J Neuroendocrinol
· 2026 Jul · PMID 42396950
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Polyendocrine metabolic ovarian syndrome (PMOS) is a common endocrine disorder affecting 1.55 million women of reproductive age worldwide. While its physical and reproductive impacts are well-documented, the cognitive ef...Polyendocrine metabolic ovarian syndrome (PMOS) is a common endocrine disorder affecting 1.55 million women of reproductive age worldwide. While its physical and reproductive impacts are well-documented, the cognitive effects of PMOS remain under-researched and poorly understood. This systematic review aims to investigate existing literature on cognitive function in women with PMOS. The objective of this review is to identify specific cognitive differences between women with PMOS and those without, highlight gaps in current research and clinical care, and inform the development of more comprehensive care frameworks for individuals with PMOS. A systematic search was conducted using Ovid MEDLINE, Ovid EMBASE, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) for studies published up to June 23, 2025. Eligible studies underwent data extraction and risk of bias assessment in accordance with standard systematic review protocols. Out of 2887 articles screened, 22 studies met the inclusion criteria. Twenty-two studies involving 136,008 women with PMOS and 333,895 without PMOS were included. Across cognitive domains, pooled correlations generally indicated small, non-significant negative associations, including executive function (r = -0.12, 95% confidence interval [CI] -0.26 to 0.02), attention (r = -0.13, 95% CI -0.38 to 0.14), and working memory (r = -0.14, 95% CI -0.31 to 0.05). Substantial heterogeneity was observed in several domains, often driven by individual outlying studies. Risk of bias was generally low, and funnel plots with Egger's regression provided no evidence of publication bias. This review underscores the need for further research into the cognitive aspects of PMOS. Addressing this gap is essential for developing a more comprehensive approach to PMOS treatment and support beyond its traditional focus on physical and reproductive health.
Perets M, Carmel O, Adler A
… +4 more, Horesh N, Grozinsky-Glasberg S, Reissman P, Freund MR
J Neuroendocrinol
· 2026 Jul · PMID 42389916
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Small bowel neuroendocrine tumors (SBNET) are rare neoplasms that often present insidiously and may be associated with mesenteric fibrosis and advanced disease at diagnosis. While open surgery has traditionally been the...Small bowel neuroendocrine tumors (SBNET) are rare neoplasms that often present insidiously and may be associated with mesenteric fibrosis and advanced disease at diagnosis. While open surgery has traditionally been the standard of care, the role of laparoscopic resection in patients with complex SBNET remains under evaluation. We performed a retrospective analysis of all patients who underwent laparoscopic resection for SBNET at a tertiary referral center between 2002 and 2022. Clinical, operative, and oncologic data were extracted from a prospectively maintained database and reviewed for perioperative outcomes and long-term survival. Forty patients (mean age 62.2 years; 55% male) underwent laparoscopic resection, with a conversion rate of 7.5%. The ileum was the most common primary site (85%), and 75% of patients harbored a mesenteric mass. Postoperative morbidity was low (10%, all minor), with no perioperative mortality. The mean hospital stay was 7 days. Most tumors were low-grade (72.5% grade 1), yet 62.5% of patients presented with stage IV disease. With a mean follow-up of 7 years, overall survival reached 95 months, and progression-free survival 61 months. Age at surgery was the only independent predictor of outcome. Laparoscopic resection of SBNET is feasible and safe in selected patients, including those with advanced disease and mesenteric involvement, providing favorable long-term oncologic outcomes. These findings support the important role of minimally invasive surgery as part of the management of SBNET.
Carcinoid heart disease (CHD) is associated with advanced neuroendocrine tumor liver metastases (NETLM) and may preclude surgical cytoreduction. We assessed perioperative and long-term outcomes of hepatectomy in patients...Carcinoid heart disease (CHD) is associated with advanced neuroendocrine tumor liver metastases (NETLM) and may preclude surgical cytoreduction. We assessed perioperative and long-term outcomes of hepatectomy in patients with CHD. We retrospectively analyzed 311 patients undergoing cytoreductive hepatectomy for intestinal NETLM: non-functional (n = 163), carcinoid syndrome (CS) without CHD (n = 110), and CHD (n = 38), including patients undergoing pre-hepatectomy valve replacement. CHD patients more frequently had >10 liver metastases (78%) and larger lesions (median 9.5 cm) and required major hepatectomy more often (58%). Major morbidity was higher in CHD (up to 47%), yet 90-day mortality remained low (≤4%). Median overall survival after hepatectomy was comparable across groups (12.5 vs. 9.1 vs. 11.4 years; p = .19), including matched analyses. With optimal cardiac management, cytoreductive hepatectomy in CHD is feasible and provides long-term survival comparable to patients without CHD.
Molecular imaging of the somatostatin receptor (SSTR) plays a key role in the management of patients with neuroendocrine neoplasms in general, and neuroendocrine tumours in particular. Over the last 2 decades, gallium-68...Molecular imaging of the somatostatin receptor (SSTR) plays a key role in the management of patients with neuroendocrine neoplasms in general, and neuroendocrine tumours in particular. Over the last 2 decades, gallium-68 labelled somatostatin analogues have revolutionised SSTR imaging through the advent of SSTR positron emission tomography (PET), leading to better staging and theranostic imaging. Recent advances in the development of PET SSTR tracers continue to change the field, with novel tracers labelled with different radionuclides such as fluorine-18 and copper-64, or based on new antagonist vector molecules. The advent of these innovations generates questions, such as which tracers can be used in clinical practice, how to compare scans performed with different tracers, or can antagonists be used to select patients for peptide receptor radionuclide therapy? This 'controversy paper' from the European Neuroendocrine Tumor Society provides an overview of the relevant evidence to answer these questions, and provides guidance to clinicians and nuclear medicine physicians for contemporary use of SSTR PET.
Martín-Sánchez A, Jiménez-Díaz D, Esteve-Pérez R
… +4 more, Vasile-Tudorache A, Read JE, Howard SR, Agustín-Pavón C
J Neuroendocrinol
· 2026 Jul · PMID 42349852
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Mutations in the MECP2 gene, encoding the epigenetic reader Methyl-CpG binding protein 2, are the main cause of Rett syndrome, a rare neurodevelopmental disorder. Besides severe symptoms such as profound intellectual dis...Mutations in the MECP2 gene, encoding the epigenetic reader Methyl-CpG binding protein 2, are the main cause of Rett syndrome, a rare neurodevelopmental disorder. Besides severe symptoms such as profound intellectual disability, loss of speech and motor skills, and epilepsy, loss of function of MECP2 has been associated with pubertal dysregulation, but the biological mechanisms leading to this remain unclear. Using a mouse model of Rett, in which males are hemizygous and females heterozygous for Mecp2 loss of function mutation, we assessed the onset and progression of puberty, together with increase in body weight and onset of neurological symptoms in post-weaning mice until puberty. In brain samples of young adult mice, we analysed hypothalamic Gonadotropin releasing hormone (GnRH) neurons by immunofluorescent labelling, and in plasma samples we measured circulating GnRH, LH, and testosterone concentrations. Finally, we analysed testosterone-dependent arginine-vasopressin circuits. In our mouse model we found delayed puberty in Mecp2 -null males, associated with a reduced rate of weight gain, but with puberty onset occurring at a lower body weight than in wildtype controls. Despite later puberty onset, Mecp2-null male mice were found to have an increased number of GnRH neurons, but displayed lower levels of circulating reproductive hormones. Consequently, Mecp2-null males have deficient testosterone-dependent arginine-vasopressin innervation. In female Mecp2-heterozygous mice, we found no overall significant differences in pubertal development or GnRH neurons. The lack of significant alterations in females might be related to a later onset of neurological symptoms due to heterozygosity. Our data supports that MECP2 is essential for typical pubertal development, with complete loss of Mecp2 in a male murine model resulting in abnormalities of pubertal timing related to lower body weight, with an observed increase in hypothalamic GnRH neurons.
Augusto AGB, Dos Santos GA, Cavalheiro IVS
… +6 more, Mantovan VS, Bergantini LS, Marin NP, Dos Santos Alves E, Velloso LA, Mendes NF
J Neuroendocrinol
· 2026 Jul · PMID 42345444
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Excessive intake of saturated fats triggers inflammation in the hypothalamus, a key regulator of energy balance. In the chronic phase of this inflammatory response, bone marrow-derived and lymphoid cells are chemoattract...Excessive intake of saturated fats triggers inflammation in the hypothalamus, a key regulator of energy balance. In the chronic phase of this inflammatory response, bone marrow-derived and lymphoid cells are chemoattracted to this region, partially mitigating high-fat diet (HFD)-induced metabolic impairments. In rodents, the onset and magnitude of this inflammation differ between males and females, reflecting sex-specific patterns of metabolic regulation. However, how the hypothalamic chemokine profile evolves during HFD-induced inflammation, and whether it is influenced by biological sex, remains unclear. Here, male and female C57BL/6J mice were fed a HFD for 1, 3, 14, or 28 days. To isolate the role of ovarian hormones in modulating hypothalamic chemokine profile, we also analyzed ovariectomized (OVX) females with or without estrogen replacement. Quantitative polymerase chain reaction-based expression analysis revealed that most chemokines and their receptors were transiently modulated in the hypothalamus during the course of the HFD exposure, showing reduced levels in the acute phase and normalization during the chronic phase. Despite the modest sex-dependent effects observed, messenger RNA expression of the chemokine receptor C-X-C motif chemokine receptor 3 (CXCR3) was significantly higher in females than in males after 14 and 28 days of HFD, suggesting faster recruitment of CXCR3 immune cells that may contribute to female protection against metabolic dysfunction. Females lacking ovarian hormone production displayed increased hypothalamic expression of Cxcr3 and Ccl2. Only Cxcr3 expression was partially normalized by estradiol treatment, suggesting that non-estrogenic ovarian factors may play a role in modulating specific chemokine signaling pathways. Together, our findings show that hypothalamic chemokine signaling is dynamically and transiently regulated throughout the phases of HFD-induced inflammation, with Cxcr3 modulation by HFD and ovarian hormones contributing to sex-specific resilience against metabolic inflammation.
Bartsch DK, Mais L, de Mestier L
… +13 more, Baudin E, Kaltsas G, Hofland J, Garcia-Carbonero R, Tiensuu Janson E, McNamara MG, Andreassen M, Grozinsky-Glasberg S, Spada F, Leupe H, Panzuto F, Fleschen M, Klinkhammer H
J Neuroendocrinol
· 2026 Jul · PMID 42338092
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INTRODUCTION: VIPoma is an extremely rare functioning pancreatic neuroendocrine tumor. Therefore, data regarding treatment and outcome are very limited. Aim (s): This multicenter study aimed to analyze clinical character...INTRODUCTION: VIPoma is an extremely rare functioning pancreatic neuroendocrine tumor. Therefore, data regarding treatment and outcome are very limited. Aim (s): This multicenter study aimed to analyze clinical characteristics, real-world management, and outcomes of patients with VIPoma. METHODS: Patients with VIPoma treated in a 20-year period at 14 referral centers for neuroendocrine tumors (NET) were collected in the ENETS Database. Clinical characteristics, therapeutic interventions, and outcomes were analyzed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Of 70 patients, 59 (54% male) with a median age of 55 years were included. Forty-six (78%) patients were diagnosed due to the classical watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome, and 40 (68%) presented with distant metastases at diagnosis. Fifty-two (88%) had serum VIP levels >2 times the upper normal limit and the median Ki-67 index was 5% (range 1%-40%). Surgery of the primary VIPoma was performed in 32 (54%), with curative intent in 22 (37%). In patients with stage I-III disease (n = 19), long-term cure was achieved in only 26% (5/19), with a median DFS of 81 (95%-CI: 1-215) months and 10-year OS of 78% (95%-CI: 61%-100%). In stage IV patients (n = 53, 40 at diagnosis, 13 disease progression), the sequence and type of 354 treatment lines varied, while SSA (n = 77, 22%), loco-regional liver-directed therapy (n = 72, 20%), and chemotherapy (n = 69, 19%) were most often applied. Median OS for patients with stage IV at diagnosis was 142 (95%-CI: 87-not available (NA)) months with 10-year survival of 50% (95%-CI: 35%-73%). CONCLUSION: Patients with VIPoma treated at NET centers have relatively favorable survival, even with distant metastases at diagnosis, although long-term cure rates remain low.
J Neuroendocrinol
· 2026 Jun · PMID 42303965
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Obesity and related metabolic disorders represent major global health challenges, highlighting the importance of understanding the central regulation of energy homeostasis. The melanocortin system is a conserved circuitr...Obesity and related metabolic disorders represent major global health challenges, highlighting the importance of understanding the central regulation of energy homeostasis. The melanocortin system is a conserved circuitry governing food intake and other neuroendocrine processes. Within this system, the melanocortin-3 receptor (MC3R) regulates energy and glucose balance, body composition, and linear growth in rodent models, with evidence of sexually dimorphic expression and function. Whether MC3R exerts similar sex-specific effects in humans remains unclear, largely due to the rarity of loss-of-function (LoF) variants. We analysed data from the UK Biobank (UKB), a population-based study comprising 500,000 individuals, to investigate the phenotypic consequences of the rare MC3R LoF variant rs143321797 (p.F45S). Using the largest UKB whole-genome sequencing dataset to date, we performed comprehensive phenotypic analyses, including the first sex-stratified assessment of this variant. Carriage of the MC3R p.F45S variant was associated with differences in adult stature and the timing of sexual maturation. Though the variant was not associated with increased risk of obesity or metabolic disease, carriers exhibited an altered adipose tissue distribution profile characterised by relatively greater subcutaneous fat deposition. Our findings independently validate the role of MC3R in human stature and sexual maturation and identify a previously unreported association with adipose tissue distribution. The absence of increased obesity or metabolic disease risk in MC3R p.F45S carriers of this study, together with a subcutaneous-biased adipose distribution, suggests that MC3R may influence metabolic health through regulation of adipose tissue distribution rather than overall adiposity.
Armbruster M, Mann-Nüttel R, Mandal S
… +2 more, McVey Neufeld KA, Forsythe P
J Neuroendocrinol
· 2026 Jun · PMID 42276820
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Postpartum depression (PPD) is a mood disorder that affects the ability of mothers to engage with and care for their infants. Stress exposure is known to be a major predisposing factor for PPD, while immune factors such...Postpartum depression (PPD) is a mood disorder that affects the ability of mothers to engage with and care for their infants. Stress exposure is known to be a major predisposing factor for PPD, while immune factors such as T regulatory cells (Tregs) are also hypothesized to influence the development of the disorder. Here we assessed limited nesting (LN) in mice, with or without depletion of Tregs through anti-CD25 antibody treatment, as a potential model to investigate the relationship between stress and the immune system in PPD. Dams and their pups were exposed to LN from post-natal day 3-10 and maternal behaviour was evaluated over this period followed by assessment of maternal self-care using the splash test. Gene expression in selected brain regions and the peripheral lymphocyte profile were also assessed. LN exposure led to a significant increase in aggressive behaviour towards the pups and altered grooming in the splash test. These effects on behaviour were associated with brain region specific changes in expression of several genes related to depression and maternal behaviour and with increased levels of Tregs in the periphery. When LN was combined with anti-CD25 antibody treatment, there were further deficits in nursing behaviour and changes in the brain circuitry related to lactation and stress. Our study indicates that LN in mice may be a useful model for studying neuroimmune relationships in certain aspects of PPD. Our data also suggest that post-partum regulatory immune changes may mitigate effects of stress on brain circuitry associated with maternal behaviour, lactation and stress.
J Neuroendocrinol
· 2026 Jun · PMID 42274271
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Cushing's syndrome (CS), characterized by chronic endogenous hypercortisolism and disruption of the normal circadian cortisol rhythm, represents a unique human model for investigating the interplay between stress endocri...Cushing's syndrome (CS), characterized by chronic endogenous hypercortisolism and disruption of the normal circadian cortisol rhythm, represents a unique human model for investigating the interplay between stress endocrinology and biological aging. Glucocorticoid excess drives multiple convergent aging pathways: it suppresses telomerase activity and may accelerate telomere attrition, induces durable epigenetic remodeling, including hypomethylation of stress-responsive genes such as FKBP5, TET-mediated DNA hydroxymethylation changes, and broad dysregulation of circadian clock loci, and promotes telomere-independent senescence through mitochondrial dysfunction, oxidative stress, and cytokine-driven inflammation. These observations underpin a proposed dual-pathway model of glucocorticoid-accelerated aging, in which direct telomerase suppression and indirect epigenomic remodeling converge on common hallmarks of cellular senescence. However, clinical evidence remains heterogeneous and inconclusive: studies of leukocyte telomere length in CS report discrepant results attributable to assay platform differences, failure to correct for glucocorticoid-induced lymphopenia, small sample sizes, and predominant reliance on cross-sectional designs. Epigenetic clocks capable of quantifying biological age acceleration, particularly second-generation tools such as GrimAge and DunedinPACE, have not yet been applied to CS cohorts, representing a critical evidence gap. Furthermore, virtually all molecular aging measurements in CS have been performed in peripheral blood, leaving the causal chain from glucocorticoid excess to organ-level aging and excess mortality empirically unproven. Rather than a definitive null result, this paradox reveals that CS is an underexplored natural experiment: the syndrome's defined onset, quantifiable cortisol exposure, and surgically curable course offer a unique before-after design for testing whether stress-induced endocrine disruption genuinely accelerates biological aging through telomere and epigenetic mechanisms.
J Neuroendocrinol
· 2026 Jun · PMID 42265978
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Pregnancy and lactation trigger many metabolic adaptations, including increased food intake to support the energy demands of the growing foetus and then to provide nutrition through milk production after birth. Ghrelin,...Pregnancy and lactation trigger many metabolic adaptations, including increased food intake to support the energy demands of the growing foetus and then to provide nutrition through milk production after birth. Ghrelin, an orexigenic hormone, activates agouti related peptide (AgRP) neurons in the arcuate nucleus to promote food intake. Here, we investigated the hypothesis that increased sensitivity to ghrelin during pregnancy and lactation may contribute to elevated maternal food intake. Acute food intake was measured after a single dose of ghrelin or vehicle across reproductive states including virgin, pregnant (Day 8 and Day 15), lactating (Day 10) mice and dams 2 weeks after weaning. In vivo GCaMP fibre photometry of the AgRP neuron population was used to measure AgRP neuronal response to ghrelin. Unlike virgin mice, pregnant mice did not show an acute increase in food intake after ghrelin injection, while ghrelin-treated lactating mice showed a greater feeding response than virgin mice. After weaning, dams showed a similar increase in food intake to that seen in virgin mice. In contrast to the loss of feeding response to ghrelin, the expected increase in growth hormone (GH) in response to ghrelin was observed in both pregnancy and lactation. Across all of the reproductive states, a significant increase in AgRP neuron activity was observed in response to exogenous ghrelin administration, although the magnitude was slightly reduced in late pregnancy. Furthermore, the ghrelin-induced increase in c-Fos expression in AgRP neurons was similar in all reproductive states, indicating that AgRP neurons remained responsive to ghrelin despite the absence of a food-intake response to ghrelin during pregnancy. Interestingly, the expected drop in AgRP neuron activity in response to the presentation of food was absent during late pregnancy and lactation. The absence of a food consumption-mediated inhibition of AgRP neuron activity suggests that an attenuated response of the AgRP neurons to feedback signals associated with eating may contribute to increases in meal duration during pregnancy and lactation. Overall, these results indicate that ghrelin resistance develops during pregnancy, suggesting that ghrelin does not contribute to elevated food intake during pregnancy. In lactation, however, enhanced ghrelin sensitivity may contribute to elevated maternal food intake. These results also indicate that adaptations to ghrelin sensitivity in pregnancy and lactation are transient as 2 weeks after weaning our results are similar to the virgin state.
J Neuroendocrinol
· 2026 Jun · PMID 42259525
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Oxytocin (OT) and vasotocin (VT) are evolutionarily conserved nonapeptides that regulate a wide range of physiological and behavioral processes in vertebrates. Their receptor families have undergone gene duplications tha...Oxytocin (OT) and vasotocin (VT) are evolutionarily conserved nonapeptides that regulate a wide range of physiological and behavioral processes in vertebrates. Their receptor families have undergone gene duplications that facilitated functional diversification throughout vertebrate evolution. Using the diverse cichlid species in Lake Tanganyika, which have undergone repeated evolutionary transitions between social phenotypes, we investigated the molecular evolution of the nonapeptide system and its potential involvement in social behavior. We performed a positive selection analysis based on the dN/dS ratio and examined the correlation between amino acid variants and two social phenotypes. We also analysed gene expression data to explore associations between brain receptor expression and social phenotype variation. Our findings reveal that, while most sites in nonapeptide receptors are under strong purifying selection, a few sites- primarily in the extended intracellular loop 3 (IL3) of VTR2A receptors- show signatures of positive selection. Additionally, a specific amino acid in VTR2Aa correlates with pair-bonding, suggesting its potential role in social attachment. Gene expression analyses further revealed that components of the nonapeptide system, including VTR2Bb and OT, are differentially expressed across social phenotypes, supporting a role for regulatory variation alongside coding changes. Together, these findings provide new insights into how conserved neuroendocrine systems contribute to social diversity in cichlids.
Jacquot V, Chevalier B, Walter T
… +2 more, Gibert B, Ouzounova M
J Neuroendocrinol
· 2026 Jun · PMID 42252277
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Neuroendocrine tumours (NETs) are well-differentiated epithelial neuroendocrine neoplasms that frequently develop in the small intestine, pancreas, and lungs. NETs originate from neuroendocrine cells specialized in hormo...Neuroendocrine tumours (NETs) are well-differentiated epithelial neuroendocrine neoplasms that frequently develop in the small intestine, pancreas, and lungs. NETs originate from neuroendocrine cells specialized in hormone secretion implicated in a number of physiological processes. Their malignant transformation is characterized by low mutational burden, suggesting that epigenetic mechanisms may be at play. Recent understanding of epigenetic events driving cancer cell plasticity and tumour initiation has led to advances in the diagnosis and prognosis of NETs. Here, we provide a brief overview of NETs, including their current diagnosis and management, and present recent progress in understanding the role of epigenetic regulation, highlighting how this may influence NET tumorigenesis and may be used in therapeutic applications. Finally, this literature review emphasizes the need to gather more data on these rare malignancies to improve patient outcome.
Raycraft LM, Mo B, Doneth A
… +2 more, Lee-Tanner J, Johnson AW
J Neuroendocrinol
· 2026 Jun · PMID 42242319
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Food-related stimuli can promote feeding behaviors independent of metabolic need. Cue-potentiated feeding (CPF) studies in rodents offer the potential to reveal the psychobiological mechanisms underlying learned overeati...Food-related stimuli can promote feeding behaviors independent of metabolic need. Cue-potentiated feeding (CPF) studies in rodents offer the potential to reveal the psychobiological mechanisms underlying learned overeating behaviors. We examined whether lateral hypothalamic area (LHA) cells expressing the feeding signal Melanin Concentrating Hormone (MCH) are sufficient and necessary for CPF. Tg(Pmch-Cre) mice received bilateral infusion of the Cre-dependent inhibitory DREADD (hM4Di), or optrode placement together with the excitatory opsin ChR2. Mice received food deprivation by restricting access to two daily meal pellets. Once weight reached ~90% from baseline, Pavlovian training commenced, in which a tone or noise conditioned stimulus (CS+) predicted the delivery of a sucrose solution, whereas a second CS- was unpaired with sucrose delivery. Following a minimum of 2 days of ad-libitum pellet access, mice underwent CPF testing, where the amount of licking for sucrose in the presence of the CS+ and CS- cues was assessed. In both the chemogenetic and optogenetic studies, control mice displayed CPF as evidenced by increased lick rate during the CS+ compared to the CS-. hM4Di-mediated inhibition of LHA MCH cells significantly impaired CPF through disrupting the capacity for the CS+ to increase the mean size of licking bursts, a measure thought to index the orosensory taste properties of sucrose. By contrast, optogenetic stimulation of LHA MCH cells enhanced CPF relative to eYFP-treated controls. Our findings support a critical role for MCH-expressing neurons in the LHA in learned overeating behavior.
As peptide receptor radionuclide therapy (PRRT) maintains a key role in the treatment of neuroendocrine tumours (NETs), there is growing recognition of the importance of evaluating patient-reported health related quality...As peptide receptor radionuclide therapy (PRRT) maintains a key role in the treatment of neuroendocrine tumours (NETs), there is growing recognition of the importance of evaluating patient-reported health related quality of life (HRQoL). To assess this impact meaningfully, validated instruments such as the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaires are invaluable. This study aims to evaluate the impact of PRRT on the HRQoL of patients with NETs, using generic cancer and GI-NET-specific EORTC questionnaires to provide a comprehensive understanding of how PRRT influences patient wellbeing beyond traditional clinical endpoints. Between 2015 and 2025, patients who underwent PRRT at Royal Free London Hospital, and consented to this study, completed GI.NET21 and C30 questionnaires before PRRT is administered at each cycle. Patients who completed the pre-therapy questionnaire and at least one post-PRRT questionnaire were included in this study. The response format of both questionnaires is a 4-point Likert scale. Responses to the questionnaire were linearly transformed to a 0-100 scale using EORTC guidelines. A mean score difference >5 between any treatment cycles was considered clinically relevant, and p <.05 was considered statistically significant. GI.NET HRQoL questionnaire was completed by 267 patients, and C30 questionnaires by 147 patients. There was a statistically significant improvement between the pre-therapy score and all post PRRT treatment cycle scores in symptom scales, disease-related worries, and social function with GI.NET 21. This improvement was visible even after one PRRT cycle. A non-statistically significant improvement in overall score was seen in the pre therapy score and the third post therapy score in the C30 questionnaire. PRRT improves the quality of life and disease-specific concerns of NETs using a NET-specific HRQoL assessment tool.
The posterior hypothalamus comprises several structures involved in memory formation. Among these, neuronal populations of the lateral hypothalamus, such as melanin-concentrating hormone (MCH) neurons, and the mammillary...The posterior hypothalamus comprises several structures involved in memory formation. Among these, neuronal populations of the lateral hypothalamus, such as melanin-concentrating hormone (MCH) neurons, and the mammillary nuclei have been extensively studied. Several of these structures or populations project to the claustrum, a small subcortical region with extensive cortical connections. It has been hypothesized that the claustrum plays a pivotal role in consciousness and cognitive integration, suggesting an indirect or complementary role in mnemonic processes. However, the role of hypothalamic-claustral connections has been largely neglected. Therefore, the objective of this review is to analyze the projection patterns from specific hypothalamic tuberal neuron populations (MCH, orexin, histamine) and the supramammillary nucleus (SUM) to the claustrum, to determine whether these anatomical features can provide insights into their potential functions and stimulate further research in this domain. The SUM provides robust, specific projections to the claustrum, suggesting that these projections are part of a specialized network. Given that both the claustrum and SUM connect to the hippocampus and prefrontal cortex, it is plausible that the SUM-claustrum pathway plays a role in spatial memory encoding and representation. In contrast, the tuberal lateral hypothalamus exhibits a different projection pattern to the claustrum. MCH neurons provide significant diffuse innervation to this nucleus and surrounding cortex, while histaminergic and orexinergic projections are more scattered, targeting mostly adjacent tissues. The distribution of various receptors for these neuropeptides and neurotransmitters within the claustrum suggests functional relevance in regulating non-specific modulation of neuronal activity. These projections may be more closely related to sleep-wake regulation and, consequently, to the consolidation of episodic memory. This review highlights that hypothalamic projections to the claustrum illustrate the dual role of this small structure at the intersection of cognitive and physiological processes. The claustrum, involved in arousal and episodic memory on one hand, and spatial navigation associated with specific behavioral expression on the other, could be conceptualized as an integrative hub that coordinates cortical activity according to behavioral state (sleep/wake) through convergent cortical and subcortical inputs.