Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery:: a prospective controlled study

Background. We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors' institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. Method. Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. Findings. The urinary free cortisol excretion (UFC) in group A declined from 6732 +/- 7683 mu g/d on the day of surgery to 305 +/- 358 mu g/d on the 10(th) post-operative day. In group B, the respective UFC values were 12851 +/- 16278 mu g/d and 223 +/- 235 mu g/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 +/- 157 mu g/d on the day of surgery to 87 +/- 61 mu g/d on post-operative day six, reaching the normal range from the 2(nd) post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. Conclusions. The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent.