Nonfunctioning Pituitary Tumors Research Articles

Cardiovascular disease and gender differences in non-functioning pituitary tumors: preliminary data of a prospective study

Cardiovascular disease and gender differences in non-functioning pituitary tumors: preliminary data of a prospective study

TGFBR3L gene expression and relevance for the gonadotroph non-functioning pituitary neuroendocrine tumours

TGFBR3L gene expression and relevance for the gonadotroph non-functioning pituitary neuroendocrine tumours

The novel SST3 agonist ITF2984 exerts antimitotic and proapoptotic effects in human non-functioning pituitary neuroendocrine tumor (NF-PitNET) cells

The novel SST3 agonist ITF2984 exerts antimitotic and proapoptotic effects in human non-functioning pituitary neuroendocrine tumor (NF-PitNET) cells

A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification.

The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET). A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses. Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease. The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.

MiRNA Signatures Related to Invasiveness and Recurrence in Patients With Non-Functioning Pituitary Neuroendocrine Tumors.

This preliminary study aimed to analyze and identify differentially expressed miRNAs in Bulgarian patients with non-functioning pituitary neuroendocrine tumors (NFPitNET). The relationship between deregulated miRNAs and tumor invasiveness, recurrence, and size was determined. Twenty patients with NFPitNET were selected and fresh pituitary tumor tissues were collected. RNA containing miRNAs were isolated using miRNAeasy mini kit and analyzed by quantitative real-time polymerase chain reaction (PCR) using LNA miRNA Cancer-Focus PCR Panel (Qiagen). Three miRNAs (miR-210-3p, miR-149-3p, and miR-29b-3p) were deregulated in invasive compared to non-invasive NFPitNETs. Differential expression of four-miRNA signatures - miRNA-17, miR-19, miR-106a, and miR-20, correlated with patient recurrence. This prospective pilot study selected a unique miRNA expression profile, that correlates with invasiveness and recurrence in non-functioning pituitary neuroendocrine tumors. Moreover, some of the selected miRNAs are reported for the first time in patients with this disease, shedding light on the molecular mechanisms involved in pituitary pathogenesis. The identified miRNAs demonstrate potential as biomarkers, deserving further investigation in a larger cohort to validate their clinical applicability.

Mesenchymal stem cells induce an immunosuppressive microenvironment in pituitary tumors.

The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSC) and immune cells among others. MSC have been isolated from different tumors and they favor tumor cell growth, however, their role in pituitary tumors (PT) remains unknown. Herein we report the presence of MSCs in 2 ACTH-secreting PT causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF) and 2 non tumoral pituitary glands (MS). We have analyzed their transcriptomic profiles by RNAseq and compared MSC in terms of their immunosuppressive effects against lymphoid T cell and macrophage populations by means of co-cultures and flow cytometry. Our transcriptomic analysis revealed molecular differences between MSC derived from non-tumoral pituitaries and MSC derived from PT. Two distinct subpopulations of MSC, one displaying immunosuppressive properties and the other with increased pro-proliferative capabilities, regardless of their origin. MSC derived from ACTH- and nonfunctioning PT, but not those derived from non-tumoral glands significantly inhibited the proliferation of activated T cells, favored the generation of Tregs and promote M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony stimulating factor (M-CSF) and IL-10. Importantly, MSC derived from ACTH-PT showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors. This study demonstrates the presence of at least two MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSC may have important implications in PT growth.

Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

499 Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery

INTRODUCTION: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into two cohorts: 1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and 2) non-SC NFpitNETs. Rates of local tumor control, as well as the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from fourteen centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared to 8.1% of patients in the non-SC cohort (p = 0.27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, p = 0.25) or visual deficits (3.6% vs 1.1%, p = 0.088) between the two cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and gender, positive ACTH immunostaining did not have a significant correlation with local tumor progression (HR = 1.69, 95% CI = 0.8 - 3.61, p = 0.17). CONCLUSIONS: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells.

Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984's antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (-40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.

Machine Learning Analysis of Post-Operative Tumour Progression in Non-Functioning Pituitary Neuroendocrine Tumours: A Pilot Study.

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data.

Thin-slice reverse encoding distortion correction DWI facilitates visualization of non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma and surrounding normal structures

BackgroundTo evaluate the clinical usefulness of thin-slice echo-planar imaging (EPI)-based diffusion-weighted imaging (DWI) with an on-console distortion correction technique, termed reverse encoding distortion correction DWI (RDC-DWI), in patients with non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma.MethodsPatients with non-functioning PitNET/pituitary adenoma who underwent 3-T RDC-DWI between December 2021 and September 2022 were retrospectively enrolled. Image quality was compared among RDC-DWI, DWI with correction for distortion induced by B0 inhomogeneity alone (B0-corrected-DWI), and original EPI-based DWI with anterior-posterior phase-encoding direction (AP-DWI). Susceptibility artifact, anatomical visualization of cranial nerves, overall tumor visualization, and visualization of cavernous sinus invasion were assessed qualitatively. Quantitative assessment of geometric distortion was performed by evaluation of anterior and posterior displacement between each DWI and the corresponding three-dimensional T2-weighted imaging. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient values were measured.ResultsSixty-four patients (age 70.8 ± 9.9 years [mean ± standard deviation]; 33 females) with non-functioning PitNET/pituitary adenoma were evaluated. In terms of susceptibility artifacts in the frontal and temporal lobes, visualization of left trigeminal nerve, overall tumor visualization, and anterior displacement, RDC-DWI performed the best and B0-corrected-DWI performed better than AP-DWI. The right oculomotor and right trigeminal nerves were better visualized by RDC-DWI than by B0-corrected-DWI and AP-DWI. Visualization of cavernous sinus invasion and posterior displacement were better by RDC-DWI and B0-corrected-DWI than by AP-DWI. SNR and CNR were the highest for RDC-DWI.ConclusionsRDC-DWI achieved excellent image quality regarding susceptibility artifact, geometric distortion, and tumor visualization in patients with non-functioning PitNET/pituitary adenoma.Relevance statementRDC-DWI facilitates excellent visualization of the pituitary region and surrounding normal structures, and its on-console distortion correction technique is convenient. RDC-DWI can clearly depict cavernous sinus invasion of PitNET/pituitary adenoma even without contrast medium.Key points• RDC-DWI is an EPI-based DWI technique with a novel on-console distortion correction technique.• RDC-DWI corrects distortion due to B0 field inhomogeneity and eddy current.• We evaluated the usefulness of thin-slice RDC-DWI in non-functioning PitNET/pituitary adenoma.• RDC-DWI exhibited excellent visualization in the pituitary region and surrounding structures.• In addition, the on-console distortion correction of RDC-DWI is clinically convenient.Graphical

Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size

BackgroundErythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors.Methods and ResultsHuman normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size.ConclusionsOur results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis.

Different tumor growth pattern of clinically nonfunctioning pituitary neuroendocrine tumor according to sex and age: a longitudinal study.

Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66months. The median age of the patients was 53.0years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50years showed significantly lower annual tumor volume change than those aged > 50years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50years (0.01 vs. 0.15 cm3/year, P < 0.001). Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.

O-05 A novel mutation of MEN1 gene in familial Multiple Endocrine Neoplasia Type 1 (MEN1): A report of two cases

Abstract Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare (1-9/100000) autosomal dominant disease. It is characterized by primary hyperparathyroidism (90%), enteropancreatic tumor (60-70%), non-functional adrenal adenomas (30%) and pituitary tumors (10-20%). Herein, we present two cases in the same family with MEN1 syndrome caused by a novel mutation. Clinical Case 1: 49-year-old male presented to our clinic with fasting hypoglycemia. Fasting serum glucose (FSG) was 51 mg/dl and serum cortisol was 18 ug/dl. During the hypoglycemia in prolonged fasting test, the serum levels of glucose, insulin and C-peptide were 37 mg/dl, 17.3 mu/l, 7.75 ng/ml respectively (Table 1). Abdominal MRI revealed mass lesions in the pancreas (Figure 1). Ultrasonography of the neck and MIBI scintigraphy performed because of the high levels of calcium and parathyroid hormone (PTH), were consistent with parathyroid adenoma (Table 2). Pituitary MRI showed a 12 mm macroadenoma. He underwent parathyroidectomy and distal pancreatectomy simultaneously. The resected specimens revealed a well-differentiated neuroendocrine tumor (NET) of the pancreas and parathyroid adenoma. The patient had no new hypoglycemic episodes after surgery and serum calcium remained within the normal range (Table 2). Central hypothyroidism and hypogonadotropic hypogonadism which was resulted from the pressure of the adenoma was managed medically. Genetic testing revealed a heterozygous mutation in NM_001370251.1:c.949del(HET). First degree relatives of the patient were screened for MEN. Clinical Case 2: The son of case 1, an 18-year-old male, presented with fasting hypoglycemia. He had a BMI of 37 kg/m2 and underwent gastric botox 3 months prior to his presentation. FPG was 52 mg/dl and serum cortisol was 20 ug/dl. Prolonged fasting test confirmed the diagnosis of insulinoma (Table 1). Abdominal MRI showed a pancreatic tail mass 37×22 mm in size. Gallium 68 PET/CT DOTATATE revealed increased uptake in multiple lesions in the pancreas. Ultrasonography and MIBI scintigraphy showed a parathyroid adenoma. A nonfunctional microadenoma was detected in pituitary MRI. The patient underwent distal pancreatectomy. Following pancreatectomy, right superior and left inferior parathyroidectomies were performed. Since his serum calcium levels started to increase in 48 hours after the operation, the patient has had second operation for left superior parathyroidectomy. After the operation, the serum calcium and parathyroid hormone levels were 9.2 mg/dl, 58 pg/ml respectively. Specimens revealed well-differentiated NET and atypical parathyroid adenoma. The patient was found to have the same genetic mutation with his father and during the follow up the serum glucose and calcium levels remained within the normal range (Table 2). Conclusion In the genetic examination the heterozygous mutation NM_001370251.1:c.949del(HET) in exon 7/11 of the MEN1 gene found in our patients represents a novel mutation.Figure 1.MRI showing pancreatic masses Table 1.Laboratory findings Table 2.Prolonged fasting test

Differences in invasiveness and recurrence rate among nonfunctioning pituitary neuroendocrine tumors depending on tumor subtype.

To clarify the invasiveness to surrounding structures and recurrence rate of each subtype of nonfunctioning pituitary neuroendocrine tumor (Pit-NETs) according to the WHO 2022 classification. This retrospective study utilized data from 292 patients with nonfunctioning Pit-NETs treated with initial transsphenoidal surgery. Recurrence was evaluated on 113 patients who were available for a magnetic resonance imaging follow-up ≥ 60months. All tumors were assessed by immunohistochemical staining for Pit-1, T-PIT, and GATA3. Invasiveness to surrounding structures was evaluated based on intraoperative findings. Cavernous sinus invasion was found in 47.5% of null cell tumors, 50.0% of Pit-1 lineage tumors, 31.8% of corticotroph tumors, and 18.3% of gonadotroph tumors. Dura mater defects in the floor of sellar turcica, indicating dural invasion, were found in 44.3% of null cell tumors, 36.4% of corticotroph tumors, 16.7% of Pit-1 lineage tumors, and 17.3% of gonadotroph tumors. In logistic regression analysis, Pit-1 (OR 5.90, 95% CI 1.71-20.4, P = 0.0050) and null tumors (OR 4.14, 95% CI 1.86-9.23, P = 0.0005) were associated with cavernous sinus invasion. Recurrence was found in 8 (4.9%) patients, but without significant differences between tumor subtypes. The presence of cavernous sinus invasion was correlated with recurrence (HR = 1.95, 95% CI 1.10-3.46, P = 0.0227). Among nonfunctioning Pit-NETs, Pit-1 lineage tumors tend to invade the cavernous sinus, corticotroph tumors may produce dura mater defects, and null cell tumors tend to cause both. Pit-NETs with cavernous sinus invasion require a careful attention to recurrence.

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

CDC42: a potential therapeutic target of clinically non-functioning pituitary neuroendocrine tumours

CDC42: a potential therapeutic target of clinically non-functioning pituitary neuroendocrine tumours

THU089 Natural Course Of Non-Functioning Pituitary Adenoma According To Age And Sex: A Longitudinal Observational Study

Abstract Disclosure: S. Park: None. H. Kang: None. C. Ahn: None. S. Kim: None. Y. Kim: None. J. Kim: None. Backgrounds: Non-functional pituitary tumors (NFPTs) are the most common tumor among pituitary adenomas. Surgical treatment is recommended when patients present a mass effect such as a headache, visual field defect, or hormonal dysfunction. However, there is a lack of data regarding the natural course of NFPTs according to sex and age. Herein, we aimed to characterize age and sex-dependent tumor growth in patients with NFPTs. Methods: We enrolled 435 patients (males, n= 162) who were diagnosed with NFPTs and followed up at least one time and more than 12 months from 1997 to 2021 at a tertiary center. Study subjects were divided into three groups according to their age (ages≤50, 51≤age&amp;lt;65, age≥65 years). The characteristics and tumor growth of NFPTs were compared according to sex and age groups. Results: Male patients were older than female patients (median [range], 58.0 [47.0;65.0] vs. 50.0 [39.0;60.0], P&amp;lt;0.001). Annual tumor volume and percent change were higher in male patients compared to female patients (P&amp;lt;0.001, P=0.009, respectively). Despite the shorter follow-up duration in males (61 months in males vs. 71 months in females), male patients underwent surgery more often than female patients (25.9% vs. 11.4%, P&amp;lt;0.001). In male patients, there was no significant difference in the rate of tumor growth between different age groups. However, in female patients, a more rapid increase in annual tumor volume percent change was observed in the older age group compared to the younger age group (2.2 [-3.5;15.2] in females ≤50 years, 6.7 [-2.1;23.7] in 51≤ female &amp;lt;65 years, 10.1 [2.9;25.7] in female≥65 years, P=0.018). The relative risk of tumor growth of more than 20 percent, as compared with the reference group in females younger than 51 years, was 1.81 in the female group aged between 51 to 64 years (95% CI 1.06-3.08, P=0.029), and 2.45 in the female group older than 65 years (95% CI 1.16-5.18, P=0.019) compared to reference group of females younger than 51 years. Conclusion: The NFPT grows more rapidly in males than in females. The growth of NFPT was not significantly different according to age in males, however, in females, the growth of NFPT was more rapid in the older age group. Therefore, males and old females among patients with NFPTs should be more closely followed-up. Presentation: Thursday, June 15, 2023

THU069 Growth Hormone Secretion And Serum High-sensitivity C-reactive Protein Levels In Adult Patients With Non-functioning Pituitary Tumors

Abstract Disclosure: Y. Seki: None. S. Morimoto: None. K. Bokuda: None. D. Watanabe: None. S. Watanabe: None. K. Yamashita: None. N. Takano: None. A. Ichihara: None. Background: Growth hormone (GH) deficiency, which causes visceral obesity and non-alcohol fatty liver disease, increases cardiovascular event risks. Serum high-sensitivity C-reactive protein (hs-CRP) levels has been reported to estimate those risks. GH supplementation therapy was reported to decrease the serum hs-CRP levels in GH deficient patients, however, the association between GH secretion and serum hs-CRP levels have been unclear. Patients and Methods: We retrospectively reviewed charts of the patients with non-functioning pituitary adenoma and Rathke’s cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests to assess GH secretion, and investigated the association between GH secretion and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases, or received GH supplementation therapy were excluded. Results: Among 171 patients (100 NFPA and 71 Rathke’s cysts), 55 (32%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (754 [393—1330] vs 249 [113—537] ng/mL, P &amp;lt; 0.001). Serum hs-CRP levels were significantly correlated with logarithm of peak GH response to GHRP-2 (r = -0.50, P &amp;lt; 0.001), but not with IGF-1 SD score (r = -0.10, P = 0.21). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0.001) after adjustment with age, sex, BMI, smoking habit, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, abnormal liver function, and other pituitary hormone deficiencies. Severe GH deficiency were significantly associated with for serum hs-CRP levels higher than 1000 ng/mL (Odds ratio, 2.58 ;95% Confidence interval 1.15-5.78) when adjusted for obesity and abnormal liver function. Conclusion: GH secretion was significantly and negatively associated with serum hs-CRP levels independent of atherosclerotic risk factors, metabolic complications of GH deficiency, and other anterior pituitary hormone secretions. Presentation: Thursday, June 15, 2023

THU084 Corticotroph Tumor Type Influences Clinical Presentation In Patients With Nonfunctioning Pituitary Neuroendocrine Tumors

Abstract Disclosure: N. Al-Shamkhi: None. B. Edén Engström: None. O. Gudjonsson: None. J. Wikström: None. O. Casar-Borota: None. E. Rask: None. Introduction: According to the current World Health Organization classification of endocrine tumors the classification of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is based on pituitary cell lineages, defined by immunohistochemical expression of anterior pituitary hormones and pituitary specific transcription factors. The second most common NF-PitNET type, after silent gonadotroph tumors, are silent corticotroph tumors that are regarded as a potentially more aggressive type. If there is indication for treatment, the first-line treatment is transsphenoidal surgery. Some, but not all studies have shown a higher degree of preoperative pituitary failure or more frequent postoperative pituitary failure in patients with silent corticotroph tumors compared to the other NF-PitNET. Objectives: We compared patients with silent corticotroph and silent gonadotroph tumors, and explored whether tumor type and radiological findings were associated with pre- or postoperative pituitary failure. Design and method: One hundred patients who underwent surgery for NF-PitNET at the same tertiary center were included. Data regarding age at surgery, sex, pre- and postoperative pituitary function and tumor type, were collected after chart review. Preoperative MRI examinations were revised regarding tumor volume and Knosp classification. Results: The majority, 72% (72/100) were classified as silent gonadotroph tumors followed by 18% (18/100) silent corticotroph tumors. Patients with silent corticotroph tumors were younger at surgery, P=0.003. There were no differences regarding sex, preoperative tumor volume, invasive growth on MRI, defined as Knosp grade &amp;gt; 3, pituitary failure or prolactin elevation between the two tumor types. Binary logistic regression showed that having a silent corticotroph tumor, P=0.04, odds ratio 5.7 (CI: 1.06-30.71), higher age at surgery, P=0.003, odds ratio 1.07 (CI: 1.02-1.13), and a larger preoperative tumor volume, P=0.01, odds ratio 1.18 (CI: 1.04-1.33), were all factors associated with an increased likelihood of having postoperative pituitary failure. Sex, invasive growth and preoperative prolactin elevation were not significant predictors of postoperative pituitary failure in the binary logistic regression. Conclusion: The results indicate that silent corticotroph tumors influence the clinical presentation of NF-PitNET. Patients with silent corticotroph tumors were significantly younger at surgery, and demonstrated an increased likelihood of postoperative pituitary failure. Presentation: Thursday, June 15, 2023