Endoscopic Endonasal Surgery for Clinically Nonfunctioning Pituitary Adenomas

Background: Clinically nonfunctioning pituitary adenomas (NFPAs) are the most frequent pituitary macroadenomas, and represent approximately one-third of all pituitary adenomas. Patients often present with symptoms of mass effects, such as visual field defects, chronic headache, and hypopituitarism. Objective: The objective of this study was to retrospectively analyze the surgical results of 35 patients with non-functioning pituitary adenomas (NFPAs) operated by the endoscopic endonasal approach (EEA). Surgical outcomes including postoperative complications, recurrence and the postoperative visual and endocrine profile were assessed. Results: This retrospective study included 35 patients operated for clinically nonfunctioning pituitary adenomas (NFPAs) in Al Azhar university hospitals treated by endoscopic endonasal approach (EEA) in the last 6 years. 65.7% (n = 23) were male and 34.3% (n = 12) were female. The mean age was 41.5 (range 18 65) years. The most common presenting symptoms were headache, with 60% of the patients having headache. Visual disturbances were the presenting symptom in 82.9% patients and endocrinological problems (panhypopituitarism) were present in 6 (17.1%) patients. The number of patients suffering from cranial nerve deficit was 2 (5.7%). Visual acuity and visual field improved in 23 (79.3%) of 29 patients. The rate of tumor recurrence/regrowth was higher in the case of giant adenomas and cavernous sinus invasion represented 11 patients (31.4%). Conclusions: Early endoscopic endonasal approach surgery of NFPAs and effective surgical decompression reduces morbidity. Visual deficit improves in two third of cases. NFPAs represent high rate of recurrence due to invasion or incomplete resection especially with giant adenomas. The recurrence rate with growth total resection (GTR) is lower than subtotal resection (STR).


Introduction
Nonfunctioning pituitary adenomas (NFPAs) are the most common pituitary macroadenomas [1] [2] comprising 25% -40% of all pituitary neoplasms. Annual incidence is 1 new case per 100,000 of the population but their treatment and follow-up remains a difficult challenge [3]. Most NFPAs exhibit symptoms as a result of mass effect on adjacent structures such as the optic apparatus, the normal pituitary gland or stalk, or cranial nerves traversing the cavernous sinus [4] [5]. Endoscopic Endonasal Transsphenoidal Approach (EETA) is considered as the treatment of choice, and significant tumor debulking improves visual field disorders in 80% of patients and relieves headaches in almost every case [6]. However, even after complete or near complete surgical resection, NFMAs regrow in 12% -58% of patients within 5 years [7] [8].
For many years, microscopic trans-sphenoidal surgery (TSS) has been the standard of care. However, with the recent on-going advances in endoscopic visualization, endoscopic technology has been considered a major alternative [9].
At present transsphenoidal approaches are the most widely used techniques for the treatment of nonfunctioning pituitary adenomas. Suprasellar, parasellar extensions and cavernous sinus invasions of the tumors can be more effectively treated by endoscopic transsphenoidal approach that provides a better angle of vision. Previous studies have reported remission rates of 66% -93% for non-functioning pituitary adenomas that were treated by endoscopic transsphenoidal surgery [10] [11]. Furthermore, the rates of functional pituitary disorders have been reduced by preservation of normal pituitary gland by endoscopic techniques that have been increasingly used [12].
Limited illumination and smaller field of vision are disadvantages of the microscopic approach, whereas better illumination and visualization with a panoramic view with endoscopic approach are yet at the cost of two-dimensional images instead of three-dimensional; the latter approach allows a better extent of resection and bony exposure [13]. Endoscopic approach has better illumination and visualization with a panoramic view [14].

Patients and Methods
This study included 35 patients diagnosed with clinical NFMA (diameter > 10 mm on computed tomography (CT) scan or sellar magnetic resonance imaging (MRI) were operated with endoscopic endonasal transsphenoidal approach at Al Azhar university hospitals between 2014 and 2020 included in this retrospective study.
Our objectives are assessment visual, hormonal outcome and recurrence rate of non-functionning adenomas after endoscopic endonasal surgery.
Visual acuity, fundus examination and visual field (perimetry test) investigated pre-operative and post-operative at third and six month.
Preoperative pituitary hormone measurements were investigated in all patients. The hormone panel included cortisol, prolactin, ACTH, GH, IGF-1, LH/FSH, fT3, fT4, TSH, estradiol, progesteron, and testosteron levels. After surgical resection of their pituitary adenomas all patients were monitored for electrolytes and hormone levels postoperatively. Serum electrolytes and urine density were measured twice a day. Anterior pituitary hormone levels were also checked the next morning after surgery and at the third month post-operative.
All patients also underwent pre-operative Pituitary Magnetic Resonance Imaging (MRI sella with dynamic contrast study) and computed tomography (CT) on brain and paranasal sinuses with bone window study. Post-surgical all subjects underwent pituitary imaging follow-up study for at 3 months after surgery to check the tumor resection volume and repeated follow up MRI study after 6 months and each year for recurrence detection. All patients underwent surgery with pure endoscopic endonasal transsphenoidal approach. Concerning the adenoma size and extension, and structural anatomy of the nasal cavity, mononostril or binostril approach was preferred. Reconstruction of skull base was performed in a multilayer manner, using free fat and fascia lata grefts taken from the lateral side of thigh, fibrin tissue adhesive, and synthetic dura grafts as needed.

Results
A total of the 35 patients operated with endoscopic endonasal transsphenoidal approach for a nonfunctioning pituitary adenoma, 65.7% (n = 23) were male and 34.3% (n = 12) were female. The mean age was 41.5 (range 18 -65) years.
The most common presenting symptoms were headache, with 60% of the patients having headache together with other symptoms and 51.8% patients having headache alone. Visual disturbances were the presenting symptom in 82.9% patients and endocrinological problems (panhypopitutatrism) were present in 6 (17.1%) patients. The number of patients suffering from cranial nerve deficit was 2 (5.7%). Cerebrospinal fluid (CSF) leakage occurs in 5 cases representing (14.3%) three cases of them complaining from pneumocephalaus which need early interference by secondary repair to the sellar floor. Subtotal resection (STR) was achieved in 8 cases representing (22.9%) two cases of them presented by hematoma in the tumor bed leading to early post-operative worse visual outcome (Table 1).
Visual acuity and visual field examination (perimetry test) revealed that

Discussion
In the near past non-functioning pituitary adenomas were considered as poorly treatable disease, but nowadays considered as treatable disease with applying novel surgical approaches, and improved medical and radiotherapies. In this se- were studied. 67 (64%) patients were male. The low recurrent rate in our study related to the use of endoscopic approach which gross total resection can achieve in most cases rather than other microscopic approaches.
In our series growth total resection were achieved in 27 (77.1%) with recur-

Conclusion
Non-functioning pituitary adenomas are a challenge due to absent clinically hormonal manifestation and patient's later start to complain of visual problems in addition to headache. Early endoscopic endonasal approach surgery of NFPAs and effective surgical decompression reduces morbidity. Visual deficit improves in two third of cases. NFPAs represent high rate of recurrence due to invasion or incomplete resection especially with giant adenomas. The recurrence rate with growth total resection (GTR) is lower than subtotal resection (STR).