What is the recommended prednisone taper regimen for patients undergoing adrenalectomy?

Prednisone Taper After Adrenalectomy

For patients undergoing adrenalectomy for Cushing syndrome, initiate stress-dose hydrocortisone 100 mg IV at induction followed by 200 mg/24h continuous infusion, then transition to oral prednisone 20 mg daily (or hydrocortisone 50 mg daily in divided doses) and taper gradually over weeks to months based on ACTH recovery. 1, 2

Immediate Perioperative Management

Intraoperative Coverage

• Administer hydrocortisone 100 mg IV at surgical induction 1
• Follow immediately with continuous infusion of hydrocortisone 200 mg/24h (or alternatively hydrocortisone 50 mg IV/IM every 6 hours) 1

Early Postoperative Period (Days 1-2)

• Continue hydrocortisone 200 mg/24h IV infusion while NPO or unable to tolerate oral intake 1
• Transition to oral therapy once tolerating PO: hydrocortisone 30-50 mg daily in divided doses (2/3 morning, 1/3 early afternoon) OR prednisone 20 mg daily 1, 3

Oral Taper Protocol

Conversion and Dosing

• Use the equivalency ratio: 20 mg hydrocortisone = 5 mg prednisone 1, 4
• Initial oral replacement: prednisone 20 mg daily OR hydrocortisone 50 mg daily (divided as 30 mg AM, 20 mg early afternoon) 1, 3
• Administer morning doses before 9 AM to align with physiologic cortisol rhythm 5

Taper Schedule

• Days 2-7 post-op: Continue double-dose replacement (prednisone 20 mg daily or hydrocortisone 50 mg daily) 1
• Week 2-4: Reduce to standard replacement doses (prednisone 10-15 mg daily or hydrocortisone 30-40 mg daily in divided doses) 1, 3
• Months 1-6: Gradually taper by 2.5-5 mg prednisone (or 5-10 mg hydrocortisone) every 2-4 weeks based on clinical response and ACTH levels 3
• Goal: Reach physiologic replacement of prednisone 5 mg daily (or hydrocortisone 15-20 mg daily) 1, 4

Monitoring During Taper

Clinical Assessment

• Monitor for signs of under-replacement: fatigue, nausea, hypotension, hyponatremia, hyperkalemia 1, 6
• Monitor for signs of over-replacement: bruising, thin skin, edema, weight gain, hypertension, hyperglycemia 1, 4
• Check morning ACTH and cortisol levels every 2-4 weeks during taper 1, 3

Laboratory Targets

• ACTH should normalize (not remain suppressed) as taper progresses 3
• Morning cortisol >3 mcg/dL suggests some adrenal recovery; <3 mcg/dL indicates continued need for replacement 1
• Consider ACTH stimulation test if cortisol 3-15 mcg/dL to assess adrenal reserve 1

Special Considerations by Indication

Cushing Syndrome (Requires Replacement)

• All patients with Cushing syndrome (overt or subclinical) require postoperative steroid replacement 2
• This includes: adrenal adenomas, ectopic ACTH tumors, pituitary-dependent disease after failed pituitary surgery, and subclinical Cushing from incidentalomas 2
• Expect prolonged taper (3-12 months) as the contralateral adrenal recovers from chronic suppression 2, 3

Bilateral Adrenalectomy

• Requires lifelong glucocorticoid replacement 2, 7
• Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement (primary adrenal insufficiency) 1, 4
• Titrate fludrocortisone based on volume status, sodium, and renin (target upper half of reference range) 1

Unilateral Adrenalectomy for Non-Cushing Disease

• No steroid replacement required 2
• This includes pheochromocytoma, non-functioning adenomas, and other non-Cushing pathology 2
• Zero cases of adrenal insufficiency reported in this population 2

Critical Pitfalls to Avoid

Adrenal Crisis Risk

• 7% of patients on replacement therapy develop acute adrenal insufficiency during taper 2
• Educate patients on stress-dosing: double or triple maintenance dose during illness, injury, or stress 1, 4
• Provide emergency injectable hydrocortisone and medical alert identification 1, 4
• Never abruptly discontinue steroids—always taper gradually 5

Timing Considerations

• Staged bilateral procedures reduce immediate steroid dependence compared to simultaneous bilateral surgery (40% vs 86% requiring replacement at discharge) 7
• Intervening before tumors reach 4 cm reduces long-term steroid dependence (18% vs 75%) 7
• Prednisolone has plasma half-life of 5.5 hours, remaining detectable for ~48 hours after dosing 8

Hydrocortisone vs Prednisone Choice

• Hydrocortisone preferred for physiologic replacement due to shorter half-life allowing diurnal rhythm recreation 1, 4
• Hydrocortisone shows advantages in improving liver function post-adrenalectomy 3
• Prednisone acceptable alternative with lower risk of edema and potentially faster taper completion 3
• Prednisone may cause more HPA axis suppression due to longer duration of action 5

Drug Interference

• Stop prednisone at least 48 hours before measuring cortisol levels (cross-reacts in most assays) 8
• Dexamethasone should NOT be used for long-term replacement (lacks mineralocorticoid activity and causes prolonged suppression) 9