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.

Peripheral nerve injuries, such as sciatic nerve transection (SNT), are associated with significant sensory and motor deficits. Growth hormone (GH) and gonadotropin-releasing hormone (GnRH) have been shown to exert neurotrophic effects that can promote nerve regeneration and functional reinnervation. However, the combined impact of these hormones on peripheral nerve repair remains poorly understood. This study aimed to analyze the individual and combined effects of GH and GnRH in a rat model of SNT, using orchiectomized male rats to prevent steroid-mediated neuroregeneration and neuroprotection. Treatments included GH, GnRH, or a combination of both, with subsequent assessments of motor and sensory function, as well as histological and molecular analyses of the nerve tissue and associated muscles. The results revealed that both GH and GnRH significantly enhanced nerve regeneration and neural function when administered individually. Treated animals exhibited improved axonal growth, myelination, as well as sensory and motor functional recovery. In addition, GH and GnRH reduced neuroinflammation/reactive gliosis, as evidenced by the downregulation of TNFα IL-1β, Iba-1 and GFAP, which are typically elevated following nerve injury. These findings indicate that each hormone independently supports critical aspects of nerve repair and functional restoration after injury. Surprisingly, when GH and GnRH were administered together, their beneficial effects were not additive. Instead, the combination of the two treatments led to diminished outcomes in comparison to either treatment alone. Specifically, animals receiving the combined therapy showed reduced axonal organization, impaired myelination, and less functional improvement. In conclusion, GH and GnRH demonstrate potential as individual therapeutic agents for promoting nerve regeneration, each providing significant benefits in terms of axonal growth, functional recovery, and reduction of neuroinflammation.

Chronic cocaine exposure results in changes in circulating steroid hormones, which is known to be associated with cocaine-seeking and cocaine-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.

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.

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 Incidence of neuroendocrine neoplasms (NEN) is rising globally, yet clinical and genetic factors remain poorly understood. Evidence for the role of obesity is conflicted and studies on prospectively collected data is sparse. We aimed to identify clinical and germline genetic risk factors associated with NEN in the UK Biobank. Methods Cases of NEN were identified in the UK Biobank's cancer registry data (N~500,000). Using a combination of ICD-O3 codes for cancer site and histology, NEN cases were stratified into neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC) and small / large cell lung cancer (SLCLC). A Cox-proportional hazards model was used to test for an association between clinical phenotypes and increased NEN risk, and a gene burden test in Regenie was used to test for causal variants in the exome sequencing data. Results We identified 704 NET, 340 NEC, and 550 SLCLC cases. Obesity (body mass index or waist-hip-ratio) and lower cholesterol (LDL, HDL or total) had a significantly significant association with NEN risk, however the effect size was marginal. Smoking and HbA1c associated only with SLCLC. Air pollution was not significantly associated when adjustment was made for socio-economic status. We replicated a known germline association between loss of function variants in MEN-1 and NEC, but did not detect any novel association in exome variants. Discussion This is the first large prospective population-based study to identify potential clinical and genetic risk factors for NEN and defined a novel phenotype in the UK Biobank. More research is needed to establish whether these relationships are causal. The exome study was underpowered, and future work in this area should focus on meta-analysing multiple large datasets.

Because prolactin excess and hyperthyroidism are often complicated by hyperglycemia and impaired insulin sensitivity, many patients with both these disorders are treated with metformin. This drug inhibits secretory function of overactive anterior pituitary cells, including lactotrophs. The purpose of the current study was to investigate whether metformin action on prolactin oversecretion is impacted by coexisting hyperthyroidism.

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.

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 healthcare resources.

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 associated with significant morbidity. Neuroendocrine tumors (NETs) can ectopically produce both ACTH and CRH, a rare phenomenon that further contributes to this syndrome.

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.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated neuroprotective effects and hold potential advantages in enhancing cognitive function. This study aimed to clarify the association between SGLT2 inhibitors and the risk of dementia among individuals diagnosed with type 2 diabetes (T2D).

Although neuroendocrine neoplasms (NENs) have a good prognosis, distant metastasis remains a crucial prognostic factor. Survivin, a tumor-associated antigen, is overexpressed in several solid tumors, indicating poor prognosis. We aimed to evaluate the clinical significance and role of survivin as a therapeutic target for NEN.

Obesity may lead to cognitive impairment and neuropsychiatric disorders, which are associated with changes in the brain cortical structure, particularly in cortical thickness. However, the exact genetic association between obesity and brain cortical thickness remains inconclusive. We aimed to identify the relationship between obesity-related traits (body mass index [BMI], waist-hip ratio [WHR], and waist-hip ratio adjusted for BMI [WHRadjBMI]) and brain cortical thickness.

Indoleamine 2,3-dioxygenase (IDO) converts L-tryptophan (T) to L-kynurenine (K) resulting in an immunosuppressive microenvironment. The aim of the current study was to evaluate in patients with neuroendocrine tumor (NET) (1) T and K concentrations; (2) correlation with clinical outcome; (3) relationship between IDO activity and inflammatory cytokines.

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.

Temozolomide (TMZ), a nonclassical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs).

The gut microbiome, allegedly involved in both healthy homeostasis and development of disease, is found to be associated with several types of cancer. Short-chain fatty acids (SCFAs), important metabolites derived from the gut microbiota, are described to carry both protective and promoting features in cancer development. Limited research exists on neuroendocrine tumors (NETs) and their association with microbiota-derived SCFAs. The aim of this study was to investigate possible alterations in plasma SCFAs/organic acids in NET patients compared to healthy controls.

Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide) or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptom control and antiproliferative effects in subsets of NET patients and this was associated with the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2, and SSTR3 and thus should respond to agonists targeting SSTR3.

Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However, environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition and adult eating behavior, metabolic phenotype, and cognitive abilities.