Recovery of the Hypothalamo-Pituitary-Adrenal Axis After Transsphenoidal Adenomectomy for Non-ACTH-Secreting Macroadenomas

J Clin Endocrinol Metab. 2019 Nov 1;104(11):5316-5324. doi: 10.1210/jc.2019-00406.

Abstract

Context: Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function.

Objective: To assess timing and predictors of HPA axis recovery after TSA.

Design: Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018.

Patients: Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA.

Main outcome measures: Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA.

Results: Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255).

Conclusion: HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / complications
  • Adenoma / metabolism
  • Adenoma / surgery*
  • Adolescent
  • Adrenal Insufficiency / etiology
  • Adrenal Insufficiency / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Male
  • Middle Aged
  • Neurosurgical Procedures / adverse effects*
  • Neurosurgical Procedures / methods
  • Pituitary Neoplasms / complications
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / surgery*
  • Pituitary-Adrenal System / physiopathology*
  • Postoperative Complications / metabolism*
  • ROC Curve
  • Recovery of Function
  • Retrospective Studies
  • Sphenoid Bone / surgery
  • Treatment Outcome
  • Young Adult

Substances

  • Hydrocortisone