ABSTRACT
Introducción: La enfermedad de Cushing (EC) es rara durante el embarazo y se asocia con complicaciones maternas y fetales significativas. El objetivo fue reportar el caso de una paciente con EC que logró embarazo y parto sin complicaciones tras el tratamiento con dosis bajas de cabergolina. Métodos: Mujer de 29 años con diagnóstico de EC (macroadenoma secretor de ACTH que produce desplazamiento del quiasma óptico, infiltra el seno cavernoso derecho y engloba la arteria carótida interna). Se somete a cirugía transesfenoidal con resección tumoral incompleta. Luego de un año de estabilidad clínica, reaparecen los síntomas por lo que se instaura tratamiento médico con cabergolina. Durante el tratamiento la paciente concibe embarazo y se suspende la medicación. Resultados: En el primer trimestre, los parámetros clínicos y bioquímicos indican EC activa, por lo que se decide reinstaurar Cabergolina a dosis bajas durante el resto de la gestación. Con el agonista dopaminérgico se alcanza normalizar parámetros clínicos y de laboratorio y la paciente dio a luz una niña sana a las 38 semanas, dentro de percentiles normales y sin complicaciones. Conclusión: El embarazo es un evento raro en pacientes con EC. Sin embargo, las consecuencias de la exposición materno-fetal al hipercortisolismo pueden ser graves. Nuestra experiencia con el uso de cabergolina a dosis bajas en una embarazada con EC, aporta datos favorables a los escasos reportes bibliográficos existentes, sumando evidencia sobre el perfil de seguridad del fármaco en esta población de pacientes.
Subject(s)
Pituitary ACTH Hypersecretion , Pregnancy , Female , Humans , Cabergoline , Tretinoin , Colectomy , Retrospective StudiesSubject(s)
Pituitary ACTH Hypersecretion , Pregnancy , Female , Humans , Cabergoline , Tretinoin , Colectomy , Retrospective StudiesABSTRACT
INTRODUCTION: Macroautophagy is a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles, with its regulation depending on autophagy-related proteins (Atg) and with Beclin1/Atg6 and microtubule-associated protein light chain 3 (LC3/Atg8) being key players in the mammalian autophagy. As reports on this mechanism in the field of pituitary neuropathology and neuroendocrinology are scarce, our study analyzed the ultrastructural signs of macroautophagy and the expression of Beclin1 and LC3 proteins in human functioning PitNETs and in experimental pituitary tumors. METHODS: A group of humans functioning PitNETs and an experimental lactotroph model in rats of the F344 strain stimulated with estradiol benzoate (BE) were used. Ultrastructural and molecular evidence of the macroautophagic process was evaluated using different techniques. RESULTS: In functioning PitNETs cohort, 60% exhibited evidence of macroautophagy, with a significant difference found for Beclin1 and LC3 between macro- and micro-PitNETs (p < 0.05). In the experimental model, the expression of both Beclin1 and LC3 proteins was immunopositive in normal and tumoral glands when analyzed by immunofluorescence, Western blot, and immunohistochemistry. In the experimental model, protein expression was associated with increased glandular size and weight. CONCLUSIONS: Our study revealed evidence of macroautophagy at the pituitary level and the important role of Beclin1 and LC3 in the progression of functioning PitNETs, implying that this mechanism participate in regulating pituitary cell growth.
Subject(s)
Macroautophagy , Pituitary Neoplasms , Humans , Rats , Animals , Beclin-1 , Rats, Inbred F344 , Autophagy , Microtubule-Associated Proteins/metabolism , Mammals/metabolismABSTRACT
Pituitary adenomas are intracranial neoplasms that originate from the adeno-pituitary cells, are mostly benign and slow growing. However, a small percentage can be aggressive and spread locally and / or remotely as malignancies. In recent years, progress has been made in understanding the biology of pituitary tumors, identifying mutations in the germline, somatic lines, and epigenetic mechanisms. Objective: review the updated bibliography on the mechanisms of pituitary tumorigenesis. Data source: bibliographic search was performed using the MEDLINE (PubMed), LILACS and Google Scholar databases since 2010 to April 2020. Conclusion: Knowledge and information on pituitary tumorogenesis mechanisms increased in recent decades, and new neoplastic pathways are recognized. However, there are currently few therapeutic approaches to act specifically on the underlying tumor genesis pathway identified in each case.
Los adenomas hipofisarios son neoplasias intracraneales que surgen de las células del lóbulo anterior de la glándula, benignos y de crecimiento lento en su gran mayoría. Sin embargo, un pequeño porcentaje puede mostrar un comportamiento clínicamente agresivo y diseminarse localmente y/o a distancia como verdaderas neoplasias malignas. Durante los últimos años, se observó un importante avance en el conocimiento de la biología de los tumores hipofisarios, identificándose mutaciones de las líneas germinal, somática y mecanismos epigenéticos. Objetivo: revisar la bibliografía actualizada sobre los mecanismos que contribuyen a la tumorogénesis hipofisaria. Fuente de datos: se realizó una búsqueda bibliográfica utilizando las bases de datos de MEDLINE (PubMed), LILACS y Google Scholar desde 2010 hasta abril de 2020. Conclusión: El conocimiento e información sobre los mecanismos asociados a la formación de tumores hipofisarios incrementó a lo largo de las últimas décadas, y se reconocen nuevas vías de desarrollo neoplásico. Sin embargo, en la actualidad existen pocos enfoques terapéuticos para actuar específicamente sobre la vía de génesis tumoral subyacente identificada en cada caso.
Subject(s)
Adenoma , Pituitary Neoplasms , Carcinogenesis/genetics , Humans , Mutation , Pituitary Neoplasms/geneticsABSTRACT
Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-ß1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-ß1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFßR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-ß1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-ß1, as well as by SSTR2 overexpression. The OCT/TGF-ß1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-ß1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-ß1/TGFßR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Cell Proliferation/drug effects , Octreotide/pharmacology , Pituitary Neoplasms/drug therapy , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Somatotrophs/drug effects , Transforming Growth Factor beta1/pharmacology , Animals , Cell Line , Female , Humans , Mice, Nude , Phosphorylation , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Rats , Receptors, Somatostatin/genetics , Receptors, Somatostatin/metabolism , Signal Transduction , Somatotrophs/metabolism , Somatotrophs/pathology , Tumor Burden/drug effectsABSTRACT
BACKGROUND: PTP4A3 is a subclass of a protein tyrosine phosphatase super family and is expressed in a range of epithelial neoplasms. We evaluated PTP4A3 expression and its association with clinicopathological parameters in different types of functioning pituitary adenomas. METHODS: A total of 34 functioning pituitary adenomas samples were evaluated in this observational study. PTP4A3 expression was examined by immunohistochemical staining, and, possible correlations between PTP4A3 and some clinicopathological variables were investigated. RESULTS: PTP4A3 was expressed in 19 out of 34 tumours (55%), at the cytoplasmic level of tumorous cells. Moreover, there was significant association (p=0.042) between PTP4A3 expression and tumorous size. CONCLUSIONS: PTP4A3 was expressed in more than half of the tumours analysed, with there being a significant association with the tumorous size of functioning adenomas. This allows to speculate that PTP4A3 may regulate tumour growth, although further investigations are necessary to determine if this phosphatase can serve as a biomarker or used as a therapeutic target in pituitary macroadenomas.
Subject(s)
Adenoma/diagnosis , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/metabolism , Pituitary Neoplasms/diagnostic imaging , Protein Tyrosine Phosphatases/metabolism , Adenoma/metabolism , Adenoma/pathology , Adult , Cytoplasm/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/genetics , Pituitary Gland/metabolism , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Protein Tyrosine Phosphatases/genetics , Retrospective Studies , Young AdultABSTRACT
Introduction: Acromegaly prevalence is 35-70 / million. Transsphenoidal surgery is the first-line treatment, with a remission rate of 80% for microadenomas and 50% for macroadenomas. Our aim was to evaluate the surgical results in Córdoba and determine predictive remission factors due to the lack of records. Methods: Retrospective-descriptive study of patients with surgery as the first therapeutic line. Remission criteria: IGF1 normalization for age/sex, with GH ≤1.0 g/L. Test X2 and Fisher's exact test with p<0.05. Results: 38 patients were included: 61% women and 39% men; Average age 45 years. Most frequent chief complaint: headache and acral growth (26%), visual disturbances (20%). Macroadenomas were the 84% of the tumors. Of 37 patients, 54% underwent microscopic surgery, 38% endoscopic and 8% transcranial. The 29% of patients showed post-operative complications and diabetes insipidus was the most frequent (10%). The percentage of them was: 33% transcranial surgery, 29% endoscopic and 25% microscopic (p = 0.557). The biochemical remission at 6 months was 34% and at 12 months 55% (p= 0.0001). No significant differences between the endoscopic and microscopic approach (p = 0.071). Of 36 patients, 31% showed complete tumor resection. The subjective clinical improvement was 88%. There weren´t predictive remission factors with significant differences. Conclusion: The surgical biochemical remission was similar to the bibliography. We didn´t find predictive remission factors but a larger number of patients could modify these results.
Introducción: La acromegalia tiene una prevalencia de 35-70/millón. La cirugía transesfenoidal es el tratamiento de elección, siendo la tasa de remisión del 80% en microadenomas y 50% en macroadenomas. Debido a la falta de registros, nos propusimos evaluar los resultados quirúrgicos en Córdoba y determinar factores predictivos de remisión. Métodos: Estudio retrospectivo-descriptivo de pacientes con cirugía como primera línea terapéutica. Criterios de remisión: normalización de IGF1 para edad/sexo, con GH ≤1,0 g/L.Test X2 y test exacto de Fisher y p<0,05. Resultados: Se incluyeron 38 pacientes: 61% mujeres y 39% hombres; edad promedio 45 años. Motivos de consulta más frecuentes: cefalea y crecimiento acral (26%), alteraciones visuales (20%). El 84% de los tumores fueron macroadenomas. De 37 pacientes, 54% se sometieron a cirugía microscópica, 38% endoscópica y 8% transcraneal. El 29% evidenció complicaciones postquirúrgicas, siendo la diabetes insípida la más frecuente (10%). El porcentaje de las mismas fue: cirugía transcraneal el 33%, endoscópica 29% y microscópica 25% (p= 0,557). La remisión bioquímica a los 6 meses fue de 34% y a los 12 meses 55% (p=0,0001). Sin diferencias significativas entre la vía endoscópica y microscópica (p=0,071). De 36 pacientes el 31% evidenció resección tumoral completa. La mejoría clínica subjetiva fue del 88%. No hubo factores predictivos de remisión bioquímica estadísticamente significativos. Conclusión: La remisión bioquímica con la cirugía fue similar a la bibliografía. No encontramos factores predictivos de remisión pero un número mayor de casos podría modificar estos resultados.
Subject(s)
Acromegaly , Acromegaly/surgery , Adenoma/surgery , Female , Growth Hormone-Secreting Pituitary Adenoma , Humans , Male , Middle Aged , Pituitary Neoplasms/surgery , Retrospective Studies , Sphenoid Bone , Treatment OutcomeABSTRACT
OBJECTIVE: An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values. DESIGN: A retrospective study in a single tertiary care hospital was performed. PATIENTS: A total of 1981 pregnant women were studied during 2012. MEASUREMENTS: Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters. RESULTS: Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed. CONCLUSIONS: There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.
Subject(s)
Thyrotropin/blood , Abortion, Spontaneous/blood , Adult , Female , Humans , Hypothyroidism/blood , Pregnancy , Pregnancy Complications , Pregnancy Outcome , Pregnancy Trimester, First , Retrospective Studies , Thyroid Function TestsABSTRACT
INTRODUCTION: Pituitary tumors comprise a quarter of the intracranial neoplasms and the adenomas represent the highest percentage of them. They are benign, but they can be invasive and they have an impact in morbidity and mortality. OBJECTIVE: To analyze the clinical features of pituitary adenomas tumors, and create a computerized registry to improve strategies for diagnosis and monitoring of these patients. METHODS: A retrospective, descriptive analysis of 102 medical records of a total of 191 patients who attended the endocrinology service from 2003 to 2014 .The variables were analyzed by the corresponding descriptive statistics. The SPSS 11.5 was used. RESULTS: 63% were women, and (74.4%) had age from 25-60 years. 54% were nonfunctioning adenomas, 28% to prolactinomas, 11.8% and 6.2% somatotropinomas corticotropinomas. In all types the female group was predominant, except nonfunctioning. Of the nonfunctioning adenomas 79% were macroadenomas, prolactinomas 52% were microadenomas and surgery was performed in 37% of them. The somatotropinomas, 80% were macroadenomas, 80% of patients and 40% radiotherapy was operated. In corticotropinomas, both micro and macroadenomas were submitted by the same percentage (50%) and all of them underwent surgery. CONCLUSION: The findings are consistent with the literature in terms of frequency and age of onset of adenomas. We suggest the development of a registry to optimize the monitoring and treatment of patients, research and scientific publication.
Introducción: Los tumores hipofisarios comprenden la cuarta parte de las neoplasias intracraneales y los adenomas son el mayor porcentaje de ellos. Son de naturaleza benigna, pero pueden ser invasivos y producir impacto en la morbi-mortalidad. Objetivo: analizar las características clínicas de los pacientes con diagnóstico de adenomas hipofisarios y crear un registro computarizado para mejorar las estrategias de diagnóstico y seguimiento de estos pacientes. Metodología: Se realizó un análisis retrospectivo, descriptivo, de 102 historias clínicas sobre un total de 191 pacientes que concurrieron al servicio de endocrinología desde el año 2003 al 2014 . Las variables fueron analizadas mediante las correspondientes estadísticas descriptivas. Se utilizó el programa SPSS 11.5. Resultados: El 63% fueron mujeres, y el mayor porcentaje etario entre 25-60 años (74.4%). El 54% correspondió a adenomas no funcionantes, el 28% a prolactinomas, el 11.8% somatotropinomas y el 6.2% corticotropinomas. En todos los tipos el grupo femenino fue mayoritario, excepto en los no funcionantes. De los adenomas no funcionantes el 79% fueron macroadenomas, los prolactinomas el 52% fueron microadenomas y se realizó cirugía en el 37% de ellos. Los somatotropinomas, en el 80% fueron macroadenomas, se operó el 80% de los pacientes y radioterapia al 40%. En los corticotropinomas, tanto micro como macroadenomas se presentaron en igual porcentaje (50%) y todos ellos recibieron tratamiento quirúrgico. Conclusión: Los hallazgos coinciden con la literatura en cuanto a frecuencia y edad de presentación de los adenomas. Consideramos valioso la elaboración de un registro que nos permita optimizar el seguimiento y tratamiento de los pacientes, la investigación y divulgación científica.
Subject(s)
Adenoma/classification , Pituitary Neoplasms/classification , Adenoma/pathology , Adenoma/therapy , Adult , Female , Humans , Male , Middle Aged , Neoplasm Grading , Pituitary Neoplasms/pathology , Pituitary Neoplasms/therapy , Retrospective Studies , Socioeconomic Factors , Treatment OutcomeABSTRACT
UNLABELLED: The prolactinomas are the most common functioning pituitary tumors. The hyperprolactinemia is associated with anovulation and infertility. OBJECTIVES: a) describe the relationship between hyperprolactinemia and fertility, b) review the results of the use of dopamine agonists during pregnancy and embryo-fetal development and c) review the therapeutic management in micro and macroprolactinomas during pregnancy. CONTENT: Medical therapy with dopamine agonists is the best treatment for prolactinomas of any size or invasiveness and restores ovulatory cycles in 80-90 % of patients. Cabergoline currently suggested rather than bromocriptine due to their excellent tolerability and long half-life. In general, it is recommended that fetal exposure to all drugs be limited to as short a period as possible. In the absence of menstrual period, the drug should be discontinued and confirm pregnancy. CONCLUSION: Both, bromocriptine and cabergoline, showed no evidence of obstetric and neonatal complications; however, experience with bromocriptine is higher. The patients with macroprolactinomas should be monitored clinically and evaluate the symptoms related to increased tumor size. If growth in the adenoma is suspected, nuclear magnetic resonance and neuro-ophthalmologic examination should be performed. In microprolactinomas the ophthalmologic examination is no formal indication. There is evidence that breastfeeding no increased risk for tumor growth.
Los prolactinomas son los tumores hipofisarios funcionantes más comunes. La hiperprolactinemia que generan se asocia con anovulación e infertilidad. OBJETIVOS: a) describir la relación entre hiperprolactinemia y fertilidad, b) revisar los resultados del uso de agonistas dopaminérgicos durante el embarazo y el desarrollo embriofetal y c) actualizar el manejo terapéutiterapéutico en micro y macroprolactinomas durante la gestación. CONTENIDO: Los agonistas dopaminérgicos son el tratamiento de primera línea para prolactinomas de cualquier tamaño o grado de invasión y restauran los ciclos ovulatorios en el 80 a 90 % de las pacientes. La cabergolina se sugiere actualmente en lugar de bromocriptina, debido a su excelente tolerabilidad y prolongada vida media. Se aconseja que la exposición fetal a todos los medicamentos sea lo más limitada posible. Ante la ausencia del período menstrual debe suspenderse el fármaco y confirmar el embarazo. CONCLUSION: Tanto bromocriptina como cabergolina no mostraron evidencia de complicaciones obstétricas ni neonatales, sin embargo, la experiencia con bromocriptina es mayor. Las pacientes con macroprolactinomas deben ser controladas clínicamente y evaluar sintomatología relacionada con el aumento del tamaño tumoral. Si se sospecha crecimiento del adenoma, debe solicitarse resonancia magnética nuclear y examen neuro-oftalmológico. En microprolactinomas la campimetría no es una indicación formal. Hay evidencia de que la lactancia materna no presenta mayor riesgo para el crecimiento tumoral.
