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Acromegaly is a hormonal disorder resulting from excessive growth hormone (GH) secretion frequently produced by pituitary adenomas and consequent increase in insulin‐like growth factor 1 (IGF‐I). Elevated GH and IGF‐I levels result in a wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Somatostatin analogues (SSAs) form the basis of medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy in patients undergoing unsuccessful surgery. However, a considerable percentage of patients do not respond to SSAs treatment. Somatostatin receptors (SSTR1‐5) and dopamine receptors (DRD1‐5) subtypes play critical roles in the regulation of hormone secretion. These receptors are considered important pharmacological targets to inhibit hormone oversecretion. It has been proposed that decreased expression of SSTRs may be associated with poor response to SSAs. Here, we systematically examine SSTRs and DRDs expression in human somatotroph adenomas by quantitative PCR. We observed an association between the response to SSAs treatment and DRD4, DRD5, SSTR1 and SSTR2 expression. We also examined SSTR expression by immunohistochemistry and found that the immunohistochemical detection of SSTR2 in particular might be a good predictor of response to SSAs.

Telemedicine has emerged as a promising tool to enhance adherence and monitoring in patients with eating disorders (EDs). Traditional face-to-face cognitive therapies remain the gold standard; however, integrating telemedicine may provide additional support and improve patient engagement and retention. Given the increasing use of digital health interventions, it is crucial to assess their safety and effectiveness in complementing conventional treatments. We aimed to evaluate the safety and effectiveness of telemedicine as a complementary tool for cognitive face-to-face therapies to promote adherence and monitoring of patients with EDs. We consulted the National Institute for Health and Care Excellence, the Canadian Agency for Drugs and Technologies in Health (now known as Canada's Drug Agency), MEDLINE (Ovid), Embase, Web of Science, Cochrane Library, international HTA database (International Network of Agencies for Health Technology Assessment), CINAHL (EBSCO), and PsycINFO (EBSCO) websites and databases in December 2024 to identify eligible systematic reviews, synthesis reports, or meta-analyses that address telemedicine as a complementary therapy to face-to-face care in patients with EDs. Two researchers performed an independent critical reading of the systematic reviews and assessed the risk of bias using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews, version 2). We initially identified 1004 studies, but only 5 (0.5%) systematic reviews met the inclusion criteria. Email, vodcasts, smartphone apps, and SMS text messaging were the principal telemedicine channels. Telemedicine interventions were safe, helpful, and motivating; improved retention rates and patient-physician communication; and reduced ED symptoms. Telemedicine interventions showed promising, positive findings as a complementary tool for face-to-face ED treatment that must be interpreted cautiously. The limited number of systematic reviews selected and their moderate to critically low quality underscore the need for further research in this area.

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.

Somatostatin receptor subtype 5 (SST5) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5‐AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5‐AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5‐AS1 expression was assessed by quantitative real‐time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5‐AS1 genes. Results revealed that SSTR5 and SSTR5‐AS1 were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5‐AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5‐AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response. Somatostatin receptor subtype 5 (SST5) is a key player in neuroendocrine tumors (NETs). Yet, its regulation is still insufficiently understood. This study presents original evidence that SSTR5 expression may be epigenetically regulated by the SSTR5‐AS1 antisense transcript and DNA methylation in pituitary and pancreatic NETs, providing a new regulatory layer influencing receptor levels and, thereby, tumor behavior and treatment response.

Craniopharyngiomas are rare benign pathologies but clinically challenging tumours because of their intimate relationship with critical brain structures, leading to severe endocrine-deficiencies/comorbidities. Therefore, identifying alternative prognostic/therapeutic tools is crucial. Although dysregulated splicing is a molecular feature that characterizes almost all tumour/cancer types, the dysregulation of the components belonging to the molecular machinery controlling the splicing-process (spliceosome) remains unknown in craniopharyngiomas. Here, we uncover a profound dysregulation in the expression of relevant spliceosome-components and splicing-factors in craniopharyngiomas versus control non-tumour tissues, identifying PRPF8 and RAVER1 as key tumour suppressor factors associated with relevant oncogenic processes. Moreover, we demonstrate that the spliceosome activity inhibition using pladienolide-B in primary patient´s derived cell-cultures might serve as a potential therapeutic tool worth to be explored in humans. Altogether, our results demonstrate a drastic and clinically relevant spliceosome-associated molecular dysregulation in craniopharyngiomas, which could serve as a potential source of novel diagnostic/prognostic biomarkers and therapeutic targets.

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.

Objective To describe the characteristics of the patients, as well as the treatment outcomes for the people treated in an Endocrinology and Nutrition unit with a diagnosis of SE-ED (> 7 years evolution despite evidence-based conventional treatment). Methods A descriptive observational study was conducted. Patients with a diagnosis of SE-ED (anorexia nervosa and bulimia nervosa) treated in the Endocrinology and Nutrition service of the Virgen del Rocío University Hospital between 2014 and 2019 were included. Results 67 patients were contacted and accepted to participate in the study. 95.5% were women. 67.2% were diagnosed with AN (anorexia nervosa) and 32.8% with BN (bulimia nervosa). Their median ages (years) at the onset of symptoms, beginning of follow-up and at present were 17, 32 and 42.5 respectively. Their median time of follow-up was 9 years. 73.1% had mental comorbitidy and AN patients had more osteoporosis (48.9% vs 22.7%, p  = 0.04) and hypogonadotropic hypogonadism (31.1% vs. 4.5%, p  = 0.014). Discussion The SE-ED patients in our sample began treatment years after the onset of symptoms, which may have led to their chronification. This emphasizes the importance of an early diagnosis in eating disorders. They presented with a high rate of physical complications and mental comorbidity. In the current sample, it was determined that patients with AN presented with higher rates of osteoporosis and hypogonadotropic hypogonadism than patients with BN. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies. Plain English summary At present, the criteria for severe and enduring eating disorders (SE-ED) are not sufficiently clearly defined. It has been calculated that approximately 20% of patients with anorexia nervosa (AN) and 10% of patients with bulimia nervosa (BN) suffer a chronification. We evaluated the characteristics of the patients, as well as the treatment outcomes for the people treated in an Endocrinology and Nutrition unit with a diagnosis of SE-ED (which was made based on an evolution greater than 7 years despite conventional treatment). The SE-ED patients in our sample began treatment years after the onset of symptoms, which may have led to their chronification. They presented with a high rate of physical complications and mental comorbidity. In the current sample, it was determined that patients with AN presented with higher rates of osteoporosis (health condition that weakens bones, making them fragile and more likely to break) and hypogonadotropic hypogonadism (illness in which testes or ovaries produce little or no sex hormones due to a problem in the pituitary gland) than patients with BN.

Background: This study addresses hypoglycemia in adults with inherited metabolic disorders (IMDs), highlighting the importance of intermittently scanned continuous glucose monitoring (isCGM). Despite the elevated risk of hypoglycemia in an important group of these diseases, the use of isCGM remains uncommon and there is limited evidence supporting its effectiveness. Methods: A longitudinal quasi-experimental study was performed in 18 adults with IMDs, evaluating the use of isCGM for 2 months. Time in hypoglycemia (TBR), hyperglycemia (TAR), and time in range (TIR) were monitored, in addition to symptomatic and asymptomatic hypoglycemic events. Follow-up visits were performed at 7 days, 14 days, and 2 months. Results: TBR < 70 mg/dL was significantly reduced from 1.5% at baseline to 0% at 2 months. A decrease in the number and duration of hypoglycemic events was also observed. In some IMD subgroups, isCGM enabled detection of asymptomatic hypoglycemia and adjustment to dietary management, improving glycemic control. Conclusions: isCGM is effective in detecting and reducing hypoglycemia in adults with IMDs, optimizing nutritional therapy, and improving the quality of life of patients and their families.

Abstract Context Pituitary neuroendocrine tumors (PitNETs) are a commonly underestimated pathology in terms of incidence and associated morbimortality. Currently, an appreciable subset of patients are resistant or poorly responsive to the main current medical treatments [i.e., synthetic somatostatin analogs (SSAs) and dopamine agonists]. Thus, development and optimization of novel and available medical therapies is necessary. Biguanides (metformin, buformin, and phenformin) are antidiabetic drugs that exert antitumoral actions in several tumor types, but their pharmacological effects on PitNETs are poorly known. Objective We aimed to explore the direct effects of biguanides on key functions (cell viability, hormone release, apoptosis, and signaling pathways) in primary cell cultures from human PitNETs and cell lines. Additionally, we evaluated the effect of combined metformin with SSAs on cell viability and hormone secretion. Design A total of 13 corticotropinomas, 13 somatotropinomas, 13 nonfunctioning PitNETs, 3 prolactinomas, and 2 tumoral pituitary cell lines (AtT-20 and GH3) were used to evaluate the direct effects of biguanides on cell viability, hormone release, apoptosis, and signaling pathways. Results Biguanides reduced cell viability in all PitNETs and cell lines (with phenformin being the most effective biguanide) and increased apoptosis in somatotropinomas. Moreover, buformin and phenformin, but not metformin, reduced hormone secretion in a cell type–specific manner. Combination metformin/SSA therapy did not increase SSA monotherapy effectiveness. Effects of biguanides on PitNETs could involve the modulation of AMP-activated protein kinase–dependent ([Ca2+]i, PI3K/Akt) and independent (MAPK) mechanisms. Conclusion Altogether, our data unveil clear antitumoral effects of biguanides on PitNET cells, opening avenues to explore their potential as drugs to treat these pathologies. Biguanides reduced aggressiveness features (e.g., proliferation, apoptosis) in pituitary neuroendocrine tumors, opening avenues to explore their potential as drugs to treat these pathologies.

Abstract Disclosure: E. Venegas moreno: None. A. Jimenez sanchez: None. P. Remon-Ruiz: None. M. Dios Fuentes: None. A. Soto: None. GOAL • To describe other hormone deficiencies and adverse events in a long-lasting cohort of 53 adults under growth hormone (GH) treatment. MATERIALS & METHODS • Transversal study. • Variables were retrospectively collected from the digital health record of the Virgen del Rocío University Hospital in August 2023. • Numerical variables are expressed as mean (standard deviation). Statistical significance was designated as a p-value < 0.05. • Elders defined as ≥ 65 years old. • IGF-1 reference values from our hormone laboratory: /div> Results: • 53 patients under treatment, 7 elders. • 49.35 (19.68) years old. • 22 (41.51%) men, 31 (58.49%) women. • 51 patients had hormonal deficits: - 43 (81.13%) LH/FSH. - 39 (73.58%) TSH. - 37 (69.81%) ACTH. - 10 (18.87%) AVP. /div> p-value = 0.043 /div> p-value = 0.037 /div> p-value = 0.042 /div> p-value = 0.035 • 16.18 (5.39) years in treatment. • 2 incident side effects (3.77%): 1 headache (continued), 1 dizziness (discontinued). • 12 incident benign tumors during treatment in 10 patients. /div> • 3 incident benign tumors before treatment in 3 patients. /div> • 4 incident neoplasms during treatment in 4 patients. /div> • Incident neoplasms before treatment: 0. • IGF-1 levels during treatment if: a. No tumor or neoplasms: 143.80 (53.75) ng/mL b. Tumor: 144.00 (40.83) ng/mL c. Neoplasm: 129.25 (49.28) ng/mL • In ANOVA analysis, we found no differences between groups regarding the variable \"tumor\" concerning IGF-1 (p-value=0.863) or age (p-value=0.813). • Age at the first tumor: 38.73 (17.98) years, at 9.93 (13.22) years under treatment. ConclusionS: • Pituitary tumors had the most co-secretory deficits. • A very low proportion of the sample developed side effects due to a biosimilar GH. • The number of neoplasms under treatment was low and comprised by skin cancers. • The development of tumors and neoplasms under treatment was not related to IGF-1 levels. Presentation: Saturday, July 12, 2025