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Pituitary Jun 2024Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of...
BACKGROUND
Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma.
METHODS
A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria.
RESULTS
A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery.
CONCLUSION
Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma.
Topics: Prolactinoma; Humans; Quality of Life; Pituitary Neoplasms; Dopamine Agonists
PubMed: 38656635
DOI: 10.1007/s11102-024-01392-1 -
Neurosurgical Review Apr 2024To analyse the imaging findings of papillary glioneuronal tumors (PGNTs), in order to improve the accuracy of preoperative diagnosis of this tumor. The clinical and...
To analyse the imaging findings of papillary glioneuronal tumors (PGNTs), in order to improve the accuracy of preoperative diagnosis of this tumor. The clinical and imaging manifestations of 36 cases of PGNT confirmed by pathology were analyzed retrospectively. A total of 17 males and 19 females, averaging 22.47 (± 11.23) years. Initial symptoms included epilepsy in ten, headache in seven, and others in 19 cases. 97.2% (35/36) of the lesions were located in the supratentorial area, and 80.5% (29/36) in the intraventricular or deep white matter adjacent to the lateral ventricles. Twenty-four of the lesions (66.7%) were mixed cystic and solid, four (11.1%) were cystic with mural nodules, four (11.1%) were cystic, and four (11.1%) were solid. Four cases of PGNT of cystic imaging showed a "T2-FLAIR mismatch" sign. 69.4% (25/36) had septations. Nine lesions (25%) were accompanied by edema, and 9 (25%) of the mixed cystic and solid lesions were accompanied by hemorrhage. Among the 18 patients who underwent computed tomography (CT) or susceptibility-weighted imaging (SWI), nine had lesions with calcification. PGNTs mostly manifest as cystic mass with mural nodules or mixed cystic and solid mass in the white matter around the supratentorial ventricle, and the cystic part of the lesion is mostly accompanied by septations. Pure cystic lesions may exhibit the sign of "T2-FLAIR mismatch". PGNT is rarely accompanied by edema but sometimes by calcification and hemorrhage. Patients often present with seizures, headaches, and mass effect symptoms.
Topics: Humans; Male; Female; Adult; Adolescent; Young Adult; Child; Magnetic Resonance Imaging; Retrospective Studies; Brain Neoplasms; Tomography, X-Ray Computed; Middle Aged; Ganglioglioma; Child, Preschool
PubMed: 38649515
DOI: 10.1007/s10143-024-02393-1 -
Frontiers in Endocrinology 2024Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine,...
Metabolic and inflammatory parameters in relation to baseline characterization and treatment outcome in patients with prolactinoma: insights from a retrospective cohort study at a single tertiary center.
BACKGROUND
Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers.
METHODS
The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage.
RESULTS
The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels.
CONCLUSION
This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.
Topics: Humans; Prolactinoma; Female; Male; Adult; Retrospective Studies; Middle Aged; Pituitary Neoplasms; Treatment Outcome; Inflammation; Tertiary Care Centers; Cabergoline; Prolactin; Prognosis; Follow-Up Studies; Cohort Studies; Young Adult
PubMed: 38645431
DOI: 10.3389/fendo.2024.1363939 -
Chinese Clinical Oncology Apr 2024The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location.
METHODS
PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old).
RESULTS
Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation.
CONCLUSIONS
Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.
Topics: Humans; Ependymoma; Radiotherapy, Adjuvant; Female; Male; Neoplasm Grading; World Health Organization
PubMed: 38644544
DOI: 10.21037/cco-23-136 -
Acta Neuropathologica Communications Apr 2024We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic...
We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.
Topics: Humans; Panobinostat; NF-E2-Related Factor 2; Neuroendocrine Tumors; Histone Deacetylase Inhibitors; Signal Transduction; Pituitary Neoplasms
PubMed: 38637883
DOI: 10.1186/s40478-024-01775-2 -
Frontiers in Endocrinology 2024Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical...
OBJECTIVE
Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure.
METHODS
Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission.
RESULTS
Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients.
CONCLUSIONS
The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.
Topics: Adult; Female; Humans; Male; Middle Aged; Acromegaly; Adenoma; Cushing Syndrome; Pituitary ACTH Hypersecretion; Pituitary Neoplasms
PubMed: 38628582
DOI: 10.3389/fendo.2024.1373869 -
BMC Endocrine Disorders Apr 2024Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study...
BACKGROUND
Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES.
METHODS
A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache.
RESULTS
In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups.
CONCLUSIONS
Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.
Topics: Humans; Pituitary Neoplasms; Retrospective Studies; Quality of Life; Treatment Outcome; Endoscopy; Headache; Sinusitis; Nasal Lavage
PubMed: 38622616
DOI: 10.1186/s12902-024-01573-w -
International Journal of Molecular... Apr 2024Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by...
Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.
Topics: Adult; Humans; Pituitary Neoplasms; Calcium; Calcium Signaling; Neoplasm Recurrence, Local; Secretagogues; Calcium, Dietary; Neoplasms, Second Primary
PubMed: 38612778
DOI: 10.3390/ijms25073968 -
International Journal of Molecular... Mar 2024Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels...
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)%, < 0.001 vs. basal, = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, < 0.001 vs. basal, = 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.
Topics: Humans; Antimitotic Agents; Neuroendocrine Tumors; Octreotide; Pituitary Neoplasms; Receptors, Somatostatin
PubMed: 38612419
DOI: 10.3390/ijms25073606 -
Frontiers in Endocrinology 2024Transsphenoidal surgery (TSS) is the preferred surgical method for most pituitary adenomas owing to high efficacy and low mortality. This study aimed to evaluate the... (Observational Study)
Observational Study
INTRODUCTION
Transsphenoidal surgery (TSS) is the preferred surgical method for most pituitary adenomas owing to high efficacy and low mortality. This study aimed to evaluate the influence of metabolic syndrome (MetS) on postoperative outcomes of TSS for pituitary adenoma.
METHODS
This population-based, retrospective observational study extracted data of adults 20-79 y receiving TSS for pituitary adenoma from the US Nationwide Inpatient Sample (NIS) between 2005-2018. Primary outcomes were pituitary-related complications, poor outcomes (i.e., in-hospital mortality or unfavorable discharge), prolonged length of stay (LOS), and patient safety indicators (PSIs). Univariate and multivariate regressions were performed to determine the associations between study variables and outcomes.
RESULTS
19,076 patients (representing a 93,185 US in-patient population) were included, among which 2,109 (11.1%) patients had MetS. After adjustment, pre-existing MetS was not significantly associated with presence of pituitary-related complications and poor outcomes. In contrast, MetS was significantly associated with an increased risk for prolonged LOS (adjusted OR (aOR) = 1.19; 95% CI: 1.05-1.34), PSIs (aOR = 1.31; 95% CI: 1.07-1.59) and greater hospital costs (adjusted β = 8.63 thousand USD; 95% CI: 4.98-12.29). Among pituitary-related complications, MetS was independently associated with increased risk of cerebrospinal fluid (CSF) rhinorrhea (aOR = 1.22, 95% CI: 1.01, 1.47) but lowered diabetes insipidus (aOR = 0.83, 95% CI: 0.71, 0.97).
DISCUSSION
MetS does not pose excessive risk of in-hospital mortality or unfavorable discharge. However, MetS independently predicted having PSIs, prolonged LOS, greater hospital costs, and CSF rhinorrhea. Study findings may help clinicians achieve better risk stratification before TSS.
Topics: Adult; Humans; Pituitary Neoplasms; Metabolic Syndrome; Inpatients; Postoperative Complications; Pituitary Diseases; Adenoma
PubMed: 38590825
DOI: 10.3389/fendo.2024.1235441