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1.
Predictors of biochemical response to somatostatin receptor ligands in acromegaly.
Marazuela, M, Martínez-Hernandez, R, Marques-Pamies, M, Biagetti, B, Araujo-Castro, M, Puig-Domingo, M
Best practice & research. Clinical endocrinology & metabolism. 2024;(4):101893
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Abstract
Although predictors of response to first-generation somatostatin receptor ligands (fg-SRLs), and to a lesser extent to pasireotide, have been studied in acromegaly for many years, their use is still not recommended in clinical guidelines. Is there insufficient evidence to use them? Numerous biomarkers including various clinical, functional, radiological and molecular markers have been identified. The first ones are applicable pre-surgery, while the molecular predictors are utilized for patients not cured after surgery. In this regard, factors predicting a good response to fg-SRLs are specifically: low basal GH, a low GH nadir in the acute octreotide test, T2 MRI hypointensity, a densely granulated pattern, high immunohistochemistry staining for somatostatin receptor 2 (SSTR2), and E-cadherin. However, there is still a lack of consensus regarding which of these biomarkers is more useful or how to integrate them into clinical practice. With classical statistical methods, it is complex to define reliable and generalizable cut-off values for a single biomarker. The potential solution to the limitations of traditional methods involves combining systems biology with artificial intelligence, which is currently providing answers to such long-standing questions that may eventually be finally included into the clinical guidelines and make personalized medicine a reality. The aim of this review is to describe the current knowledge of the main fg-SRLs and pasireotide response predictors, discuss their current usefulness, and point to future directions in the research of this field.
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Early nutritional risk detection and intervention in COVID-19 hospitalized patients through the implementation of electronic automatized alarms.
Ramos, A, Joaquin, C, Ros, M, Martin, M, Cachero, M, Sospedra, M, Martínez, E, Socies, G, Pérez-Montes de Oca, A, Sendrós, MJ, et al
Endocrinologia, diabetes y nutricion. 2024;(2):71-76
Abstract
INTRODUCTION Hospitalized COVID-19 patients may present acute malnutrition which could influence morbidity and mortality. In the first wave of the pandemic severe weight loss was observed in many hospitalized patients. This pilot study evaluates the usefulness of an electronic automatized alarm for the early quantification of a low food intake as a predictor of the risk of malnutrition using COVID-19 disease as a model of severe illness. METHODS Observational prospective nutritional screening with a daily automatized warning message to the Endocrinology and Nutrition Service provided by the Information Systems. All adult patients admitted for COVID-19 from November 2020 to February 2021 were included. When diet intake was <50% during consecutive 48h, an automated message was generated identifying the patient as "at nutritional risk (NR)" and additional specialist nutritional evaluation and therapy was performed within the next 24h. RESULTS 205 patients out of 1176 (17.4%) were detected by automatized alarm and were considered as presenting high NR; 100% were concordant by the validated nutritional screening SNAQ. Nutritional support after detection was: 77.6% dietary adaptation+oral supplements; 9.3% enteral nutrition (EN); 1.5% parenteral nutrition (PN); 1% EN+PN and 10.7% no intervention is performed due to an end-of-life situation. Median weight loss during admission was 2.5kg (p25 0.25-p75: 6kg). Global mortality was 6.7% while in those detected by automatized alarm was 31.5%. CONCLUSIONS The implementation of an electronic NR screening tool was feasible and allowed the early nutritional assessment and intervention in COVID-19 hospitalized patients and can be useful in patients hospitalized for other pathologies.
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Prolactin and Growth Hormone Signaling and Interlink Focused on the Mammosomatotroph Paradigm: A Comprehensive Review of the Literature.
Araujo-Castro, M, Marazuela, M, Puig-Domingo, M, Biagetti, B
International journal of molecular sciences. 2023;(18)
Abstract
Prolactin (PRL) and growth hormone (GH) are peptide hormones that bind to the class 1 cytokine receptor superfamily, a highly conserved cell surface class of receptors. Both hormones control their own secretion via a negative autocrine loop in their own mammosomatotroph, lactotroph or somatotroph. In this regard, GH and PRL are regulated by similar signaling pathways involving cell growth and hormone secretion. Thus, GH and PRL dysregulation and pituitary neuroendocrine tumor (PitNET) development may have common pathogenic pathways. Based on cell linage, lactotroph and somatotroph PitNETs come from pituitary-specific POU-class homeodomain transcription factor (Pit-1). Mammosomatotroph and plurihormonal PitNETs are a unique subtype of PitNETs that arise from a single-cell population of Pit-1 lineage. In contrast, mixed somatotroph-lactotroph PitNETs are composed of two distinct cell populations: somatotrophs and lactotrophs. Morphologic features that distinguish indolent PitNETs from locally aggressive ones are still unidentified, and no single prognostic parameter can predict tumor aggressiveness or treatment response. In this review, we aim to explore the latest research on lactotroph and somatotroph PitNETs, the molecular mechanisms involved in PRL and GH axis regulation and the signaling pathways involved in their aggressiveness, particularly focused on mammosomatotroph and mixed subtypes. Finally, we summarize epidemiological, clinical, and radiological features of these exceptional tumors. We aim to shed light, from basic to clinical settings, on new perspectives and scientific gaps in this field.
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Predictors of Response to Treatment with First-Generation Somatostatin Receptor Ligands in Patients with Acromegaly.
Marques-Pamies, M, Gil, J, Jordà, M, Puig-Domingo, M
Archives of medical research. 2023;(8):102924
Abstract
BACKGROUND AND AIMS Predictors of first-generation somatostatin receptor ligands (fgSRLs) response in acromegaly have been studied for over 30 years, but they are still not recommended in clinical guidelines. Is there not enough evidence to support their use? This systematic review aims to describe the current knowledge of the main predictors of fgSRLs response and discuss their current usefulness, as well as future research directions. METHODS A systematic search was performed in the Scopus and PubMed databases for functional, imaging, and molecular predictive factors. RESULTS A total of 282 articles were detected, of which 64 were included. Most of them are retrospective studies performed between 1990 and 2023 focused on the predictive response to fgSRLs in acromegaly. The usefulness of the predictive factors is confirmed, with good response identified by the most replicated factors, specifically low GH nadir in the acute octreotide test, T2 MRI hypointensity, high Somatostatin receptor 2 (SSTR2) and E-cadherin expression, and a densely granulated pattern. Even if these biomarkers are interrelated, the association is quite heterogeneous. With classical statistical methods, it is complex to define reliable and generalizable cut-off values worth recommending in clinical guidelines. Machine-learning models involving omics are a promising approach to achieve the highest accuracy values to date. CONCLUSIONS This survey confirms a sufficiently robust level of evidence to apply knowledge of predictive factors for greater efficiency in the treatment decision process. The irruption of artificial intelligence in this field is providing definitive answers to such long-standing questions that may change clinical guidelines and make personalized medicine a reality.
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Age-Related Hormones Changes and Its Impact on Health Status and Lifespan.
Biagetti, B, Puig-Domingo, M
Aging and disease. 2023;(3):605-620
Abstract
The increase in life expectancy is accompanied with an increased consultation of age-related pathologies including endocrine disorders. Two main areas are focusing the attention of medical and social research in older population: the diagnosis and care of this heterogeneous population, and the interventional measures potentially useful to mitigate age-related functional declines and to increase health and quality of lifespan. Thus, better understanding the physiopathology of aging and establishing accurate diagnostic and personalized approaches are a priority and currently an unmet need of the medical community. The endocrine system plays a major role in survival and lifespan through regulating vital processes such as energy consumption and optimizing the stress response among others. The aim of this paper is to review the physiological evolution of the main hormonal functions in aging and its clinical translation to improve our approach to the aging patient.
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ENDOCRINE OBESITY: Pituitary dysfunction in obesity.
Ruiz, S, Vázquez, F, Pellitero, S, Puig-Domingo, M
European journal of endocrinology. 2022;(6):R79-R92
Abstract
Obesity, the growing pandemic of the 21st century, is associated with multiple organ dysfunction, either by a direct increase in fatty organ content or by indirect modifications related to general metabolic changes driven by a specific increase in biologic products. The pituitary gland is not protected against such a situation. Different hypothalamic-pituitary axes experience functional modifications initially oriented to an adaptive situation that, with years of obesity, turn to maladaptive dynamics that contribute to perpetuating obesity and specific symptoms of their hormonal nature. This paper reviews the recent knowledge on obesity-related pituitary dysfunction and its pathogenic mechanisms and discusses potential therapeutic actions aimed at contributing to ameliorating the complex treatment of severe cases of obesity.
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Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer.
Pardo, JC, Ruiz de Porras, V, Gil, J, Font, A, Puig-Domingo, M, Jordà, M
Nutrients. 2022;(4)
Abstract
Prostate cancer (PCa) is the most commonly diagnosed malignant neoplasm in men in the Western world. Localized low-risk PCa has an excellent prognosis thanks to effective local treatments; however, despite the incorporation of new therapeutic strategies, metastatic PCa remains incurable mainly due to disease heterogeneity and the development of resistance to therapy. The mechanisms underlying PCa progression and therapy resistance are multiple and include metabolic reprogramming, especially in relation to lipid metabolism, as well as epigenetic remodelling, both of which enable cancer cells to adapt to dynamic changes in the tumour. Interestingly, metabolism and epigenetics are interconnected. Metabolism can regulate epigenetics through the direct influence of metabolites on epigenetic processes, while epigenetics can control metabolism by directly or indirectly regulating the expression of metabolic genes. Moreover, epidemiological studies suggest an association between a high-fat diet, which can alter the availability of metabolites, and PCa progression. Here, we review the alterations of lipid metabolism and epigenetics in PCa, before focusing on the mechanisms that connect them. We also discuss the influence of diet in this scenario. This information may help to identify prognostic and predictive biomarkers as well as targetable vulnerabilities.
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Factors associated with critical care requirements in diabetic patients treated with dexamethasone for COVID-19 infection in the first wave of the pandemia.
Batule, S, Soldevila, B, Figueredo, C, Julián, MT, Egea-Cortés, L, Reyes-Ureña, J, Casabona, J, Mateu, L, Paredes, R, Clotet, B, et al
Frontiers in endocrinology. 2022;:1009028
Abstract
INTRODUCTION Diabetes mellitus (DM) and hyperglycemia are important risk factors for poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to analyze the factors associated with the composite outcome of the necessity of invasive mechanical ventilation (IMV) or admission to the intensive care unit (ICU) in subjects with severe COVID-19 infection treated with dexamethasone comparing patients with DM vs. patients without DM. RESEARCH DESIGN AND METHODS An observational retrospective cohort study was performed, including hospitalized subjects with a diagnosis of SARS-CoV-2 pneumonia. Inclusion criteria were: age ≥18 years old with severe COVID-19 disease requiring daily intravenous 6 mg dexamethasone treatment for 10 days. Exclusion criteria were: <18 years old, non-severe illness and/or patients in charge of ICU. Variables related to clinical and analytical parameters, glycemic control, acquired-hospital superinfections, mortality, IMV requirement, ICU admission and length of stay were included. RESULTS Two hundred and nine individuals with COVID-19 disease treated with dexamethasone were included. One hundred twenty-five out of these subjects (59.8%) were patients with DM. Overall, from the 209 subjects, 66 (31.6%) required IMV or were admitted to the ICU, with significant differences between patients with DM (n=50) vs. patients without DM (n=16) (76% vs. 24%, p=0.002). Among the group of subjects with DM (n=125), those who required IMV or were admitted to the ICU showed higher serum concentrations of C-reactive protein, interleukin-6, D-dimer, ferritin and pro-calcitonin and significantly lower serum concentrations of albumin compared to those who did not require IMV or were not admitted to the ICU. Besides, between these two groups of patients with DM, we observed no differences in glycemic parameters, including median capillary blood glucose values, glycosylated hemoglobin, coefficient of variability and hypoglycemic episodes. In the multinomial analysis, factors independently associated with the composite outcome of IMV or admission to the ICU in the insulin-treated group were the National Early Warning Score (NEWS) 2 score (OR 1.55 [1.17-2.17], p=0.005) and the presence of hospital-acquired superinfections (OR 35.21 [5.11-386.99], p=0.001). CONCLUSIONS In our study, parameters related to glycemic control were not associated with IMV requirement nor admission to the ICU in patients with DM and severe COVID-19 disease receiving daily 6 mg of dexamethasone for 10 days. However, hospital-acquired superinfections and disease severity at admission were independent factors associated with this composite outcome.
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Nutritional Status According to the GLIM Criteria in Patients with Chronic Heart Failure: Association with Prognosis.
Joaquín, C, Alonso, N, Lupón, J, Gastelurrutia, P, Pérez-Monstesdeoca, A, Domingo, M, Zamora, E, Socias, G, Ramos, A, Bayes-Genis, A, et al
Nutrients. 2022;(11)
Abstract
BACKGROUND The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). METHODS This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognostic power than the MNA. RESULTS Abnormal nutritional status was identified in 19.8% of the patients with the GLIM criteria and in 25.1% with the MNA. In the multivariate analyses (age, sex, NYHA functional class, diabetes, and Barthel index), nutritional status assessed by the MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalizations during the five-year follow-up. CONCLUSIONS Malnutrition assessed by MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalization in our cohort of outpatients with HF.
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Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?
Soldevila, B, Puig-Domingo, M, Marazuela, M
Reviews in endocrine & metabolic disorders. 2022;(2):137-150
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Abstract
Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.
