Comparison of intraoperative cortisol levels after preoperative hydrocortisone administration versus placebo in patients without adrenal insufficiency undergoing endoscopic transsphenoidal removal of nonfunctioning pituitary adenomas: a double-blind randomized trial

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OBJECTIVE

In this double-blind randomized trial, the necessity of preoperative steroid administration in patients without adrenal insufficiency (AI) undergoing endoscopic transsphenoidal surgery (ETSS) for pituitary adenoma was evaluated.

METHODS

Forty patients with and without AI, defined as a peak cortisol level > 18 µg/dl on the insulin tolerance test or rapid adrenocorticotropic hormone (ACTH) test, undergoing ETSS for nonfunctioning pituitary adenomas were randomly allocated to treatment with either 100 mg of preoperative hydrocortisone (group HC, n = 20) or normal saline (group C, n = 20). The patients with pituitary apoplexy, the use of a drug within the last 3 months that could affect the hypothalamic-pituitary-adrenal axis, or a previous history of brain or adrenal surgery were excluded. Intraoperative cortisol and ACTH levels were measured after anesthesia induction, dura incision, and tumor removal, and at the end of surgery. Intraoperative hypotension, early postoperative AI, and postoperative 3-month pituitary function were investigated.

RESULTS

Intraoperative serum cortisol levels were significantly higher in the HC group than in the C group after anesthesia induction (median 69.0 µg/dl [IQR 62.2–89.6 µg/dl] vs 12.7 µg/dl [IQR 8.4–18.2 µg/dl], median difference 57.5 µg/dl [95% CI 33.0–172.9 µg/dl]), after dura incision (median 53.2 µg/dl [IQR 44.9–63.8 µg/dl] vs 6.4 [IQR 4.8–9.2 µg/dl], median difference 46.6 µg/dl [95% CI 13.3–89.2 µg/dl]), after tumor removal (median 49.5 µg/dl [IQR 43.6–62.4 µg/dl] vs 9.2 µg/dl [IQR 5.75–16.7 µg/dl], median difference 39.4 µg/dl [95% CI 0.3–78.1 µg/dl]), and at the end of surgery (median 46.9 µg/dl [IQR 40.1–63.4 µg/dl] vs 16.9 µg/dl [IQR 12.1–23.2 µg/dl], median difference 32.2 µg/dl [95% CI −42.0 to 228.1 µg/dl]). Serum ACTH levels were significantly lower in group HC than in group C after anesthesia induction (median 3.9 pmol/L [IQR 1.7–5.2 pmol/L] vs 6.9 pmol/L [IQR 3.9–11.9 pmol/L], p = 0.007). No patient showed intraoperative hypotension due to AI. Early postoperative AI was observed in 3 and 5 patients in groups HC and C, respectively. The postoperative 3-month pituitary hormone outcomes including ACTH deficiency were not different between groups.

CONCLUSIONS

Preoperative steroid administration may be unnecessary in patients without AI undergoing ETSS for nonfunctioning pituitary adenomas. However, a further large-scale study is needed to determine whether preoperative steroid administration has a significant impact on clinically meaningful events such as perioperative AI and postoperative 3-month ACTH deficiency in these patients.

Korean Clinical Trial Registry no.: KCT0002426 (https://cris.nih.go.kr/cris/).

ABBREVIATIONS ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; ETSS = endoscopic transsphenoidal surgery; GH = growth hormone; GN = gonadotropin; HPA = hypothalamic-pituitary-adrenal; HR = heart rate; ICU = intensive care unit; NFPA = nonfunctioning pituitary adenoma; PONV = postoperative nausea and vomiting; SBP = systolic blood pressure; TSH = thyroid-stimulating hormone.
Article Information

Contributor Notes

Correspondence Hee-Pyoung Park: Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea. hppark@snu.ac.kr.INCLUDE WHEN CITING Published online January 24, 2020; DOI: 10.3171/2019.11.JNS192381.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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