Nonfunctioning Pituitary Adenomas Research Articles

Adenomas hipofisarios no funcionantes. Incidentaloma hipofisario

Non-functioning pituitary adenomas (NFPAs) are tumors of the pituitary gland that are usually benign and show no clinical or biochemical signs of excessive hormone production. These tumors manifest clinically when they are large enough to exert pressure on surrounding structures. Among pituitary incidentaloma, NFPAs are the most common, as they are often diagnosed accidentally during imaging tests performed for other reasons. To properly evaluate these tumors and their relationship to other structures, the use of contrast-enhanced MRI is preferred. In addition, it is necessary to perform a hormonal analysis to rule out hormonal alterations and a neuro-ophthalmological examination in those cases in which the adenomas are close to the optic chiasm or cavernous sinuses, or in patients who present vision problems. In cases where the tumors are symptomless, observation is an option. However, transsphenoidal surgery is the first-line treatment for patients with symptoms or large tumors. Other options include radiation therapy and medical treatment with dopaminergic agonists and other drugs that are being explored more recently.

SZ-685C inhibits the growth of non-functioning pituitary adenoma by down-regulating miR-340-3p and inducing autophagy

BackgroundSZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. MethodsSZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. ResultsSZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 μM, and for 48 h is 4.635 ± 0.551 μM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. ConclusionsSZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

Induction of apoptosis by oridonin in nonfunctioning pituitary adenoma cells.

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay,5‑Ethynyl‑2'‑deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.

Radiological evolution of pituitary hyperplasia in primary hypothyroidism and its differentiation from nonfunctioning pituitary adenoma coexisting with primary hypothyroidism.

In a patient with elevated thyroid stimulating hormone (TSH, >50 µIU/ml) with sellar mass, it is crucial to differentiate isolated pituitary hyperplasia (IPH) from primary hypothyroidism coexisting with nonfunctioning pituitary adenoma (PHCNFPA) pre-operatively to avoid unwarranted surgery in the former condition. Here, we describe patients having pituitary mass/enlargement with markedly elevated TSH (>50 µIU/ml) and attempt to find the differentiating features between IPH and PHCNFPA. This is a retrospective study conducted at a tertiary care center. Case records of patients presenting between January 2020 and December 2022 with elevated TSH (>50 µIU/ml) for whom magnetic resonance imaging (MRI) of the sella was available were reviewed. Demographic details, symptomatology, clinical examination findings, thyroid function tests, data on pituitary hormonal excess and deficiencies, MRI findings, and details regarding levothyroxine supplementation were noted. Based on the final diagnosis, the patients were categorized into two groups: PHCNFPA and IPH. Five and 11 patients were diagnosed with PHCNFPA and IPH, respectively. The median (IQR) age at presentation of patients with PHCNFPA was significantly higher than that of IPH patients [37 (28-60.5) vs. 21 (10-21.5) years, p: 0.002]. A longer duration of hypothyroid symptoms was noted in the IPH group whereas visual field defects and corticotropin deficiency were more frequent and the pituitary lesion size was greater in PHCNFPA. Thyroid function tests were not different between the two groups. The pituitary enlargement in IPH was initially an increase in pituitary height that progressed to symmetrical nipple-, dome- or tent-shaped enlargement. Besides this characteristic enlargement pattern, isointense appearance on T1-weighted and T2-weighted images, homogeneous contrast enhancement, and prompt regression of pituitary lesion with levothyroxine replacement were characteristic of IPH whereas heterogeneous enhancement, cystic/hemorrhagic change, and ≥Knosp III invasion were characteristic of PHCNFPA. Peripheral rim enhancement and Knosp I-II parasellar extension were not uncommon in patients with IPH and did not distinguish it from PHCNFPA. The present study reports the radiological evolution of IPH and a unique series of PHCNFPA along with the distinguishing characteristics between them.

Impact of growth hormone-secreting pituitary adenoma on limbic system and its correlation with cognitive impairment

PurposeTo assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function. Method91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University −48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform. ResultsCompared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90. ConclusionPatients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment.

World premiere: transoral robot-assisted excision for nasopharyngeal ectopic pituitary adenoma.

Pituitary adenoma (PA), though rare, has seen increased incidence with widespread MRI use, enabling incidental diagnosis. Prevalence is approximately 1 case per 1000 in the general population. PAs are benign neoplasms, constituting 10 to 20% of intracranial tumours. Ectopic pituitary adenoma developed outside the sella turcica is exceptional. It may be hormonally active or not. These are called nonfunctional pituitary adenomas. Here is reported a case of a man in his eighties with a nasopharyngeal ectopic pituitary adenoma treated by robot-assisted excision using a combined route. CARE guidelines have been respected. A man in his eighties, asymptomatic, underwent an MRI for dizziness, revealing a nasopharyngeal mass. Despite being asymptomatic, nasofibroscopy revealed a reddish oval-shaped tissue mass attached to the roof of the nasopharynx. Biopsy identified a neuroendocrine tumor G1/G2. Imaging showed no local invasion or distant metastases. A multidisciplinary team decided on a robot-assisted surgical excision through the mouth, coupled with nasal endoscopy. The procedure achieved complete excision with clear margins and no adverse event has occurred. This unique case involved the successful transoral robot-assisted excision of a nasopharyngeal ectopic pituitary adenoma, highlighting an innovative surgical approach.

The diverging role of O-GlcNAc transferase in corticotroph and somatotroph adenomas.

Molecular mechanisms involved in the pathogenesis and tumor progression of pituitary adenomas (PA) remain incompletely understood. Corticotroph and somatotroph PA are associated with a high clinical burden, and despite improved surgical outcomes and medical treatment options, they sometimes require multiple surgeries and radiation. Preliminary data suggested a role for O-GlcNAc Transferase (OGT), the enzyme responsible for the O-GlcNAcylation of proteins. O-GlcNAcylation and OGT have been found elevated in other types of tumors. We evaluated 60 functioning and nonfunctioning PA (NFPA) from operated patients and postmortem normal and tumoral pituitary tissue by immunohistochemistry. We performed transcriptomic analyses to explore the relevance of the O-GlcNAc Transferase (OGT) in PAs. We detected OGT in immunobiological analysis and define its level in PA tissue in patients. OGT was strongly associated with PA hormone secretory capacity in functioning PA and with tumor growth in NFPAs. In NFPAs, OGT was positively associated with tumor size but not with cavernous sinus invasion (Knosp grading). In GH-secreting PA, OGT expression was negatively correlated with circulating Insulin-like Growth Factor 1 level. In adrenocorticotropic hormone (ACTH)-secreting PA, OGT expression was positively associated with circulating ACTH levels. OGT did not correlate with tumor size in secreting PAs. OGT levels were higher in gonadotroph PA compared to normal glands. O-GlcNAcylation can be downregulated in non-cancerous tumors such as GH-secreting adenomas. Future studies are warranted to elucidate the role of OGT in the pathogenesis of PAs.

American Association of Neurological Surgeons/Congress of the Neurological Surgeons Section on Tumors Guidelines: Assessing Their Impact on Brain Tumor Clinical Practice.

Clinical guidelines direct healthcare professionals toward evidence-based practices. Evaluating guideline impact can elucidate information penetration, relevance, effectiveness, and alignment with evolving medical knowledge and technological advancements. As the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors marks its 40th anniversary in 2024, this article reflects on the tumor guidelines established by the Section over the past decade and explores their impact on other publications, patents, and information dissemination. Six tumor guideline categories were reviewed: low-grade glioma, newly diagnosed glioblastoma, progressive glioblastoma, metastatic brain tumors, vestibular schwannoma, and pituitary adenomas. Citation data were collected from Google Scholar and PubMed. Further online statistics, such as social media reach, and features in policy, news, and patents were sourced from Altmetric. Online engagement was assessed through website and CNS+ mobile application visits. Data were normalized to time since publication. Metastatic Tumor guidelines (2019) had the highest PubMed citation rate at 26.1 per year and webpage visits (29 100 page views 1/1/2019-9/30/2023). Notably, this guideline had two endorsement publications by partner societies, the Society of Neuro-Oncology and American Society of Clinical Oncology, concerning antiepileptic prophylaxis and steroid use, and the greatest reach on X (19.7 mentions/y). Citation rates on Google Scholar were led by Vestibular Schwannoma (2018). Non-Functioning Pituitary Adenoma led Mendeley reads. News, patent, or policy publications were led by low-grade glioma at 1.5/year. Our study shows that the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors guidelines go beyond citations in peer-reviewed publications to include patents, online engagement, and information dissemination to the public.

Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

Managing nonfunctioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

Prospective, longitudinal study of cancer predictors and rates in a New York City cohort of 598 patients with acromegaly.

Long-term GH/IGF-1 excess could increase risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Therefore, we newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large NYC acromegaly cohort. We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA)(140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from SEER data. Cancer prevalence by last follow up was 22.6% in acromegaly and 12.7% in CNFPAs (OR = 1.99 (95% CI, 1.34, 2.97)(P=0.0005). Overall SIR for cancer was 1.78 (1.51, 1.81) in the acromegaly and 1.26 (0.89, 1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR=1.278 (1.060, 1.541)(P = 0.01), years from acromegaly diagnosis to cancer or last follow up, OR= 1.03 (1.004, 1.057)(P=0.024), and age at follow up, OR =1.064 (1.047, 1.082)(P<0.001), were predictors of cancer. Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

Long-term outcomes in patients with Cushing's disease vs nonfunctioning pituitary adenoma after pituitary surgery: an active-comparator cohort study.

There is increasing evidence that multisystem morbidity in patients with Cushing's disease (CD) is only partially reversible following treatment. We investigated complications from multiple organs in hospitalized patients with CD compared to patients with nonfunctioning pituitary adenoma (NFPA) after pituitary surgery. Population-based retrospective cohort study using data from the Swiss Federal Statistical Office between January 2012 and December 2021. Through 1:5 propensity score matching, we compared hospitalized patients undergoing pituitary surgery for CD or NFPA, addressing demographic differences. The primary composite endpoint included all-cause mortality, major adverse cardiac events (ie, myocardial infarction, unstable angina, heart failure, cardiac arrest, and ischemic stroke), hospitalization for psychiatric disorders, sepsis, severe thromboembolic events, and fractures in need of hospitalization. Secondary endpoints comprised individual components of the primary endpoint and surgical reintervention due to disease persistence or recurrence. After matching, 116 patients with CD (mean age 45.4 years [SD, 14.4], 75.0% female) and 396 with NFPA (47.3 years [14.3], 69.7% female) were included and followed for a median time of 50.0 months (IQR 23.5, 82.0) after pituitary surgery. Cushing's disease presence was associated with a higher incidence rate of the primary endpoint (40.6 vs 15.7 events per 1000 person-years, hazard ratio [HR] 2.75; 95% CI, 1.54-4.90). Cushing's disease patients also showed increased hospitalization rates for psychiatric disorders (HR 3.27; 95% CI, 1.59-6.71) and a trend for sepsis (HR 3.15; 95% CI, .95-10.40). Even after pituitary surgery, CD patients faced a higher hazard of complications, especially psychiatric hospitalizations and sepsis.

Differential expression of cancer-related lncRNAs in different subtypes of pituitary adenomas

Recent investigations have demonstrated abnormal expression of non-coding RNAs in pituitary adenomas. Cntribution of many lncRNAs to the pathogenesis of these tumors has not been evaluated yet. HOTTIP, ANRIL, PANDAR, PCGEM1 and HOTAIR are among lncRNAs with established roles in the pathogenesis of human cancers, particularly those originated from endocrine organs. The current study aims at assessment of expression of these lncRNAs in pituitary adenomas in comparison with the adjacent non-cancerous pituitary tissues. HOTAIR expression was absent from the majority of adenoma and non-tumoral samples. Expression of HOTTIP was significantly higher in non-functioning pituitary adenoma (NFPA) samples compared with paired normal samples (expression ratio (95 % CI)= 2.1 (1.13–2.1), P value=0.03). Expression of PANDAR was higher in total adenoma samples compared with paired normal samples (expression ratio (95 % CI)= 1.91 (1.16–3.13), P value=0.02). Expression of ANRIL was higher in NFPA samples compared with paired normal samples (expression ratio (95 % CI)= 1.94 (1.05–3.6), P value=0.048) and in total adenoma samples compared with paired normal samples (expression ratio (95 % CI)= 1.82 (1.11–2.98), P value=0.025). The current study raises the possibility of contribution of lncRNAs in the pathogenesis of at least some subtypes of pituitary adenomas and warrant further functional studies in this field.

Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology

Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

Cardiovascular risk in patients with acromegaly vs. non-functioning pituitary adenoma following pituitary surgery: an active-comparator cohort study.

Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery. This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes. Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups. This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment.

High prevalence of morphometric vertebral fractures opportunistically detected on thoracic radiograms in patients with non-functioning pituitary adenoma.

Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. We enrolled 156 patients (79M/77F, mean age 55.75 ± 12.94years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.

Postoperative Hormonal and Water Balance Disturbances After Non-Functioning Pituitary Macroadenoma Surgery

Non-functioning pituitary adenomas (NFPAs) are common sellar region tumors. Certain pituitary adenomas are categorized as functional, as they arise from specific cell types that excessively secrete hormones. In contrast, non-functional adenomas do not secrete hormones but can potentially compress the surrounding regions. The lack of hormonal activity in NFPAs often leads to a delayed diagnosis. It becomes clinically significant when the adenoma gets larger and starts causing symptoms. A 52-year-old man presented with visual field impairment since two years ago and throbbing headaches for the last three months. He was found to have pituitary macroadenoma and no hormonal excess was detected. He was diagnosed with non-functioning pituitary macroadenoma, then underwent endonasal endoscopic transsphenoidal hypophysectomy as a surgical procedure in our institute. A surgical procedure to remove pituitary adenomas can lead to high chance of complications in pituitary hormone regulation due to the manipulation of the pituitary gland and its stalk, such as water balance imbalance and hormonal disturbances. Endonasal endoscopic transsphenoidal hypophysectomy as a surgical procedure in treating pituitary macroadenoma has proven effective, resulting in good outcomes. A multidisciplinary approach involving specialists in endocrinology, ophthalmology, and neurosurgery is essential for the comprehensive evaluation of patients with pituitary adenoma.

Headache in patients with non-functioning pituitary adenoma before and after transsphenoidal surgery – a prospective study

PurposeTo study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS.MethodsWe evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS).ResultsOf 101 patients, 27 (27%) experienced disabling preoperative headache. Among these, the median total MIDAS score improved from 60 (interquartile range (IQR): 19–140) to 10 (IQR: 0–49) (P = 0.004). Additionally, headache frequency over a 90-day period decreased from 45 (IQR: 25–83) to 6 (IQR: 3–36) days (P = 0.002), and headache intensity decreased from 5 (IQR: 4–7) to 4 (IQR: 2–7) (P = 0.016) at 12-months post-surgery. At 12 months post-surgery, 18 (67%) of 27 patients with preoperatively disabling headache showed clinically relevant improvement of their headache, 4 (15%) showed deterioration, and 5 (19%) remained unchanged. In patients with clinically relevant improvement of their headache, the EQ-VAS score improved from 50 (IQR: 30 − 7) to 80 (IQR: 65–86) (P < 0.001). Of the 74 patients with no preoperative headache, 11 (15%) developed postoperative headache. We identified no clinical factors predicting postoperative headache relief.ConclusionThe study supports that clinically significant and long-lasting improvements of disabling headache and QoL can be achieved with TSS in a substantial number of patients with NFPA.

Pre-and post-surgical non-functional pituitary adenomas and their relationship with high levels of serum glucose

Objectives This clinical, analytical, retro-prospective, auto-controlled, not randomized, and not blinded study, aimed to investigate the association of changes in the serum glucose levels with the pre-and-post changes in the size tumor in mm3 in the Non-Functional pituitary adenomas. Methods Pre-and post-surgical MRI, as well as the measurements in the serum glucose levels and immunohistochemical techniques were performed in all the patients in the study, with a mean followed-up until 208.57 days. A comparison was made between the reductions in tumor size of hormonally active pituitary adenomas (HSPAs) vs NFPAs. Results Seventy-four patients were included in this study, of whom, 46 were NFPAs. The decrease in the NFPAs tumor size after surgery was statistically significant (P ≤ 0.0001). The Mean of the differences of both type of tumors in mm3 were −9552 ± 10287. Pre-surgery, the mean of the HSPAs were 8.923 ± 2.078; and the NFPAs were 14.161 ± 1.912. The differences in the tumor size were statistically significant (p = 0.039). Post-surgical, the mean of the HSPAs were 2.079 ± 971, with a (p = 0.14): and the NFPAs were 4.609 ± 1.205. After surgery of the NFPAs, most of the patients-maintained serum levels ≤ 100 mg/dL, with a statistical significance (P ≤ 0.0003). Conclusion This study demonstrates for the first time the correlation between the presence of pre-and post- surgical changes in the NFPAs, with modifications in the levels of serum glucose, and the comparison, pre- and post-surgical between the tumor size of HSPAs and NFPAs.