Why is hydrocortisone (cortisol) prescribed after a pituitary resection?

Hydrocortisone After Pituitary Resection

Patients are placed on hydrocortisone after pituitary resection because the surgery can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, causing secondary adrenal insufficiency where the pituitary can no longer produce ACTH to stimulate cortisol production, and without cortisol replacement, patients risk life-threatening adrenal crisis characterized by cardiovascular collapse and shock. 1

Pathophysiology of Secondary Adrenal Insufficiency

• Pituitary surgery directly damages or removes ACTH-producing cells, leading to cortisol deficiency while aldosterone production remains intact (since aldosterone is controlled by the renin-angiotensin system, not ACTH). 1
• Without adequate cortisol during surgical stress, patients develop progressive loss of vasomotor tone and impaired alpha-adrenergic receptor responses to noradrenaline, progressing from orthostatic hypotension to supine hypotension and ultimately shock if untreated. 1
• The surgical stress itself dramatically increases cortisol requirements - normally the body produces 200-300 mg of cortisol daily during major surgery, far exceeding the typical 15-25 mg daily maintenance dose. 1

Perioperative Steroid Protocol

Intraoperative Management

• Administer hydrocortisone 100 mg intravenously at induction, followed by immediate initiation of continuous infusion at 200 mg per 24 hours for major surgery. 1
• Continuous IV infusion is superior to intermittent bolus dosing for maintaining physiologic cortisol concentrations during the stress response. 1, 2
• A recent study suggests that 50 mg intraoperatively may suffice for patients with intact HPA axis, though this remains controversial and the standard remains 100 mg. 3

Postoperative Management

• Continue hydrocortisone 200 mg per 24 hours by IV infusion while nil by mouth (alternatively, 50 mg every 6 hours intramuscularly). 1
• Once stable and taking oral medications, double the usual replacement dose (typically 20-10-10 mg hydrocortisone) for 48 hours, extending up to one week for complicated recovery. 1, 4
• Check morning cortisol 24 hours after stopping hydrocortisone - if >270 nmol/L (approximately 10 mcg/dL) in patients with preoperatively normal HPA axis, this indicates preserved axis integrity. 5, 3

Assessment of HPA Axis Recovery

Timing of Testing

• Morning cortisol should be checked on postoperative day 2 after the last hydrocortisone dose to determine if continued replacement is needed. 5, 3
• If morning cortisol is <10 mcg/dL, patients should remain on maintenance hydrocortisone and be retested at 6 weeks. 3
• Peak cortisol >550 nmol/L (approximately 20 mcg/dL) during insulin tolerance testing 5-8 days postoperatively is 100% sensitive and specific for predicting sustained HPA axis integrity. 5

Key Prognostic Indicators

• Lower preoperative morning cortisol levels (<9.3 µg/dL) are associated with 3-fold higher risk of postoperative adrenal insufficiency. 6
• For patients entering surgery with cortisol deficiency, an initial morning cortisol <60 nmol/L indicates sustained axis failure, while higher values require further testing. 5

Critical Pitfalls to Avoid

Medication Errors

• Never use dexamethasone alone for patients with suspected primary adrenal insufficiency - it completely lacks mineralocorticoid activity and cannot address electrolyte abnormalities. 1, 2
• Do not abruptly discontinue glucocorticoids - taper over 1-3 days as the precipitating illness resolves. 2
• Patients taking CYP3A4 inducers (rifampin, phenytoin, phenobarbital) may require higher hydrocortisone doses due to accelerated metabolism. 1, 4

Thyroid Hormone Considerations

• If multiple pituitary hormones are deficient, hydrocortisone must be replaced first before thyroid hormone to prevent adrenal crisis, as thyroid hormone accelerates cortisol metabolism. 7
• Wait at least one week after starting hydrocortisone before initiating thyroid hormone replacement. 7

Recognition of Adrenal Crisis

• Adrenal crises occur 6-8 times per 100 patient-years in patients with secondary adrenal insufficiency, with mortality rate of 0.5 per 100 patient-years. 1, 2
• Signs include severe weakness, persistent vomiting, hypotension, confusion, or collapse - treat immediately with hydrocortisone 100 mg IV bolus and 1 L isotonic saline over first hour. 2
• 8.6% of patients with chronic adrenal insufficiency report previous adrenal crisis caused by insufficient glucocorticoid medication during inpatient stays, often due to medication errors and omissions. 1

Emerging Evidence on Selective Steroid Use

• A 2022 randomized trial demonstrated that withholding hydrocortisone was noninferior to conventional supplementation in patients with intact preoperative HPA axis (11.0% vs 6.4% incidence of new-onset adrenal insufficiency, difference 4.6%, within 10% noninferiority margin). 6
• However, the no-hydrocortisone group still had 11% incidence of adrenal insufficiency, and given the life-threatening nature of adrenal crisis, routine prophylactic hydrocortisone remains the standard of care until better predictive tools identify which patients can safely avoid supplementation. 1, 6

Long-Term Management

• All patients discharged on glucocorticoid replacement should carry a steroid emergency card and wear medical alert identification. 4
• Provide hydrocortisone emergency self-injection kits (100 mg IM) for use during severe illness, vomiting, or inability to take oral medications. 4
• Educate patients on "Sick Day Rules": double glucocorticoid doses during illness, injury, or physiological stress. 4