Cognitive Functioning and Cortical Brain Thickness in Acromegaly Patients: A Pilot study.

OBJECTIVE: Cognitive effects in acromegaly patients are poorly understood and the mechanisms involved are still unclear. The aim of this study was to evaluate the cognitive function, depression, and quality of life of acromegaly patients treated with pegvisomant versus somatostatin analogues (SRLs) and to analyze the effect of the different treatments on cognition and possible structural brain changes. METHODS: This cross-sectional study involved 23 acromegaly patients divided into two groups according to treatment modality: One group of 9 patients treated with pegvisomant and another group of 14 patients treated with SRLs. All participants underwent blood analysis, neuropsychological tests, depression tests, quality of life assessment, and 3-Tesla magnetic resonance imaging. RESULTS: We found no significant differences between groups in the neuropsychological tests, depression or quality of life; nor in the whole-brain cortical thickness. In the SRL group, the volume of the thalamus correlated positively with executive function, a correlation not found in the pegvisomant group. In addition, the pegvisomant group had significantly higher levels of insulin than the SRL group. CONCLUSIONS: In conclusion, in this pilot study, the type of pharmacological treatment in patients with acromegaly and good glycemic control did not influence the cognitive function and cortical brain thickness. However, pegvisomant could play a neuroprotective role on the thalamus that will have to be demonstrated with larger samples in future studies.

Lixisenatida en pacientes con diabetes tipo 2 y obesidad: más allá del control glucémico / Lixisenatide in patients with type 2 diabetes and obesity: Beyond glycaemic control

OBJETIVO: Evaluar la tolerancia a lixisenatida y sus efectos sobre el peso y el control metabólico de pacientes con diabetes tipo 2 y obesidad. DISEÑO: Estudio prospectivo. Emplazamiento: Consultas de atención especializada de Endocrinología y Nutrición en Almería, Granada y Málaga. PARTICIPANTES: Pacientes con diabetes tipo 2 y obesidad. INTERVENCIONES: Respuesta y tolerancia al tratamiento con lixisenatida. Mediciones principales: Se analizaron datos clínicos y analíticos con medidas de cambio intrasujeto antes-después del tratamiento. RESULTADOS: Evaluamos 104 pacientes (51% mujeres) con diabetes tipo 2 y obesidad (Almería 18,3%; Granada 40,4%; Málaga 41,3%). Edad media 58,4±10,5 años y duración media de diabetes 11,2±6,7 años. El tiempo medio desde la visita basal a la revisión tras inicio de tratamiento con lixisenatida fue de 3,8±1,6 meses. Encontramos mejoría significativa del peso (p < 0,001), índice de masa corporal (p < 0,001), circunferencia de cintura (p = 0,002), presión arterial sistólica (p < 0,001) y diastólica (p = 0,001), glucemia en ayunas (p < 0,001), HbA1c (p = 0,022), colesterol total (p < 0,001), colesterol LDL (p = 0,046) y triglicéridos (p = 0,020). No se observó alteración de cifras de amilasa en relación con el tratamiento con lixisenatida, y el 7,9% no lo toleraron. CONCLUSIONES: Lixisenatida consigue: 1) mejoría significativa de parámetros antropométricos y control glucémico (glucemia basal y HbA1c); 2) descenso significativo de la presión arterial y del perfil lipídico, y 3) seguridad y buena tolerancia en la mayoría de los pacientes. Además, encontramos una significativa intensificación del tratamiento antihipertensivo e hipolipemiante

AIM: To evaluate tolerance to lixisenatide and its effects on weight and metabolic control in type 2 diabetes and obese patients. DESIGN: Prospective study. SETTING: Endocrinology clinics in Almeria, Granada and Malaga. PARTICIPANTS: Patients with type 2 diabetes and obesity. INTERVENTIONS: Response and tolerance to lixisenatide treatment. MAIN MEASUREMENTS: Clinical and analytical data of the subjects were evaluated at baseline and after treatment. RESULTS: The study included 104 patients (51% women) with type 2 diabetes and obesity (Almeria 18.3%; Granada 40.4%; Malaga 41.3%). The mean age was 58.4±10.5 years, and the mean duration of diabetes was 11.2±6.7 years. The patients were re-evaluated at 3.8±1.6 months after treatment with lixisenatide. Significant improvements were found in weight (P<.001), body mass index (P<.001), waist circumference (P=.002), systolic blood pressure (P<.001), diastolic blood pressure (P=.001), fasting glucose (P<.001), HbA1c (P=.022), Total cholesterol (P<.001), LDL-cholesterol (P=.046), triglycerides (P=.020), hypertension drugs (P<.001), and lipids drugs (P<.001). No changes were observed in levels of amylase related to lixisenatide treatment, and 7.9% of patients did not tolerate it. CONCLUSIONS: Lixisenatide achieved significant improvements in anthropometric parameters, glycaemic control (fasting glucose and HbA1c), blood pressure and lipids. It was safe and well tolerated in most patients. In addition, there was a significant increase in the use of antihypertensive and lipid-lowering therapy

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

[Lixisenatide in patients with type 2 diabetes and obesity: Beyond glycaemic control]. / Lixisenatida en pacientes con diabetes tipo 2 y obesidad: más allá del control glucémico.

AIM: To evaluate tolerance to lixisenatide and its effects on weight and metabolic control in type2 diabetes and obese patients. DESIGN: Prospective study. SETTING: Endocrinology clinics in Almeria, Granada and Malaga. PARTICIPANTS: Patients with type2 diabetes and obesity. INTERVENTIONS: Response and tolerance to lixisenatide treatment. MAIN MEASUREMENTS: Clinical and analytical data of the subjects were evaluated at baseline and after treatment. RESULTS: The study included 104 patients (51% women) with type2 diabetes and obesity (Almeria 18.3%; Granada 40.4%; Malaga 41.3%). The mean age was 58.4±10.5years, and the mean duration of diabetes was 11.2±6.7years. The patients were re-evaluated at 3.8±1.6months after treatment with lixisenatide. Significant improvements were found in weight (P<.001), body mass index (P<.001), waist circumference (P=.002), systolic blood pressure (P<.001), diastolic blood pressure (P=.001), fasting glucose (P<.001), HbA1c (P=.022), Total cholesterol (P<.001), LDL-cholesterol (P=.046), triglycerides (P=.020), hypertension drugs (P<.001), and lipids drugs (P<.001). No changes were observed in levels of amylase related to lixisenatide treatment, and 7.9% of patients did not tolerate it. CONCLUSIONS: Lixisenatide achieved significant improvements in anthropometric parameters, glycaemic control (fasting glucose and HbA1c), blood pressure and lipids. It was safe and well tolerated in most patients. In addition, there was a significant increase in the use of antihypertensive and lipid-lowering therapy.

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca2+ signaling ([Ca2+]i), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca2+]i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca2+]i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response.

Experiencia clínica con lixisenatida en pacientes con diabetes tipo 2 y obesidad en consultas de atención especializada en Málaga / Lixisenatide clinical experience on patients with type 2 diabetes and obesity in endocrinology offices in Malaga

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