Neuroendocrinology最新文献

This review covers current classification systems and the knowledge of genetic disorders and medical therapies. Thymic carcinoids or neuroendocrine neoplasms (t-NEN) are a rare entity with dismal prognosis. About 25% of the tumors are related to Multiple Endocrine Neoplasia type I (MEN-1), where they contribute significantly to mortality. The tumors are classified according to the WHO classification, TNM classification and Masaoka-Koga staging system, although none of the classifications have been developed for t-NEN. A recently proposed t-NEN specific morphomolecular classification is based on copy number instability scores. Its role is to be defined yet. The prognosis depends on resectability, histological features, metastasis, the amount of copy number instabilities and mitotic activity. No study based therapies exist. The mainstay of therapy is surgical resection, as it is associated with significantly improved long-term survival. Based on published cases and small series, for non-resectable and recurring disease platinum based chemotherapies are preferred in neuroendocrine carcinoma (t-NEC) while everolimus and temozolomide are recommended in thymic neuroendocrine tumors (t-NET).

Background Neuroendocrine neoplasms (NENs) are consistently referred to as a 'relatively' rare heterogenous group of 'tumours' with variability in their disease course and outcomes [1-7]. However, there is a lack of consensus in a) the group membership, that is, a lack of consistency in which 'sub-types' of NEN are included in the group, b) whether they should continue to be seen as a 'heterogenous group', or as separate entities and c) whether the term and current definitions of 'rare' accurately reflects the true patient population and healthcare requirement. Summary This opinion paper explores the concept of rare, as applied to NENs: the significance of a rare cancer label and what this means for awareness, healthcare provision and, tangentially, those diagnosed. It also asks whether the currently utilised rare cancer definitions reflect an accurate representation of the true disease burden and fully inform disease-appropriate healthcare planning and provision. Key Messages The current definition of 'rare cancer' based on incidence alone, fails to reflect the true disease burden of NENs, and is therefore inadequate, to fully inform healthcare policy, planning and provision for this patient population. This requires either a revision in definition or an alteration in how and what decision-makers utilise and include in their deliberations when assessing and planning service provision.

Introduction: Chronic cocaine exposure results in changes in circulating steroid hormones, which is known to be associated with cocaine-seeking and taking behavior. However, whether cocaine also alters the brain content of these steroid hormones and cholesterol, a precursor to all steroid hormones, has yet to be extensively investigated. Thus, the goal of this study was to determine whether cocaine self-administration (SA) altered the content of cholesterol and steroid hormones (progesterone and testosterone) in both the plasma and the brain of animals.

Methods: Male Sprague-Dawley rats were allowed to self-administer cocaine (1.5 mg/kg/infusion) for a maximum 40 injections within 6 hours per day for 5 consecutive days followed by cue reactivity test and cocaine SA under the progressive ratio schedule as a measure of motivation to acquire cocaine. Eighteen hours after the last behavior test, the blood and brain tissue, including the prefrontal cortex (PFC) and dorsal striatum (CPu), were collected for biochemical assays.

Results: While cocaine SA did not alter the content of cholesterol and progesterone in the plasma, it reduced cholesterol content and almost completely abolished progesterone content in both the PFC and CPu. Further, testosterone levels were reduced in the CPu and plasma. Notably, plasma testosterone was positively correlated with its content in the PFC and CPu.

Conclusions: Cholesterol and progesterone in the brain are more sensitive to changes induced by cocaine SA than those in the plasma. Future studies should focus on understanding the functional consequence of altered brain steroids on neurotransmission and cocaine-seeking and taking behavior.

Introduction: Pelvic ultrasound has been studied for the follow-up of girls with precocious puberty during gonadotropin-releasing hormone agonists (GnRHa) therapy. The addition of Doppler evaluation of uterine arteries needs to be further investigated. We aimed to evaluate the accuracy of the uterine artery pulsatility index (PI) for monitoring GnRHa therapy in girls with precocious puberty.

Methods: This is a retrospective cohort study of girls with central precocious puberty (CPP) and early and fast puberty (EFP) treated with GnRHa. We included girls who underwent pelvic ultrasound and Doppler imaging of the uterine arteries before and during therapy. Analyses included uterine artery PI and uterine, endometrial, and ovarian measurements. Receiver operating characteristic (ROC) curves with cutoffs determined by the Youden index were used for data analysis.

Results: In total, 28 pairs of PI measurements (54% of girls with CPP, 46% with EFP) before and during GnRHa therapy were included in the paired-sample analysis. The median duration of treatment at the time of ultrasound was 11.5 (7; 19) months. The mean PI was significantly higher during GnRHa therapy than at baseline (6.5 ± 1.8 vs. 4.0 ± 1.6, respectively, P < 0.001). A total of three girls met clinical and laboratory criteria for treatment failure. ROC curve analysis showed that the PI was able to identify an effective GnRHa therapy with a mean area under the curve (AUC) of 0.967 ± 0.04 (P < 0.001), and the PI cutoff point of 5.4 held a sensitivity of 84%, specificity of 100%, and accuracy of 86%.

Conclusion: We found a significant increase in the PI during GnRHa therapy, which reflects higher resistance in the blood flow to the uterus, indicating effective pubertal hormone suppression.

Introduction: Chronic social isolation (CSI) stress leads to numerous maladaptive changes in physiology and psychology, however, very little is known about the effects of longer time-scale CSI and there are divergent views regarding the underlying mechanisms. This study aimed to elucidate the common neuroendocrine mechanisms underlying the maladaptive changes caused by 14-week (14wk-) and 20-week (20wk-) CSI.

Methods: We investigated the impacts of 14wk- and 20wk- CSI on anxiety/depression-like behaviors in male C57BL/6N mice with classical behavioral tests, and the immunofluorescence method was used for quantification of the arginine vasopressin (AVP)/Oxytocin (OT) positive neurons in the PVN and screening out the differential activation brain regions (DABrs) on exposure of tail suspension. The expression of Avpr1a and Oxtr in the lateral septum dorsal (LSD) was assessed by quantitative RT-PCR (qPCR), and the function of LSD Avpr1a+/+ neurons in emotion regulation was verified with pharmacological approaches. The concentration of AVP/OT in plasma was examined with the Enzyme-linked immunosorbent assay (ELISA).

Results: 14wk- and 20wk- CSI increased anxiety/depression-like behaviors and altered levels of exploratory locomotion in opposite directions, which are likely due to an imbalance of the AVP/OT system within the PVN and peripheral plasma, differential activation of LSD and thalamic brain regions, and abnormal expression of Avpr1a in LSD. Pharmacological results demonstrated that Avpr1a receptor in the LSD were involved in emotion regulation.

Conclusion: This study suggests that the imbalance of the AVP/OT system and the dysfunction of Avpr1a+/+ neurons in the LSD were engaged in common neuroendocrinology mechanisms for anxiety/depression induced by long-term CSI.

Adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) are essential regulators of cortisol production within the hypothalamic-pituitary-adrenal (HPA) axis. Elevated cortisol levels, resulting from excessive ACTH, can lead to Cushing's syndrome, a condition with significant morbidity. Neuroendocrine tumors (NETs) can ectopically produce both ACTH and CRH, contributing to this syndrome. This review discusses the pathophysiology, types, clinical presentation, diagnosis, and management of these tumors. Emphasis is placed on the importance of identifying dual CRH/ACTH secretion, which complicates diagnosis and necessitates tailored therapeutic strategies. Furthermore, the review highlights the prognosis, common complications, and future directions for research in this area. We report the case of a 53-year-old female patient who presented with severe Cushing's syndrome and was diagnosed with ectopic ACTH syndrome. Despite initial indications pointing towards pituitary-dependent hypercortisolism, further investigations revealed the presence of a highly differentiated atypically located tumor in the upper lobe of the left lung, adjacent to the mediastinum. Immunohistochemistry of the tumor tissue demonstrated not only ACTH but also CRH and CRH-R1 expression. The simultaneous expression of these molecules supports the hypothesis of the presence of a positive endocrine feedback loop within the NET, in which the release of CRH stimulates the expression of ACTH via binding to CRH-R1. This case report highlights the challenges in diagnosing and managing ectopic ACTH syndrome, emphasizing the importance of a comprehensive diagnostic approach to identify secondary factors impacting cortisol production, such as CRH production and other contributing neuroendocrine mechanisms.

Background: Neuroendocrine neoplasms (NENs) are comparatively rare tumours. However, prevalence is increasing steeply, related to rising incidence, earlier detection, and prolonged survival in many cases of metastatic NENs; with implications on health care resources.

Summary: This commentary/narrative review extracts the relatively scare, available literature related to costs of NEN cancer care, which is mainly based on studies performed in the Unites States. Key, now implemented or evolving NEN related treatment options over the last 15 years are summarised. The commentary further highlights in part preventable aspects that can further contribute to cost pressure in NEN cancer care, including issues related to inappropriate use of available diagnostic tools; and not considering differential diagnoses when assessing people with suspected carcinoid syndrome - with these risks being minimised with access to centres with multi-specialty expertise in the management of people with NENs. Issues observed in people with exocrine and/or endocrine pancreatic deficiencies caused by a NEN or treatment of the NEN are mentioned, as well as some specific aspects related to diagnostics involving 68Ga PET-CT scans and treatment with Lutetium peptide-receptor radionuclide therapy (Lu-PRRT).

Key messages: This commentary summarises factors influencing cost of NEN cancer care, and highlights in part preventable issues mostly related to delayed involvement of a NEN multidisciplinary team, observed in a UK NEN referral centre (ENETS Centre of Excellence certified since 2015) over the last 15 years; resulting in sub-optimal management of people with NENs and ultimately adding to cost pressure.

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from neuroendocrine cells, exhibiting a wide range of behaviors from indolent to highly aggressive forms. Treatment options remain limited, particularly for progressive cases. Cabozantinib, a multitarget tyrosine kinase inhibitor, has demonstrated potential in targeting key pathways related to tumor growth, angiogenesis, and metastasis.

Summary: This review provides a comprehensive analysis of cabozantinib's therapeutic role across various NEN subtypes, including gastroenteropancreatic NENs, lung NENs, pheochromocytomas/paragangliomas, Merkel cell carcinoma, presacral NENs, pituitary neuroendocrine tumors, and neuroendocrine prostate cancer.

Key messages: The paper discusses several preclinical and clinical studies that demonstrate the efficacy of cabozantinib in slowing tumor progression and improving progression-free survival, particularly in patients with progressive, well-differentiated NENs. However, cabozantinib's complex toxicity profile limits its broad application, necessitating further research to optimize dosing, particularly in syndromic NENs. Ongoing trials are investigating cabozantinib in combination with somatostatin analogs, peptide receptor radionuclide therapy, temozolomide, and immunotherapies in order to overcome treatment resistance and expanding therapeutic strategies for advanced NENs.

Background: Polycystic ovary syndrome (PCOS) is a complex condition with unclear mechanisms, posing a challenge for prevention and treatment of PCOS. The role of the hypothalamus and pituitary gland in regulating female reproduction is critical. Abnormalities in the hypothalamus and pituitary can impair reproductive function. It is important to study hypothalamic and pituitary changes in patients with PCOS.

Summary: This article reviews articles on the hypothalamus and PCOS with the goal of summarizing what abnormalities of the hypothalamic-pituitary-ovarian axis are present in patients with PCOS and to clarify the pathogenesis of PCOS. We find that the mechanisms by which the hypothalamus and pituitary regulate reproduction in girls are complex and are associated with altered sex hormone levels, obesity, and insulin resistance. Different animal models of PCOS are characterized by different alterations in the hypothalamus and pituitary and respond differently to different treatments, which correspond to the complex pathogenesis of patients with PCOS.

Key messages: Arcuate nucleus (ARC) is associated with luteinizing hormone (LH) surges. Suprachiasmatic nucleus, ARC, and RP3V are associated with LH surges. Animal models of PCOS have different characteristics.