How to proceed with steroid therapy in a patient with a history of secondary adrenal insufficiency, currently presenting with bilateral avascular necrosis (AVN) of the hips, after stopping 5mg prednisolone (prednisolone) and having a morning cortisol level of 8.5?

Management of Steroid Therapy in Secondary Adrenal Insufficiency with AVN

You should permanently discontinue prednisolone and transition to physiologic hydrocortisone replacement at 15-20 mg daily in divided doses (10 mg morning, 5 mg afternoon), as her morning cortisol of 8.5 μg/dL after 48 hours off prednisolone indicates borderline adrenal function that requires continued but optimized glucocorticoid coverage. 1, 2

Rationale for This Approach

Why Stop Prednisolone

• Prednisolone is directly implicated in AVN development, particularly at doses ≥5 mg daily for prolonged periods, and continuing it will worsen her bilateral hip AVN and quality of life 3
• The combination of prednisolone plus bisphosphonates (zoledronate) creates additional AVN risk, making discontinuation critical for preventing further osteonecrosis 3
• Her morning cortisol of 8.5 μg/dL after 48 hours off prednisolone suggests partial HPA axis recovery but not complete sufficiency (normal is >10-15 μg/dL) 4

Why Hydrocortisone is Superior

• Hydrocortisone has significantly lower potency and shorter half-life than prednisolone, reducing cumulative glucocorticoid exposure and AVN risk while maintaining adequate adrenal coverage 1, 2
• Hydrocortisone 15-20 mg daily provides physiologic replacement without the supraphysiologic effects of 5 mg prednisolone (equivalent to 25 mg hydrocortisone) 5
• Divided dosing of hydrocortisone (larger morning dose, smaller afternoon dose) better mimics natural cortisol rhythm and reduces side effects 1, 2

Specific Management Algorithm

Immediate Actions (Next 1-2 Weeks)

1. Start hydrocortisone 10 mg upon awakening (before 9 AM) and 5 mg at 2 PM 1, 2
2. Educate patient on stress dosing: double the dose for 24-48 hours during minor illness, seek emergency care for severe illness 2
3. Provide emergency injectable hydrocortisone 100 mg IM with training on self-administration 2
4. Recommend medical alert bracelet for adrenal insufficiency 2

Follow-up at 2-4 Weeks

• Assess clinically for signs of under-replacement: fatigue, nausea, poor appetite, weight loss, hypotension 1, 2
• Assess for over-replacement: weight gain, insomnia, peripheral edema, hypertension 1
• Check blood pressure, weight, and serum electrolytes 2
• Do NOT rely on cortisol levels for monitoring adequacy—clinical assessment is primary 1

Dose Titration Strategy

• If symptoms of under-replacement occur, increase to 15 mg morning/10 mg afternoon (maximum 30 mg daily) 2
• If over-replacement signs develop, reduce to 10 mg morning/2.5 mg afternoon 2
• The goal is the lowest dose compatible with well-being, typically 15-25 mg total daily 2

Critical Considerations for HPA Axis Recovery

Testing for Recovery

• Perform ACTH stimulation test at 3 months to assess if HPA axis has recovered sufficiently to discontinue replacement 2, 4
• A cortisol response >18-20 μg/dL after 250 μg cosyntropin indicates adequate recovery 4
• Her current cortisol of 8.5 μg/dL suggests she may recover given only 2 years of 5 mg prednisolone exposure 4

Predictors of Recovery

• Mean prednisolone dose over the last 3 months is the best predictor of adrenal function, not total cumulative dose or duration 4
• Patients on lower doses (2.5-5 mg) have better recovery rates than those on higher doses 4
• Recovery can take weeks to years after stopping glucocorticoids 5

Important Pitfalls to Avoid

Common Errors

1. Never abruptly stop glucocorticoids after 2 years of therapy—this can precipitate adrenal crisis despite a cortisol of 8.5 μg/dL 3, 5
2. Do not continue prednisolone "because she feels fine"—AVN is progressive and will worsen with continued exposure, severely impacting mobility and quality of life 3
3. Do not use morning cortisol alone to guide therapy—clinical symptoms are more reliable than lab values 1

Adrenal Crisis Prevention

• Any physiologic stress (infection, surgery, trauma) requires immediate stress dosing: 100 mg hydrocortisone IV bolus, then 100 mg every 6-8 hours until recovered 2
• For dental procedures: extra morning dose 1 hour prior 2
• For major surgery: 100 mg IM before anesthesia, continue every 6 hours until oral intake resumes 2

Drug Interactions

• Anticonvulsants, rifampin, and barbiturates increase hydrocortisone requirements 1
• Grapefruit juice and licorice can potentiate glucocorticoid effects—advise avoidance 2

AVN-Specific Considerations

Why This Matters for Quality of Life

• Bilateral hip AVN at age 75 is devastating—it severely limits mobility, independence, and may require bilateral hip replacements 3
• Continuing prednisolone guarantees progression of AVN, while switching to lower-dose hydrocortisone may slow or halt progression 3
• The mortality and morbidity from AVN complications (immobility, surgical risks) far outweigh the theoretical risks of optimized glucocorticoid replacement 3

Bisphosphonate Consideration

• Do not give additional zoledronate while on any glucocorticoid—the combination increases AVN risk, particularly osteonecrosis of the jaw 3
• Once on stable low-dose hydrocortisone for 3-6 months with good bone health monitoring, bisphosphonates can be reconsidered if osteoporosis persists 3

Long-Term Plan

If ACTH stimulation test at 3 months shows adequate recovery (cortisol >18-20 μg/dL), attempt gradual hydrocortisone taper by 2.5 mg every 2-4 weeks while monitoring symptoms closely 4. If recovery is incomplete, continue physiologic hydrocortisone replacement indefinitely, as this provides adequate adrenal coverage with minimal AVN risk compared to prednisolone 2, 4.