Recovery of the hypothalamus-pituitary-adrenal (HPA) axis can occur as late as 12 months after transsphenoidal adenomectomy (TSA), according to study results published in The Journal of Clinical Endocrinology & Metabolism. These findings emphasize the need to periodically assess these patients to avoid unnecessary hydrocortisone replacement.
The primary treatment for most pituitary lesions is TSA. After pituitary surgery, the recovery of pituitary hormone deficits may be delayed; limited data are available regarding the postsurgical recovery of hormonal axes or predictors of recovery. The goal of this study was to assess HPA axis dysfunction and predictive markers of recovery following TSA, as well as time to recovery, to identify subgroups of patients who may be more likely to recover.
This single-center observational retrospective study enrolled 109 patients in the United Kingdom (71 men; mean age, 56 years; range, 17 to 82 years) who underwent TSA between February 2015 and September 2018 and had ≥1 reevaluation of the HPA axis with the short Synacthen (cosyntropin) test. The primary outcome was recovery of HPA axis function 6 weeks, 3 months, 6 months, and 9 to 12 months after TSA.
In 23 patients (21.1%), there was no evidence of pituitary hormone deficit before TSA. In 44 patients (40.4%), there was 1 hormone deficiency and in 25 patients (22.9%), preoperative evaluation showed >1 hormone deficiency.
Of the 23 patients with abnormal HPA function before surgery, 8 patients (34.8%) had recovered 6 weeks after the surgery. Patients who recovered were younger (mean age, 50±14 vs 70±9 years; P =.008) compared with patients who did not respond. Of the 15 remaining patients, 2 (13.3%) recovered at 3 months and 3 (20%) recovered at 9 to 12 months.
With regard to HPA function in the entire cohort 6 weeks after surgery, 32 patients (29.4%) did not pass the short Synacthen test. Of this group, 5 patients (15.6%) recovered at 3 months, 4 (12.5%) at 6 months, and 2 (6.2%) recovered 9 to 12 months after the surgery.
Predictors of future adrenal recovery at 6 weeks included having preoperative 30-minute cortisol >430 nmol/L (P <.001) and a day 8 postoperative cortisol >160 nmol/L (P =.001). With these cutoffs, 80% of patients with preoperative 30-minute cortisol >430 nmol/L (odds ratio [OR], 7.556; 95% CI, 2.847-20.055) and 80% of patients with day 8 postoperative cortisol >160 nmol/L (OR, 9.00; 95% CI, 2.455-32.989) passed the short Synacthen test at 6 weeks postsurgery. In addition, a 6-week baseline short Synacthen test cortisol level above or below 180 nmol/L (P <.001) predicted adrenal recovery at that time point.
None of the patients with all 3 variables below the aforementioned cutoffs recovered HPA axis within 1 year. On the other hand, 91.8% of patients with all 3 variables above those cutoffs had normal adrenal function at 6 weeks (OR, 12.200; 95% CI, 5.268-28.255).
In addition to the retrospective design, the study had other limitations, including the potential for selection bias, a heterogeneous patient cohort, and no data beyond 12 months after the surgery.
“[T]hese data offer the opportunity for patients who may have been given life-long replacement, to safely come off therapy and therefore avoid unnecessary glucocorticoid exposure,” wrote the researchers.
Pofi R, Gunatilake S, Macgregor V, et al. Recovery of the hypothalamo-pituitary-adrenal axis following transsphenoidal adenomectomy for non-ACTH secreting macroadenomas [published online June 21, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00406