replacement doses of hydrocortisone (typically 15-25 mg daily in divided doses: 10-20 mg morning, 5-10 mg early afternoon) 1, 2
• This mimics natural cortisol rhythm and allows assessment of the HPA axis 2

Step 2: Initial Cortisol Testing

• Measure morning cortisol 4 weeks after tapering to physiologic doses 3
• This timing allows the HPA axis time to potentially recover while maintaining patient safety 3

Step 3: Definitive Testing with ACTH Stimulation

• After discontinuing glucocorticoids, perform a low-dose ACTH stimulation test (cosyntropin challenge) 1, 4, 5
• The ACTH stimulation test is the gold standard for confirming or excluding central adrenal insufficiency 4, 6
• A cortisol peak >500 nmol/L (approximately 18 mcg/dL) excludes central adrenal insufficiency 6

Step 4: Serial Monitoring if Suppression Confirmed

• If adrenal suppression is confirmed, repeat testing at regular intervals (every 3 months initially, then every 6 months) with morning cortisol and ACTH levels and/or repeat ACTH stimulation testing to assess for recovery 1, 2
• More than 50% of patients with glucocorticoid-induced adrenal insufficiency show recovery, though timing varies significantly 3
• Some patients may have persistent suppression at 12 months or even 2 years 3

Critical Safety Considerations

During the Evaluation Period

• Patients must be educated on stress dosing (doubling doses during illness) and provided with emergency injectable steroids 2
• Medical alert bracelet for adrenal insufficiency is mandatory to trigger stress-dose corticosteroids by emergency medical services 1, 2
• Patients should be warned about signs of adrenal crisis: severe weakness, confusion, abdominal pain, hypotension 2, 7

Common Pitfalls to Avoid

• Do not attempt testing while on supraphysiologic doses of corticosteroids—results will be uninterpretable 1
• Do not abruptly discontinue steroids without confirming HPA axis recovery, as this risks life-threatening adrenal crisis 4, 5
• ACTH stimulation can give false-negative results early in the course of adrenal insufficiency; in cases of clinical uncertainty, opt for replacement and retest at 3 months 2
• Understanding the pretest probability of ACTH deficiency (the clinical background) is essential because diagnostic accuracy of ACTH stimulation testing is suboptimal in some contexts 6

Special Populations

Glucocorticoid-Induced Adrenal Insufficiency

• Approximately 50% of patients on ongoing oral glucocorticoid treatment or initially after withdrawal have adrenal insufficiency 4
• Higher maximum glucocorticoid doses significantly predict development of adrenal suppression 3
• Despite gradual taper, more than 50% of pediatric patients had persistent adrenal suppression after glucocorticoid discontinuation 3

Immune Checkpoint Inhibitor-Related Hypophysitis

• For patients with checkpoint inhibitor-induced hypophysitis, periodic assessment every 3 months in the first year, then every 6 months thereafter with clinical monitoring and repeat hormone levels (morning cortisol and ACTH and/or low-dose cosyntropin stimulation test) is recommended to assess recovery 1

Practical Algorithm Summary

1. Ensure clinical stability and readiness to potentially discontinue steroids
2. Consult endocrinology for long-term glucocorticoid exposure cases 1
3. Taper to physiologic doses (hydrocortisone 15-25 mg daily) 1, 2
4. Wait 4 weeks, then check morning cortisol 3
5. Discontinue glucocorticoids if clinically appropriate
6. Perform ACTH stimulation test to definitively assess HPA axis function 4, 6, 5
7. If suppressed: Continue replacement and retest every 3-6 months until recovery 1, 2
8. If normal: Patient can safely remain off steroids with appropriate education about stress dosing if needed in future 5