Endoscopic transnasal surgery for pituitary neuroendocrine tumors (Pit-NETs) in children and young adolescents (CYP) - clinical profile, outcomes and sino-nasal quality of life - an Institutional Experience.

Objective: Although various techniques have been defined for the surgical resection of pituitary adenomas, the endoscopic transnasal transsphenoidal approach is preferred due to its wider surgical field of view and minimal invasiveness, resulting in lower complication rates. This study aimed to retrospectively analyze postoperative complications following endoscopic transnasal transsphenoidal pituitary surgery. Methods: Medical records of 2598 patients who underwent endoscopic transnasal transsphenoidal pituitary surgery between January 2018 and December 2024 were retrospectively reviewed. Data of age, gender, adenoma type, anesthesia management, and complications (and rates) were analyzed. Results: Of the patients, 53.2% (1381 patients) were female. The postoperative complication rate was 10.9% (338 patients), with the most common complications being cerebrospinal fluid (CSF) leak (4.4%), diabetes insipidus (3.3%), and epistaxis (2.6%). Apoplexy was most frequently observed in patients with non-secretory adenomas. Postoperatively, 48 patients (1.5%) required intensive care unit admission due to respiratory failure. The postoperative mortality rate was 0.4%. Conclusion: Endoscopic transnasal transsphenoidal surgery is a minimally invasive method for the treatment of pituitary adenomas. However, complications such as CSF leak, diabetes insipidus, and epistaxis may occur postoperatively. Establishing a multidisciplinary team is crucial to reduce complication risks and manage them effectively. Keywords: Transsphenoidal pituitary surgery, postoperative complications, pituitary adenomas, general anesthesia

We present an extremely rare case of lung cancer that metastasized to a gonadotroph pituitary neuroendocrine tumor, along with other organs. A 73-year-old man presented with dysarthria and bitemporal hemianopia. Head magnetic resonance imaging revealed cerebellar infarction and a pituitary tumor. Endoscopic transnasal pituitary tumor resection was performed. Pathologically, the tumor consisted of a well-differentiated neuroendocrine component, suggestive of a pituitary neuroendocrine tumor, alongside a poorly differentiated, highly malignant tumor with invasive growth. One month postoperatively, gadolinium-enhanced head magnetic resonance imaging revealed rapid growth of the residual tumor. Whole-body computed tomography and positron emission tomography revealed a 10-mm lung tumor and multiple muscle and bone metastases. Pathological examination of the pituitary tumor revealed poorly differentiated malignant cells. It was initially hypothesized that the pituitary neuroendocrine tumor had undergone malignant transformation with systemic metastases. However, further pathological examinations revealed steroidogenic factor 1-positive differentiated cells and steroidogenic factor 1-negative, synaptophysin-negative, cytokeratin-7-positive, and thyroid transcription factor-1-positive poorly differentiated malignant cells. The final diagnosis classified the tumor as a poorly differentiated lung adenocarcinoma that had metastasized to a gonadotroph pituitary neuroendocrine tumor, which showed rapid growth. Radiation and chemotherapy were administered; however, the patient died 6 months after surgery. Tumor metastasis to a pituitary neuroendocrine tumor is typically seen in older adults with non-functioning pituitary neuroendocrine tumors and no diabetes insipidus. Hence, clinicians should consider both metastatic pituitary neuroendocrine tumors and tumor metastasis to a pituitary neuroendocrine tumor when diagnosing a rapidly growing pituitary tumor in patients with signs of systemic metastasis.

We report on two cases of hepatocellular carcinoma (HCC) with metastasis to the cavernous sinus and sphenoid sinus. Both cases presented with diplopia and retro-orbital headache and both underwent surgery for a primary pituitary gland tumor. After surgery, both cases were diagnosed with metastases from HCC. Case 1 was a 67-year-old male with a history of HCC who was referred to our hospital for pituitary tumor surgery. The tumor appeared to be in the sella turcica and to invade the sphenoid sinus and right cavernous sinus. Transnasal transsphenoidal surgery (TSS) was performed. The tumor was postoperatively diagnosed by histology to be a metastatic pituitary tumor from HCC. Radiotherapy was administered to the metastatic site. Case 2 was a 58-year-old male with a history of TSS for a pituitary tumor 16years previously. He was referred to our hospital for TSS for a recurrent pituitary adenoma. TSS was performed twice in 3months. During a preoperative general examination, HCC and chronic hepatitis B were revealed. TSS was performed initially, followed by arterial infusion chemotherapy. After TSS, the pituitary tumor was diagnosed by histology to be a metastasis from HCC. As with Case 1, radiotherapy was administered to the metastasis. Most tumors in the sella turcica are pituitary adenomas, although some cases of metastatic pituitary tumors and skull base metastases have been reported. Distant metastases generally have a poor prognosis; however, surgery to the metastatic site can effectively control symptoms caused by the metastatic tumor.

Quality of life (QOL) assessment is increasingly being recognized as an important parameter while evaluating outcomes after endoscopic endonasal transsphenoidal surgery (EETS). There has been no study that has evaluated this in the Indian context. We aimed to analyze sinonasal and overall QOL before and after EETS for non-functioning pituitary adenomas (NFPAs), and to evaluate possible correlations between changes in QOL and various clinicoradiological, hormonal, and surgical factors. This prospective observational study included 62 patients who underwent EETS for NFPAs. The Anterior Skull Base Nasal Inventory-12 (ASK-12) and Short Form-12 (SF-12) were used to assess QOL. Changes in QOL were recorded at 2 weeks, 3 months, and 1-year follow-up periods. While the nasal crusting and nasal discharge components of the ASK-12 worsened 2 weeks after EETS, the headache component demonstrated significant improvement (P < 0.05). The overall ASK-12 score (6.69+/-7.98) did not change significantly at follow-up. The SF-12 physical component summary (PCS) score (42.14+/-8.54) improved progressively after surgery, while the SF-12 mental component summary (MCS) score (42.48+/-7.95) improved 1 year later. The SF-12 PCS correlated with visual field improvement at 3-month follow-up (P = 0.04). EETS affects some components of the ASK-12 without affecting the overall sinonasal QOL in patients with NFPAs. These patients demonstrate progressive postoperative improvement in physical well-being, while their mental functioning improves only a year later. Improvement in physical functioning correlates with visual field improvement at a 3-month follow-up. Hormonal dysfunction and surgical factors do not have any impact on QOL in these patients.

The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.

Given their overlapping features, pituitary metastases frequently imitate pituitary neuroendocrine tumors in neuroimaging studies. This study aimed to distinguish pituitary metastases from pituitary neuroendocrine tumors on the basis of conventional MR imaging and clinical features as a practical approach. In this 2-center retrospective study, backward from January 2024, preoperative pituitary MR imaging examinations of 22 pituitary metastases and 74 pituitary neuroendocrine tumors were analyzed. Exclusion criteria were as follows: absence of a definitive histopathologic diagnosis, history of pituitary surgery or radiation therapy before MR imaging, and pituitary neuroendocrine tumors treated with medical therapy. Two radiologists systematically evaluated 13 conventional MR imaging features that have been reported more commonly as indicative of pituitary metastases and pituitary neuroendocrine tumors in the literature. Age, sex, history of cancer, and maximum tumor size constituted the clinical/epidemiologic features. The primary cancer origin for this study was also noted. Univariable and multivariable logistic regression was used for the selection of variables, determining independent predictors, and modeling. Interobserver agreement was evaluated for all imaging parameters using the Cohen κ statistic or intraclass correlation coefficient. A total of 22 patients with pituitary metastases (8 women; mean age, 49.5 [SD, 13] years) and 74 patients with pituitary neuroendocrine tumors (36 women; mean age, 50.1 [SD, 11] years) were enrolled. There was no statistically significant distributional difference in age, sex, or maximum tumor size between the 2 groups. Lung cancer (9/22; 41%) was the most commonly reported primary tumor, followed by breast (3/22; 13.6%) and unknown cancer (3/22; 13.6%). Logistic regression revealed 3 independent predictors: rapid growth on control MR imaging, masslike or nodular expansion of the pituitary stalk, and a history of cancer. The model based on these 3 features achieved an area under the curve, accuracy, sensitivity, specificity, and Brier score of 0.987 (95% CI, 0.964-1), 97.9% (95% CI, 92.7%-99.8%), 95.5% (95% CI, 77.2%-99.9%), 98.6% (95% CI, 92.7%-100%), and 0.025, respectively. Two conventional features based on pituitary MR imaging with the clinical variable of history of cancer had satisfying predictive performance, making them potential discriminators between pituitary metastases and pituitary neuroendocrine tumors. In cases in which differentiation between pituitary metastases and pituitary neuroendocrine tumors poses a challenge, the results of this study may help with the diagnosis.

GH-secreting pituitary adenomas are nearly always visible on conventional magnetic resonance (MR) imaging. However, management and outcome of acromegalic patients lacking imaging evidence of GH-secreting pituitary adenomas are undefined. The aim was to evaluate surgical exploration for MR-invisible GH-secreting pituitary adenomas. We conducted a retrospective review at two tertiary care centers. Consecutive acromegalic patients without imaging evidence of a pituitary adenoma on pre- and postcontrast, spin echo T1-weighted MR imaging and who lacked evidence of an ectopic (nonpituitary) source causing GH excess were included. Surgical exploration with identification and resection of a pituitary adenoma was performed. Laboratory values (GH, IGF-I), surgical findings, and clinical outcome were analyzed. Six patients (three males, three females; 3% of all patients) with suspected GH-secreting adenomas did not demonstrate imaging evidence of pituitary adenoma on conventional MR imaging. Three patients underwent a postcontrast, volumetric interpolated breath-hold examination MR-imaging sequence (1.2-mm slice thickness), which revealed a 4-mm pituitary adenoma not seen on the spin echo T1-weighted MR imaging in one patient. A pituitary adenoma was identified and removed in all patients (mean diameter, 5.6 mm; range, 5 to 6.7 mm). Histological analysis confirmed that the lesions were GH-secreting adenomas. All patients achieved biochemical remission after surgical resection. Acromegaly can be caused by GH-secreting pituitary adenomas that are not evident on conventional MR imaging. Adenomas in some of these patients become evident using volumetric interpolated breath-hold examination MR imaging. Surgical exploration of the pituitary gland in acromegalic patients with endocrine findings consistent with a GH-secreting adenoma but negative MR imaging can lead to identification and removal of an adenoma.

PurposeThe expression pattern of the opioid receptor (MOR) in pituitary neuroendocrine tumors (PitNET) and the possible effect of morphine and naloxone on GH3 cell growth and apoptosis were evaluated. MethodsThe 114 pituitary tissues including non-functioning, GH-producing and ACTH-producing PitNET and healthy cadaver pituitary tissues were included. The expression level of the MOR gene and protein was assessed using real-time PCR and Western blot. The association with patient demographic characteristics was assessed. Morphine and naloxone were applied to assess their possible pharmacological role in GH3 pituitary adenoma cell death. The cytotoxic effect, the apoptosis rate, the cell cycle distribution, the content of reactive oxygen species and the caspase 3 activity were measured. ResultsMOR gene levels increased significantly in pituitary neuroendocrine tumors (PitNET) compared to the healthy pituitary samples. The increased level of MOR gene expression was prominent in invasive functional and non-functional pituitary tumors. A consistent expression pattern was demonstrated for MOR protein levels in PitNET samples. A dose- and time-dependent reduction in the rate of GH3 pituitary cells was observed after morphine treatment with an IC50 of 483 µM after 24 h of incubation. Morphine induced early apoptosis, accumulation of cells in sub-G1 phase, increase in cellular ROS levels and caspase-3 activity. The observed effects of morphine were reversed after MOR blockade using 10 and 25 µM naloxone. ConclusionThe possible contributing role of the MOR in pituitary tumor cell growth and the putative pharmaceutical effect of morphine in pituitary neuroendocrine tumor cell death (PitNET) is illustrated

Endoscopic trans-nasal trans-sphenoidal hypophysectomy is a minimally invasive surgical procedure aimed at resection of pituitary tumors. This technique is widely practiced in developed countries but is presently gaining popularity in our environment. This study was aimed at presenting our preliminary outcomes as it relates to the technique of endoscopic trans-nasal trans-sphenoidal pituitary surgery in Kano, Nigeria. This was a retrospective study of patients with pituitary tumors that presented at a government tertiary and private specialist health institutions from October 2018 to December 2019. They all had excision of varying degrees of pituitary tumors via endoscopic trans-nasal trans-sphenoidal approach under general anesthesia. There were 4 females (66.7%) and 2 males (33.3%) and their ages ranged between 25 – 60 years. They presented with varying degrees of clinical symptoms such as gynaecomastia, galactorrhea, irregular menstruation, infertility, intermittent headache and visual impairment. Four (66.7%) had complete tumor excision and 2 (33.3%) had incomplete excision. Four (66.7%) had complete symptom relief and 2 (33.3%) had significant improvement in symptoms. The complications of surgery were nasal septal adhesion 1(16.7%), CSF leak 1(16.7%) and transient diabetes insipidus 2(33.3%). All complications were resolved during admission and at follow up visits. Histopathological analysis of specimens confirmed 5 cases of pituitary adenoma and a case of pituitary Rathkes cleft cyst. Endoscopic trans-nasal trans-sphenoidal pituitary surgery is feasible and has a favorable outcome in our setting with prospects for improvement to ensure safety. Keywords: Nasal endoscopy, Sinus surgery, Pituitary tumors, Skull base, Hypophysectomy.

Endoscopic transsphenoidal surgery is currently the optimal treatment for skull base tumors. This study was designed to assess patient's sinonasal symptoms and quality of life (QoL) after resection of pituitary adenoma or skull base tumors using vascularized septal flap (VSF) reconstruction. Patients with pituitary adenoma underwent the transnasal transsphenoidal endoscopic approach (TTEA; n = 38), and patients with other benign parasellar tumors underwent the expanded endonasal approach (EEA; n = 17) with VSF. Assessment of sinonasal symptoms and QoL by the 36-item Short-Form (SF-36) and the 31-item Rhinosinusitis Outcome Measure (RSOM-31) were performed before and 3 months after surgery. At baseline, the total seven-sinonasal symptom score (T7SSS) was similar between both groups. After surgery, T7SSS significantly increased in EEA but not in TTEA patients. EEA patients reported more smell loss (40.1 ± 26.2; p < 0.05) and posterior nasal discharge (49.3 ± 30.1; p < 0.05) than TTEA patients (21.6 ± 30.9 and 22.5 ± 27.5, respectively). At baseline, both groups had poorer SF-36 compared with the general population. TTEA patients had poorer QoL (on general health, vitality, and mental health) than EEA patients. After surgery, TTEA patients showed impaired physical role and bodily pain compared with baseline, and EEA patients showed impaired physical role and mental health. At baseline, RSOM scores were similar in TTEA and EEA groups. After surgery, EEA but not TTEA patients reported poorer nasal and general symptoms. The EEA with VSF produces more sinonasal symptoms than pituitary surgery, surgery for skull base and pituitary tumors has negative impact on QoL, and functioning tumors have no further negative effect on sinonasal symptoms and QoL.

Co-existence of pituicytoma and corticotroph adenoma in a patient with Cushing's disease

Early postoperative hyponatremia (EPH, days 1–3) following pituitary neuroendocrine tumor (PitNET) surgery is a clinically significant complication with poorly defined risk factors. This study was designed to: (1) identify independent risk factors for EPH across all PitNET subtypes; (2) construct and validate a reliable predictive model using clinicopathological variables; and (3) develop a simplified risk scoring system to guide risk-stratified perioperative management. This retrospective cohort study analyzed data from 300 adult patients who underwent PitNET surgery (January 2021 – December 2024) at Nanfang Hospital. Demographics, tumor characteristics (size, Knosp grade, functional type), preoperative conditions, and surgical details were collected. EPH was defined as serum sodium < 135 mmol/L within 1–3 days postoperatively. Multivariate binary logistic regression with stepwise selection (entry criterion P < 0.10, removal criterion P > 0.10) was used to identify independent risk factors and construct the predictive model. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC), calibration plot, Hosmer-Lemeshow test, and bootstrap resampling (1000 iterations) for internal validation. The optimal risk score cutoff was determined by the Youden index. This study followed the STROBE guidelines. EPH occurred in 70 patients (23.3%). Five independent risk factors were identified: tumor diameter > 25 mm (OR = 2.85, 95% CI: 1.52–5.34, P = 0.001), Knosp grade ≥ 3 (OR = 3.10, 95% CI: 1.65–5.83, P < 0.001), adrenocorticotropic hormone (ACTH)-secreting tumor (OR = 3.55, 95% CI: 1.41–8.94, P = 0.007), preoperative hyponatremia (OR = 4.20, 95% CI: 1.81–9.74, P < 0.001), and operative duration > 180 min (OR = 2.15, 95% CI: 1.13–4.08, P = 0.019). The predictive model exhibited excellent discriminative ability (AUC = 0.85, 95% CI: 0.75–0.87) and adequate calibration (Hosmer-Lemeshow test: χ²=8.56, df = 8, P = 0.38), with robust performance confirmed by bootstrap validation (AUC = 0.83). A simplified risk scoring system (0–6 points) stratified patients into low- (0–1 points, EPH incidence 5.0%), medium- (2–3 points, 35.0%), and high-risk (≥ 4 points, 82.5%) groups. The optimal cutoff value (3 points) yielded a sensitivity of 78.6% and specificity of 83.9%. Tumor size (> 25 mm), invasiveness (Knosp grade ≥ 3), ACTH-secreting subtype, preoperative hyponatremia, and prolonged operative duration (> 180 min) are independent predictors of EPH. To our knowledge, this is the first comprehensive predictive model and simplified scoring system for EPH across all PitNET subtypes. The validated tool enables accurate preoperative risk stratification, facilitating personalized perioperative monitoring and targeted interventions to reduce EPH-related complications and improve patient outcomes.

BackgroundGrowth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels.Case presentationWe report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved.ConclusionsGH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

Somatic genetic alterations in pituitary neuroendocrine tumors (PitNET) tissues have been identified in several studies, but detection of overlapping somatic PitNET candidate genes is rare. We sequenced and by employing multiple data analysis methods studied the exomes of 15 PitNET patients to improve discovery of novel factors involved in PitNET development. PitNET patients were recruited to the study before PitNET removal surgery. For each patient, two samples for DNA extraction were acquired: venous blood and PitNET tissue. Exome sequencing was performed using Illumina NexSeq 500 sequencer and data analyzed using two separate workflows and variant calling algorithms: GATK and Strelka2. A combination of two data analysis pipelines discovered 144 PitNET specific somatic variants (mean = 9.6, range 0–19 per PitNET) of which all were SNVs. Also, we detected previously known GNAS PitNET mutation and identified somatic variants in 11 genes, which have contained somatic variants in previous WES and WGS studies of PitNETs. Noteworthy, this is the third study detecting somatic variants in gene RYR1 in the exomes of PitNETs. In conclusion, we have identified two novel PitNET candidate genes (AC002519.6 and AHNAK) with recurrent somatic variants in our PitNET cohort and found 13 genes overlapping from previous PitNET studies that contain somatic variants. Our study demonstrated that the use of multiple sequencing data analysis pipelines can provide more accurate identification of somatic variants in PitNETs.

The sphenoid sinus ostium represents the main anatomical landmark for endoscopic endonasal approaches to the sellar region, which serves as a safe entry corridor into the sphenoid sinus. Characterization of this sinus anatomy is essential for preoperative planning in pituitary neuroendocrine tumor surgery. This study aimed to analyze the morphometric features of the sphenoid sinus ostium to optimize surgical preparation.A retrospective study was conducted on computed tomography scans of 30 control individuals bilaterally (60 sides) and 30 pituitary neuroendocrine tumor patients bilaterally (60 sides). Measurements included distances from the sphenoid sinus ostium to the anterior nasal spine, sphenoid sinus floor, sphenoid sinus ceiling, and anterior sellar wall. Angles between the nasal spine and the ostium to the sellar tuberculum and sellar floor were measured.In the control group, the mean sellar and tubercular angles were 155.5° (SD ± 12.29) and 168.5° (SD ± 9.64) respectively. Longer distances to the sphenoid sinus ceiling correlated with reduced tubercular angles and increased sellar angles, while greater anterior sellar wall distance correlated with larger sellar angles. Pituitary neuroendocrine tumor group displayed a sellar angle of 132.0° (SD ± 15.49) and tubercular angle of 158.7° (SD ± 13.20), both statistically reduced compared to the control group.Sellar and tubercular angles may predict surgical endoscopic trajectory. When these angles are reduced, extensive removal of the posterior ethmoid cells and sphenoid rostrum may be required to adequately expose the tubercular recess and sellar floor, respectively. Preoperative analysis of sphenoid sinus ostium morphometry for surgical planning may guide the extent of bone removal needed, enhancing safety in pituitary neuroendocrine tumor surgery.