Adrenal Insufficiency and Adrenal Crisis
Patients undergoing adrenalectomy for Cushing disease are significantly more likely to develop postoperative adrenal insufficiency and adrenal crisis compared to those undergoing adrenalectomy for other adrenal pathologies. This occurs because chronic hypercortisolism from Cushing disease suppresses the hypothalamic-pituitary-adrenal (HPA) axis, rendering the remaining adrenal tissue unable to produce adequate cortisol in response to surgical stress 1, 2.
Pathophysiology of Increased Risk
Removal of a cortisol-secreting adenoma in Cushing disease results in tertiary adrenal insufficiency because the HPA axis has been chronically suppressed by autonomous cortisol production 1.
The contralateral adrenal gland (or remaining tissue after unilateral adrenalectomy) cannot mount an adequate stress response immediately after surgery due to prolonged suppression of ACTH secretion 1.
This differs fundamentally from adrenalectomy for non-functional adenomas, pheochromocytomas, or aldosteronomas, where the HPA axis remains intact and functional 3, 4.
Clinical Evidence of Elevated Risk
The incidence of adrenal crisis after surgical treatment for Cushing syndrome is substantial at 9.0 crises per 100 patient-years 2.
All adrenal crises in one cohort study occurred while patients were on hydrocortisone replacement therapy, indicating that even with replacement, the risk remains elevated during the early postoperative period 2.
Adrenal crises tend to present early after remission of Cushing syndrome, during the period of severest HPA axis suppression, despite higher hydrocortisone replacement doses 2.
Patients who experience one adrenal crisis have a 2.3-fold increased risk of recurrent crisis 2.
Critical Management Requirements
Stress-dose glucocorticoid coverage is mandatory during and after adrenalectomy for Cushing disease because the suppressed HPA axis cannot respond to surgical stress 1, 3.
Major surgery requires hydrocortisone 2 mg/kg at induction followed by continuous IV infusion: 25 mg/24 hours for patients up to 10 kg, 50 mg/24 hours for 11-20 kg, 100 mg/24 hours for prepubertal patients over 20 kg, and 150 mg/24 hours for pubertal patients over 20 kg 1.
Once stable, patients should receive double the usual oral hydrocortisone doses for 48 hours, then reduce to normal replacement doses over up to a week 1.
Duration of Adrenal Insufficiency
Time to recovery of adrenal function is etiology-dependent and significantly longer in adrenal Cushing syndrome compared to other pathologies 5.
The probability of recovering adrenal function within 5 years is only 38% in adrenal Cushing syndrome versus 58% in Cushing disease and 82% in ectopic Cushing syndrome 5.
The median time to recovery in adrenal Cushing syndrome is 2.5 years (IQR 1.6-5.4 years), compared to 1.4 years in Cushing disease 5.
Common Pitfalls to Avoid
Do not discontinue steroids too rapidly, as abrupt withdrawal can precipitate adrenal crisis—the taper must be gradual and guided by biochemical monitoring 1.
Do not forget stress-dose coverage during intercurrent illness until HPA axis recovery is confirmed, as patients remain at risk for adrenal insufficiency during any physiologic stress 1.
Do not assume that patients on replacement therapy are protected from adrenal crisis—all crises in one study occurred despite hydrocortisone replacement 2.
Volume-resistant hypotension may be a late sign of adrenal crisis; earlier signs include non-specific malaise, somnolence, orthostatic hypotension, and persistent pyrexia 3.
Monitoring Strategy
Serial morning cortisol monitoring is essential to guide steroid tapering and assess HPA axis recovery during follow-up 1.
Regular endocrine follow-up is needed during the recovery phase to monitor for signs of adrenal insufficiency, guide steroid dose adjustments, and confirm HPA axis recovery before stopping replacement therapy 1.
Patients with additional pituitary hormone deficiencies may be at higher risk for adrenal crisis and require closer monitoring 2.