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1.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(1): 53-60, ene. 2020. tab
Artigo em Espanhol | IBECS-Express | ID: ibc-ET2-3642

RESUMO

La insuficiencia suprarrenal aguda (ISA) es una urgencia médica potencialmente letal cuya prevención y tratamiento deberían ser conocidos por todos los profesionales médicos. La ISA es una condición infradiagnosticada debido a la inespecificidad de los síntomas de presentación, pero su diagnóstico y tratamiento con glucocorticoides es vital. Puede ser desencadenada por una deficiencia de novo en la síntesis de cortisol o secundaria a la omisión del tratamiento hormonal sustitutivo con corticoides o al ajuste inadecuado de la dosis requerida en situaciones de estrés en el paciente ya diagnosticado. La prevención de la ISA disminuye de forma significativa la mortalidad cardiovascular y por infecciones de los pacientes con insuficiencia renal y mejora su calidad de vida. Por ello, es fundamental la adecuada educación del paciente, sus familiares y del personal sanitario. El Grupo de Trabajo de Patología Suprarrenal del Área de Conocimiento de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición (SEEN) ha elaborado, a partir de una propuesta de la Junta Directiva de la SEEN, esta guía para el óptimo manejo de la insuficiencia suprarrenal en fase aguda. Esta guía tiene el objetivo de ser eminentemente práctica y dar recomendaciones orientadas a todos los profesionales sanitarios que pueden estar involucrados en el diagnóstico, tratamiento y la prevención de la ISA. Así mismo, pretende facilitar pautas de actuación para el paciente y sus familiares en su manejo y prevención


Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention

2.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31926931

RESUMO

INTRODUCTION: Thyroid nodule (TN) is a common reason for consultation in daily practice. The purpose of this study was to evaluate the diagnosis and treatment of TNs in our environment and to assess the current status regarding the existence and structure of high-resolution TN clinics. MATERIAL AND METHODS: Members of the Spanish Society of Endocrinology and Nutrition were invited in 2018 to participate in an online survey on the diagnostic and therapeutic processes of TN. RESULTS: A total of 211 valid surveys were received. Of all respondents, 30.8% stated that there were high-resolution TN clinics in their environment, with the endocrinologist being the main person responsible for performing ultrasonography (87.7%) and fine needle aspiration (FNA) (69.2%). For ultrasound classification of TNs, 32.7% used the ATA criteria, 32.2% the TI-RADS criteria, and 22.7% no classification. In situ verification of sample suitability was performed in 35.5% of the cases, and molecular analysis in 8.1%. With regard to clinical discharge, 65.4% would consider it after 5 years of follow-up and with a benign FNA. In the event of a Bethesda III result, 50.2% of respondents would repeat FNA and 35.5% would opt for surgery; if a Bethesda IV result was found, 95.8% would opt for surgery. CONCLUSIONS: High-resolution TN clinics are structures increasingly implemented in our environment where the endocrinologist is the main person responsible for performing ultrasonography and FNA. The standard clinical practice in our specialty is consistent with most recommendations concerning clinical practice guidelines for TNs.

3.
Endocrinol Diabetes Nutr ; 67(1): 53-60, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31003863

RESUMO

Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention.

4.
Int J Cancer ; 146(2): 521-530, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31403184

RESUMO

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

5.
Pituitary ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823249

RESUMO

AIM: The ACROPRAXIS program aims to describe the management of acromegaly in Spain and provide guidance. METHODS: Ninety-three endocrinologists were organized into 13 panels to discuss the practical issues in managing acromegaly. Based on the key learnings, an online Delphi survey with 62 statements was performed, so those statements achieving consensus could be used as guidance. Statements were rated on a 9-point scale (9, full agreement; consensus > 66.6% of response in the same tertile). RESULTS: Ninety-two endocrinologists (98.8%) answered two rounds of the survey (mean age 47.6 years; 59.8% women; median 18.5 years of experience). Consensus was achieved for 49 (79%) statements. DIAGNOSIS: The levels of insulin-like growth factor I (IGFI) is the preferred screening test. If IGFI levels 1-1.3 ULN, the test is repeated and growth hormone (GH) after oral glucose tolerance test (OGTT) is assessed. A pituitary magnetic resonance is performed after biochemical diagnosis. TREATMENT: Surgery is the first treatment choice for patients with microadenoma or macroadenoma with/without optical pathway compression. Pre-surgical somatostatin analogues (SSA) are indicated when surgery is delayed and/or to reduce anaesthesia-associated risks. After unsuccessful surgery, reintervention is performed if the residual tumor is resectable, while if non-resectable, SSA are administered. Follow-up First biochemical and clinical controls are performed 1-3 months after surgery. Disease remission is considered if random GH levels are < 1 µg/L or OGTT is < 1 or ≤ 0.4 µg/L, depending on the assay's sensitivity. CONCLUSION: Current clinical management for acromegaly is homogeneous across Spain and generally follows clinical guidelines.

7.
Acta otorrinolaringol. esp ; 70(5): 301-305, sept.-oct. 2019. graf, tab
Artigo em Espanhol | IBECS-Express | ID: ibc-FGT-2493

RESUMO

El hipoparatiroidismo es la complicación más frecuente tras la tiroidectomía total. Se define por la presencia de hipocalcemia con unos niveles de hormona paratiroidea (PTH) bajos o inadecuadamente normales. La hipocalcemia aguda es una complicación potencialmente grave. Su tratamiento se basa, según la gravedad del cuadro, en la administración de calcio por vía oral o intravenosa, pudiendo requerir asimismo calcitriol oral. El riesgo de hipocalcemia sintomática tras una tiroidectomía es muy bajo si la PTH postoperatoria desciende menos del 80% respecto de la preoperatoria. Estos pacientes podrían ser dados de alta sin tratamiento, aunque los umbrales son variables entre laboratorios y recomendamos extremar la vigilancia en los casos de riesgo aumentado (enfermedad de Graves, grandes bocios, reintervenciones o constancia de la extirpación de alguna paratiroides). El tratamiento a largo plazo busca controlar los síntomas manteniendo la calcemia en el límite bajo de la normalidad, vigilando el producto calcio-fósforo y la aparición de hipercalciuria


Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria

8.
Endocr Connect ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557724

RESUMO

Primary hyperparathyroidism is the most frequent manifestation of Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long-term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). 89 patients (49 men and 40 women, 34.2 + 13 years old) were included. 64 out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs. 7/12, p<0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.

9.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(7): 459-463, ago.-sept. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182865

RESUMO

El hipoparatiroidismo es la complicación más frecuente tras la tiroidectomía total. Se define por la presencia de hipocalcemia con unos niveles de hormona paratiroidea (PTH) bajos o inadecuadamente normales. La hipocalcemia aguda es una complicación potencialmente grave. Su tratamiento se basa, según la gravedad del cuadro, en la administración de calcio por vía oral o intravenosa, pudiendo requerir asimismo calcitriol oral. El riesgo de hipocalcemia sintomática tras una tiroidectomía es muy bajo si la PTH postoperatoria desciende menos del 80% respecto de la preoperatoria. Estos pacientes podrían ser dados de alta sin tratamiento, aunque los umbrales son variables entre laboratorios y recomendamos extremar la vigilancia en los casos de riesgo aumentado (enfermedad de Graves, grandes bocios, reintervenciones o constancia de la extirpación de alguna paratiroides). El tratamiento a largo plazo busca controlar los síntomas manteniendo la calcemia en el límite bajo de la normalidad, vigilando el producto calcio-fósforo y la aparición de hipercalciuria


Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria


Assuntos
Humanos , Consenso , Hipoparatireoidismo/complicações , Hipoparatireoidismo/epidemiologia , Tireoidectomia/métodos , Tireoidectomia/efeitos adversos , Cálcio/administração & dosagem , Cuidados Pré-Operatórios/métodos , Liberação de Cirurgia/normas
10.
Theranostics ; 9(17): 4946-4958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410193

RESUMO

Rationale: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients' liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients' management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitors.

11.
Acta Otorrinolaringol Esp ; 70(5): 301-305, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31387688

RESUMO

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.

12.
Endocrine ; 66(2): 405-415, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31317524

RESUMO

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

13.
Endocrinol Diabetes Nutr ; 66(7): 459-463, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31182347

RESUMO

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.

14.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(5): 320-329, mayo 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-182807

RESUMO

Objectives: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline(R) Autogel(R)). Methods: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. Results: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. Conclusions: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals


Objetivos: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline(R) Autogel(R)) utilizados en la práctica clínica. Métodos: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH <2,5ng/ml y/o IGF-I normalizado en ≥2 evaluaciones). El objetivo principal fue determinar el período de tiempo desde el inicio del tratamiento con lanreótida hasta la normalización hormonal. Resultados: La mediana de edad de los pacientes fue 64 años, 21 pacientes eran hombres, 39 pacientes habían recibido cirugía, 14 pacientes habían recibido radioterapia. Los valores hormonales medianos al inicio del tratamiento con lanreótida fueron GH: 2,6ng/ml, IGF-I: 1,6×LSN. La dosis inicial más frecuente de lanreótida fue de 120mg (29 pacientes). Los principales regímenes iniciales fueron 60mg/4 semanas (n=13), 90mg/4 semanas (n=6), 120mg/4 semanas (n=13), 120mg/6 semanas (n=6), 120mg/8 semanas (n=9). Se administró un régimen de intervalo prolongado (≥6 semanas) en 25 pacientes. La duración media del tratamiento con lanreótida fue de 68 meses (7-205). El tiempo medio hasta lograr el control hormonal fue de 4,9 meses. Las inyecciones se manejaron sin asistencia médica en 13 pacientes. La mediana del número de visitas al endocrinólogo hasta el control hormonal fue 3. Cincuenta y un pacientes estaban "satisfechos"/"muy satisfechos" con el tratamiento y 49 pacientes no olvidaron ninguna dosis. Conclusiones: El tratamiento en la vida real con lanreótida Autogel condujo a un control hormonal temprano en pacientes que respondieron, con una alta adherencia al tratamiento y satisfacción con el tratamiento, a pesar de la disparidad de las dosis iniciales y los intervalos de dosificación


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Acromegalia/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Hormônio do Crescimento Humano/metabolismo , Somatostatina/análogos & derivados , Acromegalia/sangue , Estudos Retrospectivos , Peptídeos Cíclicos/administração & dosagem , Acromegalia/metabolismo , Cooperação e Adesão ao Tratamento , Somatostatina/administração & dosagem
15.
EBioMedicine ; 43: 537-552, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30975543

RESUMO

BACKGROUND: Acromegaly is produced by excess growth hormone secreted by a pituitary adenoma of somatotroph cells (ACRO). First-line therapy, surgery and adjuvant therapy with somatostatin analogs, fails in 25% of patients. There is no predictive factor of resistance to therapy. New therapies are investigated using few dispersed tumor cells in acute primary cultures in standard conditions where the cells do not grow, or using rat pituitary cell lines that do not maintain the full somatotroph phenotype. The RET/PIT1/p14ARF/p53 pathway regulates apoptosis in normal pituitary somatotrophs whereas the RET/GDNF pathway regulates survival, controlling PIT1 levels and blocking p14ARF (ARF) and p53 expression. METHODS: We investigated these two RET pathways in a prospective series of 32 ACRO and 63 non-functioning pituitary adenomas (NFPA), studying quantitative RNA and protein gene expression for molecular-clinical correlations and how the RET pathway might be implicated in therapeutic success. Clinical data was collected during post-surgical follow-up. We also established new'humanized' pituitary cultures, allowing 20 repeated passages and maintaining the pituitary secretory phenotype, and tested five multikinase inhibitors (TKI: Vandetanib, Lenvatinib, Sunitinib, Cabozantinib and Sorafenib) potentially able to act on the GDNF-induced RET dimerization/survival pathway. Antibody arrays investigated intracellular molecular pathways. FINDINGS: In ACRO, there was specific enrichment of all genes in both RET pathways, especially GDNF. ARF and GFRA4 gene expression were found to be opposing predictors of response to first-line therapy. ARF cut-off levels, calculated categorizing by GNAS mutation, were predictive of good response (above) or resistance (below) to therapy months later. Sorafenib, through AMPK, blocked the GDNF/AKT survival action without altering the RET apoptotic pathway. INTERPRETATION: Tumor ARF mRNA expression measured at the time of the surgery is a prognosis factor in acromegaly. The RET inhibitor, Sorafenib, is proposed as a potential treatment for resistant ACRO. FUND: This project was supported by national grants from Agencia Estatal de Investigación (AEI) and Instituto Investigación Carlos III, with participation of European FEDER funds, to IB (PI150056) and CVA (BFU2016-76973-R). It was also supported initially by a grant from the Investigator Initiated Research (IIR) Program (WI177773) and by a non-restricted Research Grant from Pfizer Foundation to IB. Some of the pituitary acromegaly samples were collected in the framework of the Spanish National Registry of Acromegaly (REMAH), partially supported by an unrestricted grant from Novartis to the Spanish Endocrine Association (SEEN). CVA is also supported from a grant of Medical Research Council UK MR/M018539/1.


Assuntos
Acromegalia/diagnóstico , Acromegalia/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Fator de Transcrição Pit-1/metabolismo , Proteína Supressora de Tumor p14ARF/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Acromegalia/genética , Acromegalia/terapia , Animais , Apoptose/genética , Biomarcadores , Terapia Combinada , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Humanos , Imuno-Histoquímica , Modelos Biológicos , Mutação , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-ret/genética , Ratos , Transdução de Sinais , Fator de Transcrição Pit-1/genética , Resultado do Tratamento , Proteína Supressora de Tumor p14ARF/genética , Proteína Supressora de Tumor p53/genética
16.
Endocrinol Diabetes Nutr ; 66(5): 320-329, 2019 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30773338

RESUMO

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.


Assuntos
Acromegalia/sangue , Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Peptídeos Cíclicos/administração & dosagem , Somatostatina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Géis , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Somatostatina/administração & dosagem , Fatores de Tempo , Adulto Jovem
17.
J Ultrasound Med ; 38(10): 2565-2571, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30693978

RESUMO

OBJECTIVES: We aimed to compare the effectiveness of contrast-enhanced ultrasound (CEUS), technetium Tc 99m methoxyisobutylisonitrile (99m Tc-MIBI) single-photon emission computed tomographic (SPECT) scintigraphy, and high-resolution ultrasound (US) in the detection of a pathologic parathyroid gland in patients with primary hyperparathyroidism (pHPT). METHODS: Twenty-nine consecutive patients with pHPT were prospectively enrolled and underwent preoperative imaging with 99m Tc-MIBI SPECT scintigraphy, high-resolution US, and CEUS and subsequent parathyroidectomy. Contrast-enhanced US examinations were performed by an experienced examiner who was blinded to the results of scintigraphy and high-resolution US. The diagnostic performance of all of the imaging tests was analyzed in comparison with the pathologic anatomic findings. All investigations were performed at La Paz University Hospital. RESULTS: In the 29 patients (22 female and 7 male), a total of 31 parathyroid adenomas were detected: single lesions in 27 patients and a double lesion in 2 patients. Contrast-enhanced US revealed sensitivity of 66.7% (95% confidence interval [CI], 46%-82.7%) for detection of single adenomas in comparison with 77.8 % (95% CI, 57.3%-90.6) for 99m Tc-MIBI SPECT scintigraphy and 51.8% (95% CI, 32.3%-70.8%) for high-resolution US (P = .100). With CEUS, double adenomas could be detected in both cases (sensitivity, 100%); however, scintigraphy and high-resolution US did not detect any cases of double adenomas. In addition, CEUS allowed the differentiation of lymphatic nodes from parathyroid glands in 2 patients. No side effects were observed for CEUS. CONCLUSIONS: In our study, CEUS facilitated the detection and diagnosis of double adenomas compared with high-resolution US and 99m Tc-MIBI SPECT scintigraphy. Additionally, CEUS was useful in the differentiation between parathyroid adenomas and lymph nodes.

18.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(5): 297-305, mayo 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-176040

RESUMO

La acromegalia es una enfermedad rara, con abundantes comorbilidades que deterioran la calidad de vida y limitan la supervivencia. Existen discrepancias en diversas guías clínicas respecto al diagnóstico y los criterios de control poscirugía, así como para el cribado y el manejo óptimo de las comorbilidades. El objetivo de este consenso de expertos ha sido establecer recomendaciones específicas para nuestro ámbito asistencial español. Hemos revisado las recomendaciones existentes, la evidencia científica que las sustentan y las principales controversias. Desafortunadamente, la baja prevalencia y la elevada variabilidad clínica de la acromegalia no permiten disponer de evidencias científicas sólidas. Para atenuar este inconveniente hemos utilizado un cuestionario Delphi modificado, que combina la mejor evidencia científica disponible con el juicio colectivo de expertos. Tras un debate presencial se generó el cuestionario que fue respondido por un grupo de 17 endocrinólogos españoles expertos en acromegalia. Se consiguió un alto grado de consenso (79,3%), aceptando 65 de un total de 82 aseveraciones planteadas. De esta manera, se han perfilado algunos criterios diagnósticos y de control poscirugía. Respecto a las comorbilidades, se han establecido o precisado recomendaciones para el cribado y el manejo de las enfermedades oncológica, cardiovascular, respiratoria (apnea del sueño), metabólica (dislipidemia y diabetes), osteoarticular e hipopituitarismo. Las recomendaciones consensuadas pueden facilitar y homogeneizar la asistencia clínica a los pacientes con acromegalia de nuestro sistema sanitario español


Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system


Assuntos
Humanos , Acromegalia/diagnóstico , Programas de Rastreamento/métodos , Acromegalia/cirurgia , Comorbidade , Inquéritos e Questionários , Doenças Cardiovasculares , Neoplasias Colorretais , Nódulo da Glândula Tireoide , Síndromes da Apneia do Sono , Artropatias , Diabetes Mellitus , Hipertensão
19.
Endocrinol Diabetes Nutr ; 65(5): 297-305, 2018 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29653911

RESUMO

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system.


Assuntos
Acromegalia/diagnóstico , Acromegalia/cirurgia , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Absorciometria de Fóton , Acromegalia/complicações , Acromegalia/tratamento farmacológico , Adenoma/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Pólipos do Colo/diagnóstico , Pólipos do Colo/etiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Técnicas de Diagnóstico Cardiovascular , Fraturas Espontâneas/diagnóstico , Fraturas Espontâneas/etiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Humanos , Hipofisectomia , Polissonografia , Cuidados Pós-Operatórios , Guias de Prática Clínica como Assunto , Síndromes da Apneia do Sono/diagnóstico
20.
PLoS One ; 12(9): e0183539, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28898247

RESUMO

Acromegaly is a rare disease with nonspecific symptoms with acral enlargement being almost universally present at diagnosis. The estimated prevalence is 40-125 cases/million but targeted universal screening studies have found a higher prevalence (about 10 fold). The aim of the ACROSAHS study was to investigate the prevalence of acromegaly and acromegaly comorbidities in patients with sleep apnea symptoms and acral enlargement. ACROSAHS was a Spanish prospective non-interventional epidemiological study in 13 Hospital sleep referral units. Facial and acral enlargement symptoms including: ring size and shoe size increase, tongue, lips and jaws enlargement, paresthesia or carpal tunnel syndrome and widening of tooth spaces, as well as other typical acromegaly comorbidities were recorded with a self-administered questionnaire of patients who attended a first visit for sleep apnea symptoms between 09/2013 and 07/2014. Serum insulin-like growth factor type 1 (IGF1) was measured in patients with ≥1 acral symptom to determine the prevalence of acromegaly. Of the 1557 patients enrolled, 1477 with complete data (72% male) were analyzed. 530 patients (36%) reported at least 1 acral enlargement symptom and were tested for IGF-1, 41 were above range, persisted in 7, and among those, 2 cases of acromegaly were diagnosed (prevalence of at least 1.35 cases/1000). Overall, 1019 patients (69%) had ≥2 acromegaly symptoms and should have been screened according to guidelines; moreover 373 patients (25%) had ≥1 symptom of acral enlargement plus ≥3 other acromegaly symptoms. In conclusion, in patients with sleep apnea symptoms and acral enlargement, we found an acromegaly prevalence of at least 1.35 cases per 1000 and a high prevalence of typical acromegaly symptoms. It is important that sleep specialists are aware of acromegaly symptoms to aid with acromegaly diagnosis.


Assuntos
Acromegalia/epidemiologia , Acromegalia/etiologia , Síndromes da Apneia do Sono/complicações , Acromegalia/metabolismo , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prevalência , Síndromes da Apneia do Sono/diagnóstico , Espanha/epidemiologia
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