Perioperative Steroid Management for MACS Patients Undergoing Adrenalectomy
Yes, patients with MACS undergoing adrenalectomy require perioperative glucocorticoid coverage, with the specific protocol depending on whether they have established adrenal insufficiency or are at risk for developing it postoperatively.
Intraoperative and Immediate Postoperative Management
For adrenalectomy (major surgery), you should provide full stress-dose steroid coverage:
- Intraoperatively: Hydrocortisone 100 mg IV at induction, followed immediately by continuous infusion of hydrocortisone 200 mg/24 hours 1
- Postoperatively: Continue hydrocortisone 200 mg/24 hours IV infusion while NPO (alternatively, hydrocortisone 50 mg IM every 6 hours) 1
- Once tolerating oral intake: Resume enteral glucocorticoids at double the usual replacement dose for 48 hours, extending up to one week for major surgery 1
Rationale for Full Coverage
The UK guidelines for perioperative glucocorticoid management specifically address patients with adrenal insufficiency undergoing major surgery 1. While these guidelines don't explicitly mention MACS, the physiologic principle is clear: normal cortisol production increases five-fold (to ~100 mg/day) during major surgery 1. Patients with MACS have suppressed hypothalamic-pituitary-adrenal (HPA) axis function and cannot mount this stress response, making them functionally similar to patients with established adrenal insufficiency during the perioperative period.
Postoperative Assessment and Weaning Strategy
The critical decision point occurs on postoperative day 1 when you must determine the duration of steroid replacement:
Day 1 Assessment Protocol
Obtain both tests for optimal decision-making:
- Morning (AM) serum cortisol level
- ACTH (cosyntropin) stimulation test if cortisol is borderline
Interpretation Algorithm
Postoperative steroid replacement is needed if:
- POD 1 cortisol <5 μg/dL: Definite need for replacement 2
- POD 1 cortisol <10 μg/dL AND failed ACTH stimulation test (peak <18 μg/dL): Need for replacement 2, 3
- Clinical symptoms of adrenal insufficiency: Regardless of lab values 2
Steroid replacement can be avoided if:
- POD 1 cortisol ≥10 μg/dL AND normal ACTH stimulation test (peak ≥18 μg/dL)
Important Nuance on Testing
Recent multicenter data shows that basal cortisol and ACTH stimulation tests are discordant in 22% of patients, with higher discordance (32%) in those with bilateral nodules 3. Therefore, performing both tests postoperatively is recommended rather than relying on basal cortisol alone.
Predictors of Postoperative Adrenal Insufficiency
Preoperative Risk Factors
The strongest independent predictors that a MACS patient will need postoperative steroids are:
- Cortisol >4.2 μg/dL on 1 mg dexamethasone suppression test (P = .008) 2
- Plasma ACTH <7.0 pg/mL (P = .02) 2
- Younger age (OR 0.67 per 10 years) 3
- Higher biochemical severity scores 3, 4
Expected Incidence
Approximately 50-54% of MACS patients develop postoperative adrenal insufficiency requiring replacement 3, 4. This is substantially higher than the 14% rate seen with true non-functioning adenomas 4, but lower than the 72% rate with overt Cushing's syndrome 4.
Duration of Replacement Therapy
Median recovery time is 3.9 months (IQR 3-5.9 months) 3, but this varies by severity:
- Mild MACS: 3 months
- Moderate MACS: 4-5 months
- Severe MACS: 12-14 months 3
The median weaning time in one large series was 78 days (IQR 35-251 days) 2.
Follow-up Testing Schedule
- Serial cortisol testing at 3-month intervals is recommended 4
- Continue replacement until morning cortisol >10 μg/dL or normal ACTH stimulation test
- Some patients may require replacement for up to 35 months 4
Critical Clinical Pitfalls
Common Mistake #1: Assuming All MACS Patients Need Long-term Replacement
Using the algorithm above, only 23% of MACS patients in one large series actually required postoperative steroids 2, contradicting earlier assumptions that most would need replacement. The key is objective postoperative testing rather than empiric prolonged treatment.
Common Mistake #2: Using DST Cutoff Alone
Patients with DST 1.8-5 μg/dL (mild MACS) had significantly higher postoperative cortisol levels (8.0 vs 5.0 μg/dL), were less likely to need replacement (59% vs 89%), and had shorter treatment duration (4.4 vs 10.7 months) compared to those with DST >5 μg/dL 5. Don't automatically assume all MACS patients are equivalent—severity matters.
Common Mistake #3: Skipping Perioperative Coverage
While some patients ultimately won't need long-term replacement, you cannot predict this preoperatively with certainty. The stress of major surgery requires full coverage initially 1. The distinction between "needs perioperative coverage" (yes, all MACS patients) and "needs long-term replacement" (only ~50%) is crucial.
Common Mistake #4: Not Testing Patients with Bilateral Nodules
Patients with bilateral adrenal nodules have higher rates of discordant test results (32% vs 19%) 3. In these cases, both basal cortisol and ACTH stimulation testing are particularly important to avoid misclassification.
Contrast with Non-MACS Patients
For context, patients undergoing unilateral adrenalectomy for non-Cushing adrenal disease do not require any steroid replacement 6. This underscores that MACS represents a distinct intermediate category requiring individualized assessment based on the algorithm above.