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Frontiers in Endocrinology 2023The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central... (Review)
Review
The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central nervous system through the microbiome-brain-gut axis in the past ten years. As more and more research has been done on the relationship between the disease of the central nervous system and gut microbes. This fact is being revealed that gut microbes seem to play an important role from the onset and progression of the disease to clinical symptoms, and new treatments. As a special tumor of the central nervous system, pituitary neuroendocrine tumors (PitNETs)are closely related to metabolism, endocrinology, and immunity. These factors are the vectors through which intestinal microbes interact with the central nervous system. However, little is known about the effects of gut microbes on the PitNET. In this review, the relationship of gut microbiota in PitNETs is introduced, the potential effects of the gut-brain axis in this relationship are analyzed, and future research directions are presented.
Topics: Humans; Gastrointestinal Microbiome; Brain; Central Nervous System; Pituitary Neoplasms; Neuroendocrine Tumors
PubMed: 38027221
DOI: 10.3389/fendo.2023.1255911 -
Endocrine Nov 2023Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is...
PURPOSE
Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan.
METHODS
We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected.
RESULTS
Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria.
CONCLUSIONS
The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported.
Topics: Humans; Tolvaptan; Inappropriate ADH Syndrome; Antidiuretic Hormone Receptor Antagonists; Retrospective Studies; Benzazepines; Hyponatremia; Sodium
PubMed: 37507553
DOI: 10.1007/s12020-023-03457-w -
World Journal of Gastroenterology Sep 2023Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder,... (Review)
Review
BACKGROUND
Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder, usually results from a growth hormone (GH)-secreting pituitary adenoma.
CASE SUMMARY
We herein describe a 38-year-old patient who was initially diagnosed with diabetes. During colonoscopy, two bulges were identified and subsequently removed through endoscopic submucosal dissection. Following the surgical intervention, the excised tissue samples were examined and confirmed to be grade 2 NET. F-ALF-NOTATATE positron emission tomography-computed tomography (PET/CT) and Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes, prompting laparoscopic low anterior resection with total mesorectal excision. The patient later returned to the hospital because of hyperglycemia and was found to have facial changes, namely a larger nose, thicker lips, and mandibular prognathism. Laboratory tests and magnetic resonance imaging (MRI) suggested a GH-secreting pituitary adenoma. The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected a trans-sphenoidal approach. Whole-exome sequencing analysis revealed no genetic abnormalities. The patient recovered well with no evidence of recurrence during follow-up.
CONCLUSION
F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.
Topics: Humans; Adult; Pituitary Neoplasms; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Adenoma; Rectal Neoplasms
PubMed: 37753367
DOI: 10.3748/wjg.v29.i34.5082 -
Endocrine Journal Oct 2023An association exists between nonalcoholic fatty liver disease (NAFLD) and growth hormone (GH). Patients with growth hormone deficiency (GHD) may be more susceptible to... (Meta-Analysis)
Meta-Analysis
An association exists between nonalcoholic fatty liver disease (NAFLD) and growth hormone (GH). Patients with growth hormone deficiency (GHD) may be more susceptible to NAFLD. The prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) in GHD patients is currently unknown. Multiple databases were searched for experiments related to NAFLD (or NASH) and GHD. Screening, quality evaluation and data extraction were carried out independently by two authors. Analyses used random or fixed effects models, including NAFLD prevalence, NASH prevalence, odds ratio (OR) and 95% confidence interval (CI). We included 10 studies with a total of 782 participants. The results showed that the prevalence of NAFLD in GHD patients was 51% (95% CI: 39-63). The risk of NAFLD in GHD patients was significantly higher than that in controls (age-, sex- or body mass index-matched, without GHD) (pooled OR = 4.27, 95% CI: 1.33-13.68%, p = 0.015). The prevalence of NASH in GHD patients was 18% (95% CI: 5-31). The prevalence of NAFLD in GHD patients is significantly higher than that in the general population, especially NASH. There is a need to develop targeted strategies for the early identification, prevention, or control of NAFLD/NASH in patients with GHD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Hypopituitarism; Risk Assessment; Growth Hormone; Liver
PubMed: 37468264
DOI: 10.1507/endocrj.EJ23-0157 -
Frontiers in Endocrinology 2023Pituitary neuroendocrine tumors (PitNETs), which originate from the pituitary gland, account for 10%-15% of all intracranial neoplasms. Recent studies have indicated...
BACKGROUND
Pituitary neuroendocrine tumors (PitNETs), which originate from the pituitary gland, account for 10%-15% of all intracranial neoplasms. Recent studies have indicated that enhancer RNAs (eRNAs) exert regulatory effects on tumor growth. However, the mechanisms underlying the eRNA-mediated tumorigenesis of PitNETs have not been elucidated.
METHODS
Normal pituitary and PitNETs tissues were used to identify the differentially expressed eRNAs (DEEs). Immune gene sets and hallmarks of cancer gene sets were quantified based on single sample gene set enrichment analysis (ssGSEA) algorithm using GSVA. The perspective of immune cells among all samples was calculated by the CIBERSORT algorithm. Moreover, the regulatory network composed of key DEEs, target genes of eRNAs, hallmarks of cancer gene sets, differentially expressed TF, immune cells and immune gene sets were constructed by Pearson correlation analysis. Small molecular anti-PitNETs drugs were explored by CMap analysis and the accuracy of the study was verified by and experiments, ATAC-seq and ChIP-seq.
RESULTS
In this study, data of 134 PitNETs and 107 non-tumorous pituitary samples were retrieved from a public database to identify differentially expressed genes. In total, 1128 differentially expressed eRNAs (DEEs) (494 upregulated eRNAs and 634 downregulated eRNAs) were identified. Next, the correlation of DEEs with cancer-related and immune-related gene signatures was examined to establish a co-expression regulatory network comprising 18 DEEs, 50 potential target genes of DEEs, 5 cancer hallmark gene sets, 2 differentially expressed transcription factors, 4 immune cell types, and 4 immune gene sets. Based on this network, the following four therapeutics for PitNETs were identified using Connectivity Map analysis: ciclopirox, bepridil, clomipramine, and alexidine. The growth-inhibitory effects of these therapeutics were validated using experiments. Ciclopirox exerted potential growth-inhibitory effects on PitNETs. Among the DEEs, , and were determined to be potential diagnostic and therapeutic biomarkers for PitNETs.
CONCLUSION
This study illustrated the significant influence of eRNAs on the occurrence and development of PitNETs. By constructing the co-expression regulation network, , and were identified as relatively significant DEEs which were considered as the novel biomarkers of diagnosis and treatment of PitNETs. This study demonstrated the roles of eRNAs in the occurrence and development of PitNETs and revealed that ciclopirox was a potential therapeutic for pituitary adenomas.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Ciclopirox; RNA; Transcription Factors; Pituitary Gland; Homeodomain Proteins
PubMed: 37534217
DOI: 10.3389/fendo.2023.1149997 -
Japanese Journal of Radiology Aug 2023Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO... (Review)
Review
Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO Classification of Central Nervous System Tumors and the 2022 WHO Classification of Endocrine and Neuroendocrine Tumors), various changes have been made to the tumors other than pituitary neuroendocrine tumor (PitNET)/pituitary adenoma, as well as PitNET. Adamantinomatous craniopharyngioma and papillary craniopharyngioma are now considered separate tumors in the 5th edition of the WHO classification. Tumors positive for thyroid transcription factor 1, a marker of posterior pituitary cells, are now grouped together in the pituicyte tumor family in the 5th edition of the WHO classification of Endocrine and Neuroendocrine Tumors. Poorly differentiated chordoma is newly listed in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. In this paper, we present the latest WHO classification of pituitary tumors (adamantinomatous craniopharyngioma, papillary craniopharyngioma, pituitary blastoma, pituicyte tumor family, tumors of pituitary origin other than those of the pituicyte tumor family, germinoma, meningioma, chordoma, metastatic tumors, lymphoma, and pituitary incidentaloma), review diseases requiring differentiation from tumors (pituitary abscess, hypophysitis, pituitary hyperplasia, Rathke's cleft cyst, arachnoid cyst, and aneurysm), and discuss diagnoses based on imaging findings.
Topics: Humans; Pituitary Neoplasms; Craniopharyngioma; Chordoma; Pituitary Gland; Pituitary Diseases; Adenoma; Neuroendocrine Tumors; Meningeal Neoplasms; World Health Organization
PubMed: 36913010
DOI: 10.1007/s11604-023-01407-0 -
Endocrine Jul 2023To retrospectively summarize the clinical features of acromegaly complicated with fulminant pituitary apoplexy and analyze the prognostic factors to guide early... (Review)
Review
PURPOSE
To retrospectively summarize the clinical features of acromegaly complicated with fulminant pituitary apoplexy and analyze the prognostic factors to guide early identification and timely treatment of such patients.
METHODS
A retrospective analysis was carried out to summarize the clinical manifestations, hormone changes, imaging, treatment and follow-up of ten patients with acromegaly complicated with fulminant pituitary apoplexy admitted to our hospital from February 2013 to September 2021.
RESULTS
The mean age of the ten patients (five males and five females) at the time of pituitary apoplexy was 37.1 ± 13.4 years old. There were nine cases with sudden severe headaches and five cases with visual impairment. All patients had pituitary macroadenomas, of which six cases with Knosp grade ≥3. The level of GH/IGF-1 hormone after pituitary apoplexy was lower compared with pre-apoplexy, and 1 patient reached biochemical remission spontaneously. Seven patients underwent transsphenoidal pituitary surgery after apoplexy and one patient was treated with long-acting somatostatin analog. The biochemical remission rate was 37.5% in eight patients immediately after treatment and 50% at the last follow-up. Patients with Knosp grade ≥3 were less likely to achieve biochemical remission than those with Knosp grade <3 (16.7% vs. 100%, p = 0.048), and patients who achieved biochemical remission had a smaller maximum tumor diameter [20.1 (20.1,28.0) mm vs. 44.0 (44.0,60) mm, p = 0.016].
CONCLUSION
Acromegaly complicated with fulminant pituitary apoplexy remains a diagnostic and therapeutic challenge.
Topics: Male; Female; Humans; Young Adult; Adult; Middle Aged; Acromegaly; Adenoma; Retrospective Studies; Pituitary Apoplexy; Pituitary Neoplasms; Somatostatin; Treatment Outcome
PubMed: 37195580
DOI: 10.1007/s12020-023-03379-7 -
Pituitary Aug 2023Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical... (Review)
Review
OBJECTIVE
Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical signs, symptoms and comorbidities of acromegaly at time of diagnosis.
DESIGN
A literature search (in PubMed, Embase and Web of Science) was performed on November 18, 2021, in collaboration with a medical information specialist.
METHODS
Prevalence data on (presenting) clinical signs, symptoms and comorbidities at time of diagnosis were extracted and synthesized as weighted mean prevalence. The risk of bias was assessed for each included study using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.
RESULTS
Risk of bias and heterogeneity was high in the 124 included articles. Clinical signs and symptoms with the highest weighted mean prevalence were: acral enlargement (90%), facial features (65%), oral changes (62%), headache (59%), fatigue/tiredness (53%; including daytime sleepiness: 48%), hyperhidrosis (47%), snoring (46%), skin changes (including oily skin: 37% and thicker skin: 35%), weight gain (36%) and arthralgia (34%). Concerning comorbidities, acromegaly patients more frequently had hypertension, left ventricle hypertrophy, dia/systolic dysfunction, cardiac arrhythmias, (pre)diabetes, dyslipidemia and intestinal polyps- and malignancy than age- and sex matched controls. Noteworthy, cardiovascular comorbidity was lower in more recent studies. Features that most often led to diagnosis of acromegaly were typical physical changes (acral enlargement, facial changes and prognatism), local tumor effects (headache and visual defect), diabetes, thyroid cancer and menstrual disorders.
CONCLUSION
Acromegaly manifests itself with typical physical changes but also leads to a wide variety of common comorbidities, emphasizing that recognition of a combination of these features is key to establishing the diagnosis.
Topics: Humans; Acromegaly; Prevalence; Delayed Diagnosis; Comorbidity; Headache; Hypertension; Diabetes Mellitus
PubMed: 37210433
DOI: 10.1007/s11102-023-01322-7 -
EBioMedicine Jan 2024The long-standing view of senescent cells as passive and dysfunctional biological remnants has recently shifted into a new paradigm where they are main players in the... (Review)
Review
The long-standing view of senescent cells as passive and dysfunctional biological remnants has recently shifted into a new paradigm where they are main players in the development of many diseases, including cancer. The senescence programme represents a first line of defence that prevents tumour cell growth but also leads to the secretion of multiple pro-inflammatory and pro-tumourigenic factors that fuel tumour initiation, growth, and progression. Here, we review the main molecular features and biological functions of senescent cells in cancer, including the outcomes of inducing or targeting senescence. We discuss evidence on the role of cellular senescence in pituitary tumours, with an emphasis on adamantinomatous craniopharyngioma (ACP) and pituitary adenomas. Although senescence has been proposed to be a tumour-preventing mechanism in pituitary adenomas, research in ACP has shown that senescent cells are tumour-promoting in both murine models and human tumours. Future studies characterizing the impact of targeting senescent cells may result in novel therapies against pituitary tumours.
Topics: Humans; Mice; Child; Animals; Pituitary Neoplasms; Pituitary Gland; Craniopharyngioma; Carcinogenesis; Cell Transformation, Neoplastic; Cellular Senescence
PubMed: 38043401
DOI: 10.1016/j.ebiom.2023.104905 -
Frontiers in Endocrinology 2023Hedgehog signaling plays pivotal roles in embryonic development, adult homeostasis and tumorigenesis. However, its engagement in the pituitary gland has been long... (Review)
Review
Hedgehog signaling plays pivotal roles in embryonic development, adult homeostasis and tumorigenesis. However, its engagement in the pituitary gland has been long underestimated although Hedgehog signaling and pituitary embryogenic development are closely linked. Thus, deregulation of this signaling pathway during pituitary development results in malformation of the gland. Research of the last years further implicates a regulatory role of Hedgehog signaling in the function of the adult pituitary, because its activity is also interlinked with homeostasis, hormone production, and most likely also formation of neoplasms of the gland. The fact that this pathway can be efficiently targeted by validated therapeutic strategies makes it a promising candidate for treating pituitary diseases. We here summarize the current knowledge about the importance of Hedgehog signaling during pituitary development and review recent data that highlight the impact of Hedgehog signaling in the healthy and the diseased adult pituitary gland.
Topics: Adult; Humans; Hedgehog Proteins; Pituitary Gland; Signal Transduction; Pituitary Neoplasms; Pituitary Diseases
PubMed: 37476499
DOI: 10.3389/fendo.2023.1219018