Adrenal Insufficiency and Adrenal Crisis in Cushing Disease

Pathophysiology of Increased Risk

The 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, according to the American College of Endocrinology 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, as stated by the Endocrine Society 1
This differs fundamentally from adrenalectomy for non-functional adenomas, pheochromocytomas, or aldosteronomas, where the HPA axis remains intact and functional, as noted by the European Association of Urology 2

Stress-dose glucocorticoid coverage is mandatory during and after adrenalectomy for Cushing disease because the suppressed HPA axis cannot respond to surgical stress, as recommended by the American Society of Anesthesiologists 1, 3
Major surgery requires hydrocortisone 2 mg/kg at induction followed by continuous IV infusion, with dosages varying by patient weight, as suggested by the Society of Pediatric Anesthesia 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, according to the American Association of Clinical Endocrinologists 1

Do not discontinue steroids too rapidly, as abrupt withdrawal can precipitate adrenal crisis—the taper must be gradual and guided by biochemical monitoring, as advised by the Endocrine Society 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, as warned by the American College of Physicians 1
Volume-resistant hypotension may be a late sign of adrenal crisis; earlier signs include non-specific malaise, somnolence, orthostatic hypotension, and persistent pyrexia, as noted by the European Society of Anaesthesiology 3

Serial morning cortisol monitoring is essential to guide steroid tapering and assess HPA axis recovery during follow-up, as recommended by the American Association for Clinical Chemistry 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, according to the European Society of Endocrinology 1