-
Archives of Medical Research Dec 2023Genetic testing is becoming part of mainstream endocrinology. An increasing number of rare and not-so-rare endocrine diseases have an identifiable genetic cause, either... (Review)
Review
Genetic testing is becoming part of mainstream endocrinology. An increasing number of rare and not-so-rare endocrine diseases have an identifiable genetic cause, either at the germline or at the somatic level. Here we summerise germline genetic alterations in patients with pituitary neuroendocrine tumors (pituitary adenomas). These may be disorders with isolated pituitary tumors, such as X-linked acrogigantism, or AIP-related pituitary tumors, or as part of syndromic diseases, such as multiple endocrine neoplasia type 1 or Carney complex. In some cases, this could be relevant for treatment choices and follow-up, as well as for family members, as cascade screening leads to early identification of affected relatives and improved clinical outcomes.
Topics: Humans; Pituitary Neoplasms; Adenoma; Genetic Testing; Mutation
PubMed: 38007383
DOI: 10.1016/j.arcmed.2023.102920 -
Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Annals of Surgery Apr 2023We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation.
OBJECTIVE
We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation.
SUMMARY BACKGROUND DATA
Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions.
METHODS
Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures.
RESULTS
One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53).
CONCLUSION
Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.
Topics: Humans; Bacteria; RNA, Ribosomal, 16S; Adenosine Deaminase; Gastrointestinal Microbiome; Intercellular Signaling Peptides and Proteins; Feces; Adenoma
PubMed: 35129506
DOI: 10.1097/SLA.0000000000005261 -
Gastrointestinal Endoscopy Clinics of... Apr 2022The incidence and mortality of colorectal cancer (CRC) have declined over the past several decades, largely due to improvement and uptake in screening, particularly with... (Review)
Review
The incidence and mortality of colorectal cancer (CRC) have declined over the past several decades, largely due to improvement and uptake in screening, particularly with colonoscopy. The US Multi-Society Task Force on CRC published guidelines for surveillance after polypectomy in 2012, which were updated in 2020 with some important changes, and this review will provide an updated overview of evidence and outcomes of surveillance after polypectomy. Notable modifications to surveillance guidelines include increasing interval time between colonoscopies from 5 to 7 to 10 years for 1 to 2 low-risk adenomas (<10 mm) and from 3 years to 3 to 5 years when 3 to 4 low-risk adenomas are identified.
Topics: Adenoma; Colonoscopy; Colorectal Neoplasms; Humans; Incidence; Mass Screening
PubMed: 35361341
DOI: 10.1016/j.giec.2021.12.012 -
The Journal of Clinical Endocrinology... Nov 2022Somatostatin receptor ligands (SRLs) are the cornerstone medical treatments for acromegaly; however, many patients remain unresponsive to SRLs. Well-established... (Observational Study)
Observational Study
CONTEXT
Somatostatin receptor ligands (SRLs) are the cornerstone medical treatments for acromegaly; however, many patients remain unresponsive to SRLs. Well-established predictive markers of response are needed.
OBJECTIVE
We aimed to explore the relationship between responsiveness to SRLs relative to somatostatin (SST)2A and 5 receptor expression, adenoma granularity, and T2-weighted magnetic resonance imaging (MRI) signal intensity (T2WSI).
METHODS
We conducted a multicentric, prospective, observational cohort study, in France. Forty-nine naïve patients (ie, patients without preoperative SRL treatment) with active acromegaly following surgery were treated with octreotide (group 1; n = 47), or pasireotide if uncontrolled under first-generation SRLs (group 2; n = 9). Data were collected at baseline and months 3 and 6. Biochemical measurements, immunohistochemistry studies, and MRI readings were centralized.
RESULTS
In group 1, IGF-I decrease from baseline to month 6 positively correlated with SST2A immunoreactive score (IRS), P = 0.01. Densely granulated/intermediate adenomas had a greater IGF-I and GH decrease under octreotide compared with sparsely granulated adenomas (P = 0.02 and P = 0.006, respectively), and expressed greater levels of SST2A (P < 0.001), coupled with lower levels of SST5 (P = 0.004). T2WSI changed between preoperative MRI and month 6 MRI in one-half of the patients. Finally, SST5 IRS was higher in preoperative hyperintense compared with preoperative hypointense adenomas (P = 0.04), and most sparsely granulated and most hyperintense adenomas expressed high SST5 levels.
CONCLUSION
We prospectively confirm that SST2A and adenoma granularity are good predictors of response to octreotide. We propose the IRS for scoring system harmonization. MRI sequences must be optimized to be able to use the T2WSI as a predictor of treatment response.
Topics: Humans; Acromegaly; Prospective Studies; Growth Hormone-Secreting Pituitary Adenoma; Receptors, Somatostatin; Octreotide; Insulin-Like Growth Factor I; Ligands; Adenoma
PubMed: 36136828
DOI: 10.1210/clinem/dgac512 -
La Tunisie MedicaleColonoscopy is considered as the most effective tool for preventing, screening, and diagnosing colorectal lesions. Effectiveness of colonoscopy was identified as a major... (Review)
Review
Colonoscopy is considered as the most effective tool for preventing, screening, and diagnosing colorectal lesions. Effectiveness of colonoscopy was identified as a major priority, and it strictly depends on quality measures. Therefore, international guidelines were formulated on quality indicators for colonoscopy, aiming to reduce the rate of interval cancers related to missed lesions during colonoscopy. Quality indicators are divided into 3 time periods: preprocedure, intraprocedure, and postprocedure. The main pre-procedural indicators are the assessment of the appropriateness of indication of colonoscopy and the prescription of adequate bowel preparation during a consultation prior to colonoscopy. Per-procedural criteria include all technical aspects of the procedure, which are "endoscopist-dependent" factors, particularly cecal intubation, detection of adenomas and withdrawal time. The main post-procedure indicators are the rate of complications, patient experience and optimal surveillance intervals following removal of colorectal polyps. The implementation of key performance measures in endoscopy practice is increasingly important as it can help improving our care of patients and optimize outcomes. In this review, the "Club d'endoscopie digestive" (CED) presented a summary of the main colonoscopy quality indicators, and suggested recommendations that took into account the particularities of our local conditions.
Topics: Adenoma; Cecum; Colonoscopy; Humans; Mass Screening
PubMed: 35288895
DOI: No ID Found -
Medicina Clinica Mar 2021The treatment of non-functioning pituitary adenomas raises two questions: when should they be treated and what role does each available treatment play. We review the... (Review)
Review
The treatment of non-functioning pituitary adenomas raises two questions: when should they be treated and what role does each available treatment play. We review the usefulness of the different treatments and propose a therapeutic scheme based on the existing literature. Active treatment of pituitary adenomas should be performed when they produce symptoms, have contact with the optic tract, or have grown on imaging tests. The treatment is surgical, using radiotherapy for cases with significant non-removable postsurgical tumour remnants and for those in which histopathology studies show aggressive features. Medical treatment is reserved for situations in which surgical and radiotherapy treatments have been exhausted. The most advisable surgical treatment is endoscopic, although experienced neurosurgeons achieve results with microsurgery that are only slightly inferior.
Topics: Adenoma; Endoscopy; Humans; Microsurgery; Neurosurgical Procedures; Pituitary Neoplasms; Treatment Outcome
PubMed: 33454125
DOI: 10.1016/j.medcli.2020.08.019 -
Neurosurgery Clinics of North America Oct 2019Pituitary adenomas are benign tumors, but still cause significant morbidity and in some cases increases in mortality. Surgical resection is not without risks, and... (Review)
Review
Pituitary adenomas are benign tumors, but still cause significant morbidity and in some cases increases in mortality. Surgical resection is not without risks, and approximately 40% of adenomas are incompletely resected. Medical therapies such as dopamine agonists, somatostatin analogues, and growth hormone antagonists are associated with numerous side effects. Understanding the molecular biology of pituitary adenomas may yield new therapeutic approaches. Additional studies are needed to help determine which genes or pathways are "drivers" of tumorigenesis and should be therapeutic targets. Further studies may also enable pituitary adenoma stratification to tailor treatment approaches.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Animals; DNA-Binding Proteins; Epigenesis, Genetic; Growth Hormone-Secreting Pituitary Adenoma; Humans; Pituitary Neoplasms; Prolactinoma; Signal Transduction; Viral Proteins
PubMed: 31471046
DOI: 10.1016/j.nec.2019.05.001 -
Archives of Medical Research Dec 2023Treatment strategies for NFPA include surgery, radiotherapy, medical treatment, or follow-up. The treatment of NFPAs with compressive symptoms is surgical. However, in... (Review)
Review
Treatment strategies for NFPA include surgery, radiotherapy, medical treatment, or follow-up. The treatment of NFPAs with compressive symptoms is surgical. However, in case of post-surgical tumor remnants, there may be treatment strategies that include observation and radiotherapy. Recently, medical treatment with cabergoline (CAB) has been recommended to contain and/or reduce the size of the tumor remnant. Based on the findings that many NFPAs show a dopamine receptor (DR) and somatostatin receptor (SR) expression, medical therapy with dopamine agonists (DAs) and somatostatin receptor ligands (SSRLs) has been tested as an alternative to prevent recurrence after surgery. The DAs have been the most extensively studied, showing some potential in terms of tumor shrinkage. SSRLs and other emerging medical options are much less studied. We will review and critically evaluate the current data on the medical therapy of NFPAs to elucidate their role in the management of this tumor type. In the case of actively growing remnants (more than 10% growth per year) and high-risk pituitary adenomas, treatment with CAB at a dose of 1.5-3.0 mg is indicated for tumor containment and/or reduction. In relation to combined chemotherapy with CAB, there is little information in the literature to support its use. In our experience, CAB treatment can be used after radiotherapy as an adjuvant treatment.
Topics: Humans; Pituitary Neoplasms; Receptors, Somatostatin; Adenoma; Receptors, Dopamine
PubMed: 37996269
DOI: 10.1016/j.arcmed.2023.102917 -
Frontiers in Endocrinology 2020Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas.... (Review)
Review
Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel-Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein () mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha () and G protein-coupled receptor 101 () mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene , , and mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.
Topics: Adenoma; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Genetic Predisposition to Disease; Humans; Mutation; Pituitary Neoplasms
PubMed: 33574795
DOI: 10.3389/fendo.2020.596554