A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

CONTEXT: Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. OBJECTIVE: The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. DESIGN: A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. RESULTS: Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. CONCLUSIONS: The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Self-limited acute hepatotoxicity caused by pegvisomant.

We present a case of acute severe hepatitis in a patient with acromegaly receiving combination therapy with somatostatin analogs and pegvisomant. Hepatitis resolved completely 18 weeks after diagnosis of hypertransaminasemia without discontinuation of therapy and with a close clinical and biochemical follow-up. In this case, despite the severity of the hepatitis, therapy could be continued as hypertransaminasemia was gradually decreasing after the maximum peak. We also review the literature on toxic hepatitis associated to pegvisomant therapy analyzing the etiology, clinical predisposing factors and natural evolution.

[Patients in treatment for malnutrition in primary care, study of 500 real patients]. / Pacientes en tratamiento por desnutrición en atención primaria, estudio sobre 500 pacientes reales.

OBJECTIVE: The worsening of the nutritional status of certain segments of the population has led to frequent situations of chronic undernourishment even in the healthy population. There are very few data available on the prevalence and causes of malnutrition in Primary Health Care. The present study attempts to provide measurable information, obtained at random from the doctors involved in the country's Primary Health Care, on the characteristics of the undernourished patients, the cause of the undernourishment, the diagnostic means used, the treatment applied and the progress of the patients regularly treated in Primary Health Care facilities. MATERIALS AND METHOD: A sample of 1,819 doctors in Primary Health Care were surveyed to know their opinions on the nutritional status of their patients. They were asked to complete a "Patient Record" for the first patient to enter their office suffering from undernourishment. A total of 505 Patient Records were received from the different Primary Health Care doctors taking part in the study throughout Spain. RESULTS: Of the patients included, 10% were aged less than 10, while 46.7% were between 16 and 65 years of age and 44.2% were over 65. The main diagnosis in these patients was varied, with cancer patients (22.6%) and anorexics, including anorexia nerviosa and other non-oncological causes, (16.4%) the most common. As for the tests used for diagnosing undernourishment, those most frequently applied were physical examination (61%) and biochemical tests (56.4%). The risk factor most commonly found in these patients was old age/senility (21%). Nutritional support (55.8%) and dietary recommendations (45.3%) were the therapies most often applied. Only 47% of patients correctly implemented their treatment according to the doctors in Primary Health Care and the prognosis was as follows: 31% were expected to improve, 20% to worsen and 44% of cases would remain stable. CONCLUSIONS: From this study, it is concluded that most undernourished patients in Primary Health Care are there due to a severe pathology or because of age; that anthropometric and biochemical methods are used for diagnosis purposes although the clinical interview is of basic importance; that a large proportion of patients require some type of nutritional supplements; and finally that, according to the doctors, the expectations of improvement in the nutritional status of these patients are not good.

Pacientes en tratamiento por desnutrición en atención primaria, estudio sobre 500 pacientes reales / Patients receiving treatment for undernourishment in primary health care, study of 500 real patients

Objetivo: El empeoramiento del estado nutricional de algunos segmentos de la población ha provocado que las situaciones de desnutrición crónica sean frecuentes incluso en población sana. Se disponen de muy pocos datos de prevalencia y causas de malnutrición en atención primaria. En este estudio se pretende aportar una información mesurable, obtenida de manera aleatoria entre los médicos de atención primaria del país sobre las características de los pacientes desnutridos, la causa de la desnutrición, los medios empleados en el diagnóstico, el tratamiento empleado y la evolución de los pacientes tratados de manera habitual en las consultas de atención primaria. Material y método: A una muestra de 1.819 médicos de atención primaria a los que se les realizó una encuesta de opinión acerca el estado nutricional de sus pacientes, se les pidió que rellenaran una "Ficha paciente" del primer paciente con desnutrición que entrara en su consulta. Se obtuvieron un total de 505 "Ficha paciente" distribuidas entre los diferentes médicos de atención primaria participantes en el estudio en toda España.Resultados: Un 10 por ciento de los pacientes incluidos eran menores de 10 años, mientras que un 46,7 por ciento se hallaban entre los 16 y los 65 años y el 44,2 por ciento eran mayores de 65.El diagnóstico principal de los pacientes era variado, siendo los pacientes oncológicos (22,6 por ciento) y los pacientes anoréxicos (incluyendo anorexia nerviosa y otras causas no oncológicas) (16,4 por ciento) los más frecuentes. En cuanto a las pruebas realizadas para el diagnóstico de la desnutrición, las más frecuentemente usadas fueron el examen físico (61 por ciento) y las pruebas bioquímicas (56,4 por ciento). El factor de riesgo más frecuentemente encontrado en estos pacientes fue la tercera edad/senilidad (21 por ciento). Los soportes nutricionales (55,8 por ciento) y las recomendaciones dietéticas (45,3 por ciento) fueron los tratamientos más comúnmen te aplicados. Sólo un 47 por ciento de los paciente realizaban correctamente el tratamiento según sus médicos de atención primaria y el pronóstico de los mismos era a mejorar en un 31 por ciento, a empeorar en un 20 por ciento y mantenerse estable en el 44 por ciento de los casos.Conclusiones: De este estudio se extrae que la mayoría de los pacientes desnutridos en atención primaria lo están debido a una patología grave o a causa de la edad, que se emplean metodos antropométricos y bioquímicos pero fundamentalmente la entrevista clínica para diagnosticarlos, que un elevado porcentaje de los pacientes requieren suplementos nutricionales de algún tipo, y por último que las expectativas de mejoría del estado nutricional de estos pacientes según sus médicos, no son buenas (AU)

Objective: The worsening of the nutritional status of certain segments of the population has led to frequent situations of chronic undernourishment even in the healthy population. There are very few data available on the prevalence and causes of malnutrition in Primary Health Care. The present study attempts to provide measurable information, obtained at random from the doctors involved in the country’s Primary Health Care, on the characteristics of the undernourished patients, the cause of the undernourishment, the diagnostic means used, the treatment applied and the progress of the patients regularly treated in Primary Health Care facilities. Materials and Method: A sample of 1,819 doctors in Primary Health Care were surveyed to know their opinions on the nutritional status of their patients. They were asked to complete a “Patient Record” for the first patient to enter their office suffering from undernourishment. A total of 505 Patient Records were received from the different Primary Health Care doctors taking part in the study throughout Spain. Results: Of the patients included, 10% were aged less than 10, while 46.7% were between 16 and 65 years of age and 44.2% were over 65. The main diagnosis in these patients was varied, with cancer patients (22.6%) and anorexics, including anorexia nerviosa and other non-oncological causes, (16.4%) the most common. As for the tests used for diagnosing undernourishment, those most frequently applied were physical examination (61%) and biochemical tests (56.4%). The risk factor most commonly found in these patients was old age / senility (21%). Nutritional support (55.8%) and dietary recommendations (45.3%) were the therapies most often applied. Only 47% of patients correctly implemented their treatment according to the doctors in Primary Health Care and the prognosis was as follows: 31% were expected to improve, 20% to worsen and 44% of cases would remain stable. Conclusions: From this study, it is concluded that most undernourished patients in Primary Health Care are there due to a severe pathology or because of age; that anthropometric and biochemical methods are used for diagnosis purposes although the clinical interview is of basic importance; that a large proportion of patients require some type of nutritional supplements; and finally that, according to the doctors, the expectations of improvement in the nutritional status of these patients are not good (AU)

[Patients at risk for malnutrition in primary care. Social and health study]. / Pacientes en riesgo de desnutrición en asistencia primaria. Estudio sociosanitario.

GOALS: The worsening nutritional condition of certain population segments is an ever more frequent situation. Malnutrition also has considerable consequences, both in healthy individuals and in patients, leading to an increase in morbidity/mortality among the general population. The purpose of the present study is to learn the opinion of doctors in primary health care about the frequency of patients at risk of malnutrition attending their clinics; the most common forms of diagnostic technique used, the groups of population and situations that show the greatest risk of malnutrition as well as the therapeutic actions undertaken. MATERIALS AND METHODS: The present study effected 1819 opinion polls of primary health care doctors, distributed in proportion to the provincial distribution of doctors throughout Spain. With a margin of error of +/- 2.3% and a confidence interval of 95.5% (K-2). RESULTS: Of the patients seen in primary health care centres, 11% are at risk of malnutrition and approximately 61% of the total are detected at the medical clinic. The situations with the greatest risk are advanced age (71%), marginalized population (drug abusers, alcoholics) (56%), anorexia (50%), patients with mental disorders (42%), oncological pathologies (41%) and prolonged confinement in bed (39%). The therapeutic attitudes considered most appropriate by primary health care practitioners are a greater attention to diets and the use of nutritional supports in cases of established malnutrition. CONCLUSIONS: The present study reflects a high incidence of malnutrition risk among patients attending primary health care clinics (11%); and highlights the importance, from the point of view of preventive medicine, of improving nutritional education among professionals, as well as the availability of simple therapeutic actions and support measures that might help to avoid larger-scale problems with a large social and financial cost.

Pacientes en riesgo de desnutrición en asistencia primaria. Estudio sociosanitario / Patients at risk of malnutrition in primary health care. Social and health study

Objetivos: El empeoramiento del estado nutricional en algunos segmentos de la población, es un hecho cada vez más frecuente. La malnutrición, a su vez, tiene importantes consecuencias, tanto en individuos sanos como en enfermos provocando un aumento de la morbimortalidad de la población. El objetivo de este estudio es conocer la opinión de los médicos de atención primaria en cuanto a la frecuencia de pacientes en riesgo de desnutrición en su consulta; las formas de diagnóstico más empleadas, los grupos de población y situaciones que presentan mayor riesgo de desnutrición, y las acciones terapéuticas llevadas a cabo. Materiales y métodos: En este sentido se realizaron 1.819 encuestas de opinión a médicos de atención primaria, distribuidos de forma proporcional a la distribución provincial de médicos en España. Con un margen de error de ñ 2,3 por ciento y un nivel de confianza de 95,5 por ciento (K = 2).Resultados: El 11 por ciento de los pacientes vistos en atención primaria están en riesgo de desnutrición, y se suelen detectar en un 61 por ciento del total en la consulta médica. Las situaciones con mayor riesgo de desnutrición son la edad avanzada (71 por ciento), la población marginada (drogadicción, alcoholismo) (56 por ciento), la anorexia (50 por ciento), los pacientes con trastornos psíquicos (42 por ciento), la patología oncológica (41 por ciento), y el encamamiento prolongado (39 por ciento). Las actitudes terapéuticas consideradas más adecuadas por los médicos de atención primaria son un mayor cuidado de las dietas y el uso de soportes nutricionales en los casos de desnutrición establecida. Conclusiones: Este estudio refleja una alta incidencia del riesgo de desnutrición en la consulta de atención primaria (11 por ciento); y resalta la importancia desde un punto de vista preventivo de mejorar la educación nutricional de los profesionales, así como la disponibilidad de soportes y acciones terapéuticas sencillas que ayudarían a evitar problemas de mayor magnitud y de alto coste social y económico (AU)

Goals: The worsening nutritional condition of certain population segments is an ever more frequent situation. Malnutrition also has considerable consequences, both in healthy individuals and in patients, leading to an in crease in morbidity/mortality among the general population. The purpose of the present study is to learn the opinion of doctors in primary health care about the frequency of patients at risk of malnutrition attending their clinics; the most common forms of diagnostic technique used, the groups of population and situations that show the greatest risk of malnutrition as well as the therapeutic actions undertaken. Materials and Methods: The present study effected 1819 opinion polls of primary health care doctors, distributed in proportion to the provincial distribution of doctors throughout Spain. With a margin of error of ± 2.3% and a confidence interval of 95.5% (K-2). Results: Of the patients seen in primary health care centres, 11% are at risk of malnutrition and approximately 61% of the total are detected at the medical clinic. The situations with the greatest risk are advanced age (71%), marginalized population (drug abusers, alcoholics) (56%), anorexia (50%), patients with mental disorders (42%), oncological pathologies (41%) and prolonged confinement in bed (39%). The therapeutic attitudes considered most appropriate by primary health care practitioners are a greater attention to diets and the use of nutritional supports in cases of established malnutrition. Conclusions: The present study reflects a high incidence of malnutrition risk among patients attending primary health care clinics (11%); and highlights the importance, from the point of view of preventive medicine, of improving nutritional education among professionals, as well as the availability of simple therapeutic actions and support measures that might help to avoid larger-scale problems with a large social and financial cost (AU)