Central Precocious Puberty Caused by a Heterozygous Deletion in the < b > < i > MKRN3 < /i > < /b > Promoter Region
Conclusion: A rare genetic alteration in the regulatory region ofMKRN3 causes CPP. (Source: Neuroendocrinology)
Source: Neuroendocrinology - July 12, 2018 Category: Endocrinology Source Type: research

Efficacy and Safety of Sunitinib in Patients With Well-Differentiated Pancreatic Neuroendocrine Tumours
Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs,and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib. (Source: Neuroendocrinology)
Source: Neuroendocrinology - July 10, 2018 Category: Endocrinology Source Type: research

A novel synonymous variant in the AVP gene associated with adFNDI causes partial RNA missplicing
Conclusion: We have identified a synonymous variant affecting the second nucleotide of exon 3 in the AVP gene (c.324G>A) in a kindred in which adFNDI segregates. Notably, we showed that this variant causes partial missplicing of pre-mRNA resulting in accumulation of variant prohormone in ER. Our study suggests that even a small amount of aberrant mRNA might be sufficient to disturb cellular function resulting in adFNDI. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 28, 2018 Category: Endocrinology Source Type: research

18F-FDOPA PET/CT uptake parameters correlate with catecholamines secretion in human pheochromocytomas
Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. Methods: Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normeta...
Source: Neuroendocrinology - June 28, 2018 Category: Endocrinology Source Type: research

Differential Regulation of Cell Proliferation and Apoptosis by Melatonin Receptor Subtype-Signaling in the Adult Murine Brain
Conclusions: Our results indicate that generation and timing of ZT-dependent changes in cell proliferation and apoptosis by melatonin require different MT-subtype-constellations and emphasize the importance to shed light on the specific function of each receptor-subtype in different tissues and physiological conditions. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 28, 2018 Category: Endocrinology Source Type: research

Neuroanatomical Relationship of nNOS to GnRH and Kisspeptin Neurons in Adult Female Sheep and Primates
Conclusion: A lthough species differences were observed, this work establishes a neuroanatomical framework between nNOS and kisspeptin and nNOS and GnRH in adult female nonhuman primates and sheep. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 22, 2018 Category: Endocrinology Source Type: research

Stress aggravates high-fat-diet-induced insulin resistance via a mechanism that involves the amygdala and is associated with changes in neuroplasticity
Conclusions: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 20, 2018 Category: Endocrinology Source Type: research

The Lymph node ratio optimizes staging in patients with small intestinal neuroendocrine tumors
Background: The effectiveness of current Tumor, Lymph node, Metastases (TNM) staging system in small intestinal neuroendocrine tumors (SiNETs) is unsatisfactory. Current N classification only distinguishes between node-negative and node-positive status. We aim to refine the N classification for updated TNM stage. Methods: Patients with non-metastatic SiNETs between 1988 and 2012 were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database. Using the X-tile program, we calculated an optimal cut-off value for lymph node ratio (LNR) and proposed a novel Nr category. Survival outcomes were estimated using ...
Source: Neuroendocrinology - June 20, 2018 Category: Endocrinology Source Type: research

Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia
Conclusion: The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology. (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 15, 2018 Category: Endocrinology Source Type: research

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up
Conclusions: Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - June 12, 2018 Category: Endocrinology Source Type: research

The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication
Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxyt...
Source: Neuroendocrinology - June 4, 2018 Category: Endocrinology Source Type: research

Extra-Pulmonary Neuroendocrine Carcinomas: A Population-Based Study in the Netherlands
Conclusions: This study is the first nationwide study presenting an increase in the incidence of EP-NEC patients from 196 to 260 cases annually in the Netherlands. The best 5-year RS was found for EP-NEC patients with local disease located in the bladder, where the worst 5-year RS was found for patients with disease located in the oesophagus. (Source: Neuroendocrinology)
Source: Neuroendocrinology - May 31, 2018 Category: Endocrinology Source Type: research

Contents Vol. 106, 2018
Neuroendocrinology 2018;106:I –IV (Source: Neuroendocrinology)
Source: Neuroendocrinology - May 29, 2018 Category: Endocrinology Source Type: research

Central precocious puberty caused by a heterozygous deletion in the mkrn3 promoter region
Context: Loss-of-function mutations in the coding region of MKRN3, a maternally imprinted gene at chromosome 15q11.2, are a common cause of familial central precocious puberty (CPP). Whether MKRN3 alterations in regulatory regions can cause CPP has not been explored to date. We aimed to investigate potential pathogenic variants in the promoter region of MKRN3 in patients with idiopathic CPP. Patients/ Methods: A cohort of 110 patients with idiopathic CPP was studied. Family history of precocious sexual development was present in 25%. Mutations in the coding region of MKRN3 were excluded in all patients. Genomic DNA was ex...
Source: Neuroendocrinology - May 15, 2018 Category: Endocrinology Source Type: research

Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS)
Conclusions: This large international survey highlights variation in current follow-up practices not well addressed by the current guidelines. More quantitative research is required to inform the development of evidence-based guidelines tailored to the pattern of recurrence in NETs. (Source: Neuroendocrinology)
Source: Neuroendocrinology - May 2, 2018 Category: Endocrinology Source Type: research

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men
Conclusions: Our data suggest that healthy older men without late-onset hypo ­gonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH. (Source: Neuroendocrinology)
Source: Neuroendocrinology - April 24, 2018 Category: Endocrinology Source Type: research

Extra-pulmonary neuroendocrine carcinomas: A population based study in the Netherlands
Conclusions: This study is the first nationwide study presenting an increase in incidence of EP-NEC patients from 196 to 260 cases annually in the Netherlands. We found the best 5 year relative survival to be for EP-NEC patients with local disease located in the bladder, where the worst 5 year relative survival was found in the oesophagus. (Source: Neuroendocrinology)
Source: Neuroendocrinology - April 20, 2018 Category: Endocrinology Source Type: research

Interpretation of serum gonadotropin levels in hyperprolactinemia
Conclusion: The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia. (Source: Neuroendocrinology)
Source: Neuroendocrinology - April 17, 2018 Category: Endocrinology Source Type: research

The Anorexigenic Neural Pathways of Oxytocin and its Clinical Implication
Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxy...
Source: Neuroendocrinology - April 17, 2018 Category: Endocrinology Source Type: research

The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic-Pituitary-Ovarian Axis
In conclusion, our findings revealed that selective loss of neuronal AR actions impacts the kisspeptin/GnRH/LH cascade leading to compromised ovarian follicle dynamics.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - April 10, 2018 Category: Endocrinology Source Type: research

A Comprehensive Assessment of the Role of miRNAs as Biomarkers in Gastroenteropancreatic Neuroendocrine Tumors
Conclusions: A potential biomarker for GEP-NETs includedMiR-21 (small bowel and pancreas), but this epithelial tumor marker requires prospective validation. Overall, significant scientific investigation remains to identify and demonstrate neuroendocrine specificity and to validate candidate miRNA biomarkers.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 22, 2018 Category: Endocrinology Source Type: research

Presenting symptoms and delay in diagnosis of gastrointestinal and pancreatic Neuroendocrine tumours
Conclusion In conclusion, this survey demonstrates a median time to diagnosis of 36 months for patients with small bowel NETs. Incorrect initial diagnosis appears to be very common, with a high number of attendances in primary and secondary care prior to a correct diagnosis being made. An earlier diagnosis may improve patients ’ quality of life and possible survival. (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 19, 2018 Category: Endocrinology Source Type: research

Hypothalamic response to kisspeptin and pituitary response to GnRH are preserved in healthy older men
This study aimed to compare the hypothalamic response to kisspeptin and the pituitary response to GnRH of older men with those of young men. Methods: Following 1 hour of baseline sampling, healthy older men (n=5, mean age 59.3 ±2.9yrs) received a 3 hour intravenous infusion (IVI) of either: vehicle, kisspeptin-54 0.1, 0.3, 1.0nmol/kg/h, or GnRH 0.1nmol/kg/h on 5 different study days. Serum gonadotropins and total testosterone were measured every 10 minutes and compared to young men (n=5/group) (mean age 28.9±2.0yrs) wit h a similar BMI (24 kg/m2) who underwent the same protocol. Results: Kisspeptin and GnR...
Source: Neuroendocrinology - March 16, 2018 Category: Endocrinology Source Type: research

Follow-up for resected gastroenteropancreatic neuroendocrine tumours (GEP-NETs): A practice survey of the Commonwealth Neuroendocrine collaboration (CommNETs) and North American Neuroendocrine Tumor Society (NANETS)
Conclusions: This large international survey highlights variation in current foll ow-up practices not well addressed by current guidelines. More quantitative research is required to inform the development of evidence-based guidelines tailored to the pattern of recurrence in NETs. (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 15, 2018 Category: Endocrinology Source Type: research

Basic Research Advances on Pituitary Stem Cell Function and Regulation
As a central regulator of major physiological processes, the pituitary gland is a highly dynamic organ, capable of responding to hormonal demand and hypothalamic influence, through adapting secretion as well as remodelling cell numbers among its seven populations of differentiated cells. Stem cells of the pituitary have been shown to actively generate new cells during postnatal development but remain mostly quiescent during adulthood, where they persist as a long-lived population. Despite a significant body of research characterising attributes of anterior pituitary stem cells, the regulation of this population is poorly u...
Source: Neuroendocrinology - March 15, 2018 Category: Endocrinology Source Type: research

Vorspann
Neuroendocrinology 2018;106:I –XIII (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 9, 2018 Category: Endocrinology Source Type: research

Abstracts
Neuroendocrinology 2018;106:1 –301 (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 9, 2018 Category: Endocrinology Source Type: research

Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms
Conclusion: Sunitinib showed evidence of activity in patients with GEPNEN-G3 with expected toxicity profile. In the NET-G3 and NEC groups, 4/6 and 11/20 patients were responders, respectively. High p-AKT expression predicted a lower response to sunitinib. Our study allowed the identification of a potential biomarker of resistance/sensitivity to sunitinib in aggressive GEPNEN-G3.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 8, 2018 Category: Endocrinology Source Type: research

Ng2-glia, a new player in energy balance
There is increasing evidence that glia act not only as neuronal support cells, but that they can also influence physiological outcomes via effects on neural signalling. The role of NG2-glia in this regard is especially enigmatic, as they are known to interact with neural circuits but their precise functions other than as oligodendrocyte progenitor cells remain elusive. Here we summarise recent evidence suggesting that NG2-glia play a role in the maintenance of energy homeostasis, most notably via the support of leptin sensing neural circuits. We explore what this research can teach us about mechanisms of appetite control a...
Source: Neuroendocrinology - March 6, 2018 Category: Endocrinology Source Type: research

Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome
Conclusions: Sleep-related inhibition of LH pulse generation during the later follicular phase is normally weakened by brief awakenings and strengthened by REM sleep. In women with PCOS, LH pulse initiation is not appropriately discouraged by REM sleep and may be encouraged by SWS; these abnormalities may contribute to high sleep-related LH pulse frequency in PCOS. (Source: Neuroendocrinology)
Source: Neuroendocrinology - March 6, 2018 Category: Endocrinology Source Type: research

Mutual relationship between Tau and central insulin signalling: consequences for AD and Tauopathies ?
Alzheimer ’s disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in bo dy weight, brain insulin impairments and lower brain glucose metabolism, that often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone in volved in the ...
Source: Neuroendocrinology - February 14, 2018 Category: Endocrinology Source Type: research

Erratum
Neuroendocrinology 2018;106:115 –115 (Source: Neuroendocrinology)
Source: Neuroendocrinology - February 13, 2018 Category: Endocrinology Source Type: research

Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient
Treatment and prognosis of neuroendocrine neoplasia depends on tumor size, stage, grade, resectability, and extent of distant metastasis. In most cases a multimodality approach including surgical, locally invasive procedures, peptide-guided radioreceptor therapy (PRRT), and medical therapies represent the mainstay of treatment in advanced disease. In the reported case, a 68-year-old man was diagnosed in 2010 with an initially functional (histamine) neuroendocrine tumor of gastric type III, G2, stage IVB, cT4cN1cM1 (hepatic, peritoneal, nodal, osseous), including a hepatic tumor load of 25%. Intensive multimodality approach...
Source: Neuroendocrinology - January 31, 2018 Category: Endocrinology Source Type: research

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia
Conclusion: This study is the first comprehensive survival analysis of patients with SI NETs associated with mesenteric desmoplasia and has provided important and clinically relevant epidemiological data for this group of patients. (Source: Neuroendocrinology)
Source: Neuroendocrinology - January 16, 2018 Category: Endocrinology Source Type: research

Prognostic factors for survival in patients with small bowel neuroendocrine tumours associated with mesenteric desmoplasia
(Source: Neuroendocrinology)
Source: Neuroendocrinology - January 10, 2018 Category: Endocrinology Source Type: research

The Evolution of Neuroendocrine Tumor Treatment reflected by ENETS Guidelines
(Source: Neuroendocrinology)
Source: Neuroendocrinology - January 10, 2018 Category: Endocrinology Source Type: research

Extreme long survival under combined immunotherapy in a case of metastatic functional NEN-patient < br > < br >
Treatment and prognosis of neuroendocrine neoplasia (NEN) depends on tumor size, stage, grade, resectability and extent of distant metastasis.In most cases a multimodality approach incl. surgical, locally invasive procedures, peptide guided radio receptor therapy (PRRT) and medical therapies represents the mainstay of treatment in advanced disease.In the reported case, a 68-year old man was diagnosed in 2010 with an initially functional neuroendocrine tumor of gastric type III, G2, stage IVB, cT4cN1cM1 (hep., per., nod., oss.), incl. hepatic tumor load of 25%.Intensive multimodality approaches including combined immunother...
Source: Neuroendocrinology - December 20, 2017 Category: Endocrinology Source Type: research

Gut Microbiota and Host Metabolism: What Relationship?
A large number of genomic studies have reported associations between the gut microbiota composition and metabolic diseases such as obesity or type 2 diabetes. This led to the widespread idea that a causal relationship could exist between intestinal microbiota and metabolic diseases. At odds with this idea, some compelling studies reported that global changes in microbiota composition have no effect on the host metabolism in obese mice or humans. However, specific bacteria are able to confer host metabolic benefits, such asAkkermansia muciniphila orPrevotella copri, when they are given by gavage in obese mice. A crucial lin...
Source: Neuroendocrinology - November 30, 2017 Category: Endocrinology Source Type: research

GSK3 α/β: A Novel Therapeutic Target for Neuroendocrine Tumors?
Conclusion: Our data provide new insights into the role of GSK3 α/β in NETs and suggest that GSK3α/β inhibition could be a novel therapeutic option in NETs, especially in combination with lovastatin or 5-FU, depending on tumor entity.Neuroendocrinology (Source: Neuroendocrinology)
Source: Neuroendocrinology - November 16, 2017 Category: Endocrinology Source Type: research

Acknowledgement to the Reviewers
Neuroendocrinology 2017;105:435-436 (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 31, 2017 Category: Endocrinology Source Type: research

Contents Vol. 105, 2017
Neuroendocrinology 2017;105:I-IV (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 31, 2017 Category: Endocrinology Source Type: research

Subject Index Vol. 105, No. 3, 2017
Neuroendocrinology 2017;105:332 (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

Author Index Vol. 105, No. 3, 2017
Neuroendocrinology 2017;105:331 (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

Title Page / Table of Contents
Neuroendocrinology 2017;105:189-192 (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

Mechanisms of targeting the MDM2-p53-FOXM1 axis in well-differentiated intestinal neuroendocrine tumors
Conclusion: In summary, MDM2 overexpression is a frequent event in p53 wild type intestinal neuroendocrine neoplasms and therefore recovery of a p53 response might be a novel personalized treatment approach in these tumors. (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

The Genetic Basis of Delayed Puberty
The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density, and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause gonadotropin-releasing hormone (GnRH) d...
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

GSK3 α/β: A Novel Therapeutic Target for Neuroendocrine Tumors
Conclusion: Our data provide new insights into the role of GS K3α/β in NETs and suggest that GSK3α/β-inhibition could be a novel therapeutic option in NETs, especially in combination with lovastatin or 5-FU, depending on tumor entity. (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

Gut microbiota and host metabolism: what relationship
A large number of genomic studies have reported associations between the gut microbiota composition and metabolic diseases such as obesity or type 2 diabetes. This led to the widespread idea that a causal relationship could exist between intestinal microbiota and metabolic diseases. At odds with this idea, some compelling studies reported that global changes in microbiota composition have no effect on the host metabolism in obese mice or humans. However, specific bacteria are able to confer host metabolic benefits, such as Akkermansia muciniphila or Prevotella copri, when they are given by gavage in obese mice. A crucial l...
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

An evolutionary genetic perspective of eating disorders
Eating disorders (ED) including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) affect up to 5% of the population in Western countries. Risk factors for developing an ED include personality traits, family environment, gender, age, ethnicity, and culture. Despite being moderately to highly heritable with estimates ranging from 28 to 83%, no genetic risk factors have been conclusively identified. Our objective was to explore evolutionary theories of EDs to provide a new perspective on research into novel biological mechanisms and genetic causes of EDs. We developed a framework that explains the p...
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research

Abstracts of the 14th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease. March 8-10, 2017, Barcelona, Spain: Abstracts
Neuroendocrinology 2017;105(suppl 1):1-338 (Source: Neuroendocrinology)
Source: Neuroendocrinology - October 25, 2017 Category: Endocrinology Source Type: research