Glucocorticoid Replacement in Pituitary Surgery: Guidelines for Perioperative Assessment and Management

Abstract

Patients undergoing surgical resection of pituitary adenomas are frequently given perioperative glucocorticoid therapy. There are no randomized controlled studies assessing the need for such steroids; however, several studies have documented changes in the hypothalamic-pituitary-adrenal (HPA) axis associated with pituitary surgery. Based on the evidence available, this article details recommendations for the perioperative management of glucocorticoid therapy in patients with pituitary tumors. For patients with proven ACTH deficiency preoperatively [usually based on response to a short ACTH 1-24 (Synacthen) test], 48 hours of supraphysiological glucocorticoid therapy should be administered perioperatively (e.g. hydrocortisone, 50 mg every 8 hours on day 0, 25 mg every 8 hours on day 1, and 25 mg at 0800 h on day 2). For patients with intact HPA function preoperatively, and in whom selective adenomectomy is possible, perioperative glucocorticoids are not necessary. Early postoperative assessment depends on daily clinical assessment of the patient and 0800 h plasma cortisol levels. Cortisol levels over 450 nM (16 microg/dl) reflect normal HPA function, and levels less than 100 nM (3.6 microg/dl) are consistent with ACTH deficiency. Cortisol levels between 100 and 250 nM (3.6-9 microg/dl) may be ACTH deficient and should receive morning hydrocortisone replacement until definitive HPA axis testing. Cortisol levels between 250 and 450 nM (9-16 microg/dl) are unlikely to be ACTH deficient but should receive additional steroids for stress until a definitive test is performed. For those requiring definitive testing, the insulin tolerance test, the overnight metyrapone test, or the glucagon stimulation test are appropriate and may be performed as early as d 7-10 or, if more convenient, wk 4-6. Following the guidelines suggested here should reduce the use of unnecessary glucocorticoids, while ensuring the safety of patients is not compromised.

Immediate postoperative cortisol levels accurately predict postoperative hypothalamic–pituitary–adrenal axis function after transsphenoidal surgery for pituitary tumors

“…Previous studies of cortisol levels on postoperative days 3-7 have suggested that morning serum cortisol levels above 9-23 lg/dL may be predictive of an adequate stress response and normal HPA axis function [8,[22][23][24][25][26]. Data regarding predictive levels of serum cortisol on postoperative days 1-2 was previously limited by small sample size [27] and by reliance on multiple measures of cortisol levels [28], prompting us to investigate the utility of a single, 7 am cortisol level on the first postoperative day in predicting adequate stress response [11].…”

“…Patients with normal pre-operative HPA axis function did not receive glucocorticoid coverage during pituitary surgery [7,8,11]. All patients underwent an identical, modified low-dose CST at 4-6 weeks postoperatively using the same criteria for an adequate response.…”

“…Both doses of ACTH have been used to evaluate the HPA axis [3]. The low-dose test CST is more sensitive but less specific compared to standard dose CST test [4][5][6][7][8][9]. Neither is reliable for the diagnosis of acute ACTH deficiency within 2-4 weeks of an acute event [10], and therefore the utility of this assay during the immediate postoperative period is limited.…”

Postoperative assessment of the patient after transsphenoidal pituitary surgery

“…Treatment of all patients undergoing transsphenoidal pituitary surgery with peri-operative glucocorticoids is not universally undertaken. Some recommend administering these to patients with preoperative hypopituitarism [7] but withholding them in those with normal preoperative pituitary-adrenal function [peak cortisol [496.8 nmol/l (18 lg/dl) post 250 lg cosyntropin stimulation] in whom only selective adenomectomy is planned [7]. In one study of 83 patients without preoperative AI [ITT cortisol peak [ 510.6 nmol/L (18.5 lg/dl) and rise [270.6 nmol/l (10 lg/dl)] who did not receive peri-operative glucocorticoids, only one developed transient AI post-operatively [8].…”

Hypophysenvorderlappeninsuffizienz

“…Mehrere Studien weisen daraufhin, dass ein basales morgendliches Serumkortisol >450 nmol/l am 3. postoperativen Tag das Vorliegen einer sekundären NNR-Insuffizienz äußerst unwahrscheinlich macht [14]. Dies ist jedoch noch nicht ausreichend genug etabliert, um auf die definitive Testung 4-6 Wochen postoperativ zu verzichten.…”