Pituitary Gland Endocrine Outcomes from a Prospective Multicenter Study of Fully Endoscopic Transsphenoidal Surgery for Adults with Nonfunctioning Pituitary Adenomas

Introduction: To date, no prospectively obtained pituitary hormone outcomes data are available for patients who have undergone fully endoscopic pituitary surgery using modern gland-sparing surgery techniques. Current data are limited to single-center, often single-surgeon, retrospective case series. In this report, we analyze the 6-month anterior and posterior pituitary endocrine outcomes from a multicenter prospective study of adults with surgically treated clinically nonfunctioning adenomas (ClinicalTrials.gov NCT02357498).

Methods: Patients underwent preoperative and 6-month endocrine evaluation by a multidisciplinary team. All patients underwent fully endoscopic transsphenoidal surgery. Routine hormone testing was performed and reported according to Fatemi et al (2008). Adrenal, thyroid, gonadal, posterior gland functions were evaluated. Growth hormone results are not presented due to the limited use of confirmatory stimulation testing in this study and the practical challenges of prescribing replacement therapy. Changes in function for each pituitary-axis were classified as “unchanged” (i.e., normal hormone function preoperatively and postoperatively), “recovered” (i.e., preoperative hypopituitarism that resolved after surgery and no hormone supplementation needed), “persistent hypopituitarism” (i.e., hypopituitarism present before surgery and at 6 months), and “new deficiency” (i.e., development of new hypopituitarism after surgery). The data were analyzed by a biostatistician affiliated with the lead institution.

Results: A total of 177 patients were treated with endoscopic transsphenoidal surgery at 6 US pituitary centers by 11 surgeons from February 2015 to June 2017. A total of 169 (95.5%) patients were available for follow-up. Of 169 patients, 95 (56.2%) had a preoperative deficiency in at least 1 hormone axis. 14/169 (8.3%) patients developed at least one new deficiency and 20/93 (21.5%) noted recovery in at least one axis at follow-up. 93/169 (55.0%) had a deficit in at least one axis at follow-up.

For adrenal function, 9/31 (29.0%) recovered and 4/135 (3.0%) developed a new deficiency. For thyroid function, 8/72 (11.1%) recovered and 6/97 (6.2%) developed a new deficiency. For male hypogonadism, 5/50 (10.0%) recovered and 3/49 (6.1%) developed a new deficiency. Finally, for posterior gland function, 4/166 (2.4%) developed permanent diabetes insipidus.

Larger tumor size (p = 0.022) was an independent predictor of postoperative hypopituitarism. The mean preoperative tumor volume in patients with no hormone deficiency at 6 months was 5.6 ± 3.6 cm³ compared with 8.4 ± 6.7 cm³ in the group with a hormone deficiency (p = 0.001). Notably, surgical goal (i.e., attempted complete vs. subtotal tumor removal) and actual extent of tumor removal were not predictive of endocrine outcome (p > 0.11).

Conclusion: This is the first multicenter prospective study of fully endoscopic pituitary surgery to report pituitary hormone outcomes; the results of this study can serve as benchmark outcomes in patients with surgically treated nonfunctioning adenomas. A substantial minority of patients experience restoration of gland function in at least one axis after surgery possibly due to relief of gland compression by tumor.