Endoscopic Endonasal Transsphenoidal Approach for Growth Hormone Secreting Pituitary Adenoma

INTRODUCTION

Pituitary neoplasms are benign tumors and mainly originate from adenohypophysis, classi‌fied differently according to their size or endo‌crine function. Pituitary microadenomas are defined as a group tumor of less than one cen‌timeter in diameter, correspondingly all the oth‌ers greater than acetimeter  in diameter are called as pituitary macroadenomas.¹

Except for prolactinoma, pituitary adenomas account for 10-22.5 percent of all primary intracranial tumors, and surgical excision is the first choice for treatment. ²

Suppression of hormone hypersecretion, decrease of tumor bulk, maintenance of normal pituitary function, avoidance of long-term consequences from excess hormone secretion, and avoidance of tumor recurrence are all aims in the treating of those with pituitary lesions. ³

The majority of pituitary adenomas occur in the anterior lobe of the pituitary gland and may be removed selectively with transsphenoidal adenomectomy, preserving pituitary function while eliminating the tumor. Some adenomas, on the other hand, develop inside the pituitary stalk and stay there. Other adenomas of the pituitary gland originate in the upper section of the anterior lobe and spread into the stalk. ⁴

Acromegaly is a dangerous condition that, if left untreated, is linked to a higher likelihood of morbidity and death.

Adenomas of the pituitary gland that secrete growth hormone (GH) cause acromegaly. GH hypersecretion may cause a variety of symptoms and indications, ranging from acral overgrowth and soft tissue edema to diabetes and heart failure. This presentation may include visual field abnormalities and headaches as a result of the growing tumor. ⁵

During transsphenoidal pituitary surgery, neurosurgeons can now see obscure anatomical corners thanks to the use of endoscopes. ⁶

Since 1997, one of the most considerable advances in the treatment of pituitary lesions has been the advancement of the endonasal endoscopic procedure for the resection of pituitary adenomas. The procedure has expanded around the globe and is currently the standard surgical treatment for sellar lesions in many neurosurgery facilities. ⁷

The goal of the research was to see how an endoscopic transnasal transsphenoidal technique for a growth hormone-secreting pituitary adenoma affected hormonal decrease in relation to surgical excision extent.

PATIENTS AND METHODS

From September 2019 to August 2021, retrospective and prospective research was conducted on fifteen (15) patients who were operated on at the neurosurgery department at Al Azhar University Hospital "Al-Hussein" and "Bab El-Shaeria.". In this study, all Patients had been diagnosed as Growth Hormone secreting Pituitary lesion and underwent Endoscopic Endonasal Trans sphenoidal Procedure, assessed and evaluated as for preoperative, intraoperative, and postoperative. Neurological, endocrinological and radiological evaluations were assessed preoperatively as well as after surgery. This study covered all patients who had endoscopic endonasal transsphenoidal Procedure for Growth Hormone Pituitary Tumors. Before the trial, all patients completed an informed consent form.

The exclusion criteria: Patients with recurrent tumor, patients unfit for surgery, failure of pneumatization of sphenoid sinus and Patients with history of Radiotherapy.

Ethical considerations: All the necessary approvals for carrying out the research were obtained. An official approval for implementation of the study was obtained from Neurosurgery department before starting the study. The Ethical Committee of Al-Azhar University's Faculty of Medicine gave its approval to the research.

Methods

Preoperative Evaluation: All patients were submitted to the following items: Full history taking, Examination: included general, neurological examination and ophthalmological evaluation, Endocrinological assessment: (pre-operative hormonal profile) Lab. assessment (GH, IGF1, Prolactin, FSH, LH, ACTH, TSH, cortisone, T3, T4, and Testosterone, Estradiol). These hormonal assessments were repeated 3 months post operative during the follow up. Radiological assessment: Pre-operative MRI with contrast, CT sella and para nasal sinuses, Assessment of fitness for surgery by an anesthesiologist and all patients who included were fit. All patients were informed about the surgical techniques, the likelihood of failure, and the necessary after care. All patients signed a written permission form.

Surgical technique: Anesthesia, positioning and draping: To establish a normotensive state with a low pulse rate, general anesthesia with total intravenous anesthesia (TIVA) is used. Operative procedures: Nasal phase: The endoscope was placed into the nostril parallel to the MT, in line with the floor of the nasal canal, to see the choana first, then the anterior wall of the sphenoid.  Sphenoidal phase : After palpating the sphenoid ostium using a blunt dissecting tool, it was opened. With angled punches, the front wall of the sphenoid was opened wide. To improve exposure, a tiny portion of the posterior nasal septum was removed. Sellar phase and removal of the tumor: A dissector was used to open the sella's floor, followed by Kerrison upcutting forceps. The size of the aperture is determined by the size of the sella and the distance between the two carotid arteries, but it should be big enough to allow for tool insertion and provide a clear view of the adenoma for removal. The pituitary gland was discovered by the neurosurgeon during surgery. The dura was incised in a linear or cruciate pattern in the midline. In individuals with macroadenomas, the superior and inferior intercavernous sinuses were generally squeezed and destroyed, rendering the dural incision bloodless.

The excision of macroadenomas was carried out in stages. Before the upper aspect of the lesion was excised, the inferior and lateral pieces were eliminated. Sellar reconstruction: The goal of this procedure was to provide a watertight seal, eliminate dead space, and inhibit the chiasm from descending into the sellar cavity. Nonetheless, excessive packing must be avoided to avoid optic system compression. In rare situations, sellar packing was done using gel foam and fibrin glue.

Postoperative follows up: Antibiotics as a preventative measure Serial visual examination and monitoring of endocrine functions (post-operative hormonal profile) and metabolic state were part of the postoperative follow-up. The majority of patients were released on the second or third postoperative day, with frequent outpatient clinic follow-up (follow-up protocol: one week, one month, three months, six months), and home therapy maintained if necessary. On the second day following surgery, a follow-up MRI was performed. Every patient's case sheet was filled with the required information. The study's biggest flaw was the small number of instances it included. This research also had a brief follow-up procedure. The study's findings were obtained by statistical analysis of the gathered data.

Fig. 1: various steps of the approach and tumor resection (a) nasal phase (b) sphenoidal phase (c) sellar phase (d) removal of sellar bone part (e) removal of pituitary tumor

RESULTS

Demografic Data:

Tabe (1) 15 patients were joined in this research, 8 males (53.3%) and 7 females (46.7%), between ages of 19 to 64 years the median age of all analyzed patients was 41.3 ± 16.07 years underwent endoscopic endonasal transsphenoidal surgery.

Table 1: Demographic characteristics of all patients included in the study

Clinical presentation:

Table (2) shows the description of clinical presentation in all studied patients. Acromegaly features was presented in 15 patients (100%), headache was presented in 11 patients (73.3%), menstrual irregularity was presented in 3 patients (20%) and visual impairment was presented in 10 patients (66.7%).

Table 2: Clinical presentation of all individuals investigated

Radiology:

Table (3) shows the description of pre-operative radiological examination in all studied patients. As regardvolume, it was macro-adenoma in all studied patients (100%). As regard Cavernous Sinus Invasion, it was occurred in 6 patients (40%) of the studied patients. As regard extension, it was localized to Sella in 8 patients (53.3%) and Supra Sellar extension in 7 patients (46.7%).

Table 3: Description of pre-operative radiological examination in all studied patients.

Surgical excision of the tumor:

Table (4) shows the description of surgical excision in all investigated patients. It was Total excision in 12 patients (80%) and Subtotal excision in 3 patients (20%).

Table 4: Description of surgical excision in all investigated patients

Operative time and Hospital stay:

Table (5) shows the description of operative time & post-operative hospital stay in all studied patients. As regard operative time, the mean operative time of all studied patients was 165.2 ± 12.7 min with minimum operative time of 145 min and maximum operative time of 187 min. As regard post-operative hospital stay, the mean stay of all studied patients was 5.9 ± 0.8 days with minimum stay of 5 days and maximum stay of 7 days.

Table 5: Description of operative time & post-operative hospital stay in all studied patients

Pre and post Hormonal profile:

Next table shows Highly statistically significant (p-value < 0.001) decreased post-operative growth hormone (3.4 ± 1.2) when compared with pre-operative growth hormone (38.1 ± 29.8). Highly statistical significant (p-value < 0.001) decreased post-operative IGF-1 (242.3 ± 102.1) when compared with pre-operative IGF-1 (665 ± 253). No statistical substantial variance (p-value > 0.05) between pre-operative and post-operative the following hormones (ACTH, cortisol, T3, T4, TSH, testosterone, E2, FSH, LH and PRL).

Table 6: Comparison of pre-operative and post-operative hormonal profile in studied patients

T: independent sample T test.            

HS: p-value < 0.001 highly substantial.

MW: Mann Whitney U test.                               

NS: p-value > 0.05 is non- substantial.

Case sample

male patient 50 years old presented with Acromegalic features, headache, chest pain of 4 years duration,Hormonal assay pre: GH(36.1 ng/ml) IGF1 (463 ng/ml),Hormonal assay post: GH(4.67 ng/ml) IGF1( 130 ng/ml),Fundus examination: bilateral normal fundi,Operation:puree ndoscopic endonasal trans sphenoidal surgery.

Fig. : (A) Preoperative, sagittal and coronal contrast-enhanced T1-weighted MR images of a case of GH secreting pituitary adenoma (B) Postoperative sagittal and coronal T1-weighted MR images of a case of GH secreting pituitary adenoma after gross total Resection.

DISCUSSION

Surgical excision alone has been demonstrated to be beneficial in managing illness in up to 80% of patients with microadenomas and 50% of patients with macroadenomas, with up to 65% of patients experiencing long-term disease control. Surgery is often coupled with postoperative medicinal treatment, which may include somatostatin receptor ligands (SRL), GH-receptor antagonists, dopamine agonists (DA), and radiation in situations of resistant or persistent illness. ⁵

ETPS is quickly supplanting both open transcranial and transsphenoidal microscope-based procedures for pituitary adenomas removal.

In terms of demographic data for all patients analyzed, our findings indicated that the median age of all patients was 41.3± 16.07 years, with a median age of 19 years and a maximum age of 64 years. In terms of gender, there were eight men (53.3%) and seven females (46.7%) among the patients investigated.

The current research, which was funded by Unal et al.,⁸ sought to evaluate the outcomes of the transsphenoidal endoscopic technique for acromegaly and to identify predictors of remission. 73 individuals were involved in the trial, all of whom had surgery through the transsphenoidal endoscopic technique. There were 38 male (52.05%) and 35 female (50.75%) patients, with an average age of 49.3 years (range, 30–79 years).

Additionally, Aydin et al.,⁹ conducted an  endoscopic transsphenoidal procedure for acromegaly is being studied to see how effective it is. 106 individuals with acromegaly were included in the trial and underwent endoscopic endonasal transsphenoidal technique. There were 56 females (58.9 percent) and 39 males (41.1 percent), with an average age of 43.4 ±12.4 (range 16–79) years.

Additionally, Babu et al.,¹⁰ sought to examine long-term remission rates in individuals with acromegaly after endoscopic transsphenoidal procedure and to connect these rates with genetic and radiographic indicators of disease aggressiveness. 58 individuals were recruited in the trial, all of whom underwent endoscopic endonasal transsphenoidal technique. 29 females and 29 men were present, ranging in age from 20 to 72 years (median 48.6 13.4 years).

In the current study regarding the pre-operative radiological examination in the studied patients we found that all studied patients (100%) had macro-adenoma. As regard Cavernous Sinus Invasion, it was occurred in 6 patients (40%) of the studied patients. As regard extension, it was localized to Sella in 8 patients (53.3%), and Supra Sellar extension in 7 patients (46.7%).

However, the study by Unal et al.,⁸ reported that there were 57 macroadenomas (78%) and 16 microadenomas (22%) were surgically treated. The mean tumor volume was 2,073 mm3. Four patients had giant macroadenomas (>4>cm). Cavernous sinus invasion was detected in 32 (43.83%) of the 73 patients. Eighteen patients (24.6%) had a significant optic chiasm compression.

Also, the study by Aydin et al., ⁹ showed that Pituitary macroadenomas were found in 69 (72.6%) of the patients, with 12 (12.6%) of these being gigantic adenomas (4 cm). In 32 (33.6%) of the patients, suprasellar extension was seen. In 19 (20%) of the patients, preoperative sellar MRIs indicated Knosp Grade 3 or 4 cavernous sinus invasions.

As well, the study by Babu et al.,¹⁰ reported that A total of 21 microadenomas and 37 macroadenomas were found. The tumor volume was 3.2 ±5.3 cc on average. There were 15 (25.8%) Knosp grade 0 tumors (entire tumor medial to the medial carotid tangent), 20 (34.4%) Knosp grade 1 cancers (cancer medial to the median carotid tangent), 12 (20.7%) Knosp grade 2 cancers (cancers medial to the lateral carotid tangent), 4 (6.8%) Knosp grade 3 cancers (cancers lateral to the (tumors encircling the carotid arteries).

Furthermore, Cardinal et al.,¹¹ reported that the median lesion diameter at presentation was 1.6 cm (IQR 1.1–2.3 cm); 10 lesions (19%) were microadenomas, and 42 (81%) were macroadenomas. On preoperative MRI, suprasellar extension was found in 18 patients (35%), infrasellar invasion in 40 patients (77%), and cavernous sinus invasion in seven patients (13 percent).

In the present study regarding clinical presentation in the studied patients, we found that acromegaly features were presented in 15 patients (100%), headache was presented in 11 patients (73.3%), menstrual irregularity was presented in 3 patients (20%) and visual impairment was presented in 10 patients (66.7%).

However, the study by Cardinal et al.,¹¹ reported that The majority of the patients (96%) had dysmorphic craniofacial traits, with 37 (71%) having larger rings or feet, 13 (25%) having skin tags, and 10 (19%) having excessive sweating. 25 (48 percent) of individuals with dysmorphic craniofacial traits had prognathism, 22 (42 percent) had frontal bossing, and 17 (32 percent) had macroglossia.

Also, Leopoldo et al.,¹² 23 acromegaly patients were recruited and underwent endoscopic transsphenoidal surgery. All of the patients had clinical indicators of acromegaly. Reduced visual acuity or visual fields, headaches, and bone and joint discomfort plagued around half of these individuals.

As well, Yano et al.,¹³ enrolled Endoscopic transsphenoidal surgery was performed on 47 acromegalic individuals. Acromegalic characteristics were seen in 44 individuals (93.6%), and 13 patients had visual impairments. One patient merely had a headache when he came in.

In relation to the description of surgical excision in all individuals investigated. In 12 cases (80%), entire excision was performed, while in three individuals, subtotal excision was performed (20 percent).

However, the study by Aydin et al.,⁹ showed that there was subtotal excision in 76 patients (80%) and total excision in 19 patients (20%).

While, the study by Cardinal et al.,¹¹ reported that Sixty-six patients (69%) had gross-total resection (GTR; average maximum tumor diameter 1.47 cm), while sixteen patients (31%) had subtotal resection (STR; mean maximal tumor diameter 2.74 cm).

Regarding the operative characteristics, we found that the mean operative time of all studied patients was 165.2 ± 12.7 min with minimum operative time of 145 min and maximum operative time of 187 min. As regard post-operative hospital stay, the mean stay of all studied patients was 5.9 ± 0.8 days with minimum stay of 5 days and maximum stay of 7 days.

The study by Hofstetter et al.,¹⁴ analyzed 24 endoscopic transsphenoidal surgeries and reported that the endoscopic transsphenoidal surgeries lasted a median of 182 minutes (range 104–326 minutes) and the mean hospital stay was 3.6 ± 1.8 days.

Also, the study by Shin et al.,¹⁵ In this research of 53 patients, 42 (79.2%) had gross entire resection and 11 (20.8%) had near whole resection (90–99 percent resection). Subtotal resection was not performed on any of the patients. The study reported that the mean operative time was (3:42 hours, ranged from 1:28–8:10 hours) the mean hospital stay 3.6 (1–15) days.

Furthermore, Castaño-Leon et al.,¹⁶ compared endoscopic transsphenoidal surgery (ETSS) with the microscopic sublabial trans-septal transsphenoidal surgery (MTSS) for pituitary adenomas. And found that the ETSS (150 min (IQR = 60)) had none significantly shorter operative time than MTSS (180 min (IQR = 30)) (p=.054). While the ETSS (6 day (IQR = 4)) had significantly shorter hospital stay than MTSS (8 day (IQR = 4)) (p<0.001).

As well, the study by Babu et al., 10 reported that the median length of stay was 2.24 days (range 1-4 days).

Highly statistically significant (p-value < 0.001) decreased post-operative IGF-1 (242.3 ± 102.1) when compared with pre-operative IGF-1 (665 ± 253). No statistically significant difference (p-value > 0.05) between pre-operative and post-operative the following hormones (ACTH, cortisol, T3, T4, TSH, testosterone, E2, FSH, LH and PRL).

Our results were supported by Unal et al.,⁸ who reported that 29 (39.7%) of the 73 patients attained biochemical remission at the immediate postoperative period, and 16 additional patients (21.9%) were in remission based on their 3- month post-operative hormone levels. The results suggested that the mean GH IGF-1 levels were significantly improved postoperatively.

In agreement with our results the study by Aydin et al., 9 reported that The average preoperative GH level was 31.3± 21.2 ng/mL (range 2–76), while the average preoperative IGF-1 level was 657.3 ±333.7 ng/mL (range 238–1600). GH and IGF-1 levels were 1.8± 1.2 (range 0.1–10.3) ng/mL and 236.3 ±112.1 (range 84–755 ng/mL) at the final follow-up visit, respectively. At the postoperative 3rd month assessment, 63 (66.3%) patients had achieved early surgical remission.

Also, the study by Babu et al.,¹⁰ reported that at three months following surgery, 40 patients (69%) satisfied biochemical remission requirements (based GH and IGF-1 values). IGF-1 levels in eighteen of the participants remained above normal. 3 months following surgery, IGF-1 levels varied from 0.4 to 4.1 times the upper limit of normal (mean 2.6 ±0.7). The duration of long-term follow-up varied from 38 to 98 months (mean 64 months; median 28.9 months). At the 6-month follow-up, 43 (97.7%) of the 44 patients in biochemical remission stayed in remission, giving a long-term remission rate of 74.1 percent.

In addition, Taghvaei et al.,¹⁷ showed that the overall rate of remission was 71.4 percent, with gross total resection obtained in 45 out of 49 patients (91.8 percent).

CONCLUSION

In individuals with acromegaly, the endoscopic endonasal transsphenoidal technique is an efficacious and secure treatment for adenomas. We discovered that using an endoscopic endonasal transsphenoidal technique reduced growth hormone and insulin-like growth factor-1 levels considerably. To corroborate these findings, further research with a larger sample size and extended follow-up durations is required.