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1.
Endocr Relat Cancer ; 27(6): 375-389, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32302973

RESUMO

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.

2.
Cancers (Basel) ; 11(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835737

RESUMO

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

3.
Foods ; 8(10)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627283

RESUMO

Grapefruit is a fruit with interesting nutritional value and functional properties, but a short life. Freeze-drying (FD) is a valuable technique as it produces high-quality dehydrated products. This study is aimed to obtain new food ingredients based on freeze-dried grapefruit formulated with high molecular weight solutes (gum arabic and bamboo fiber) in three different proportions (F1, F2, and F3). To improve the FD, a mild microwave drying pre-treatment was applied. Influence of the water content and the presence of high molecular weight solutes on freeze-drying kinetics was tested by Midilli-Kucuk and Page models. The best FD kinetic model fit on grapefruit powders were Midilli-Kucuk for F2 and F3, and Page for F1, and the adequate freeze-drying times for F1, F2, and F3 were 24, 16, and 18 h, respectively. Final samples were evaluated for nutritional and antioxidant capacity. Gum arabic and bamboo fiber present a protector effect, which results in a significant antioxidant capacity due to the protection of flavonoids and antioxidant vitamins. These novel food ingredients could be of great interest for the food industry in order to develop foods with improved antioxidant capacity as well as enriched in natural fibers and/or micronutrients.

4.
Pituitary ; 22(2): 137-145, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30756345

RESUMO

PURPOSE: The burden of chronic daily subcutaneous administration of pegvisomant on adherence has not been previously studied. This study was aimed to determine the adherence to pegvisomant treatment in acromegaly patients in the real-world clinical practice setting in Spain. METHODS: Multicenter, observational, descriptive, cross-sectional study in patients with acromegaly treated with pegvisomant for at least 12 months. Patient adherence was indirectly determined by Batalla and Haynes-Sackett questionnaires and directly by prescription record review. Additionally, treatment satisfaction was assessed by the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) and treatment convenience by an ad-hoc Pegvisomant questionnaire. Errors in reconstitution and administration process were determined by direct observation. RESULTS: 108 patients were included in the analysis. Rates of adherence varied from 60.7 to 92.1% and did not correlate with disease control. Older patient age and alternative schedules other than daily pegvisomant dosing were associated with lower adherence. Treatment satisfaction and convenience was high, with a mean (SD) total SATMED-Q score of 74.6 ± 15.4 over 100 and a total ad-hoc Pegvisomant questionnaire score of 71.2 ± 15.2 over 100. 34.3% of patients made mistakes during the reconstitution /administration process. CONCLUSIONS: Patient adherence to pegvisomant was high (60.7-92.1%), but more than a third of the patients in the study made mistakes during the administration process, with a potential impact on disease control. Besides dosing compliance, correct administration of medication should be carefully assessed in these patients.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Adulto , Idoso , Estudos Transversais , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Espanha , Inquéritos e Questionários
5.
Minerva Endocrinol ; 44(2): 137-142, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30531696

RESUMO

Silent somatotroph pituitary neuroendocrine tumors (or silent growth hormone pituitary neuroendocrine tumors, SGH-PitNET) are neoplasias with positive immunostaining for growth hormone (GH), in patients with no signs and symptoms of acromegaly nor biochemical evidence of GH hypersecretion. From a clinical stand-point they are considered and managed as non-functioning pituitary tumors, since they usually come to evidence due to mass-effects (headache, visual impairment, hypopituitarism) or as asymptomatic pituitary incidentalomas. SGH-PitNET have deserved little attention in the medical literature, and no specific guidelines exist regarding their management. However, identification of a particular tumor lineage through immunostaining patterns of non-functioning pituitary tumors may determine postoperative medical therapy in the near future. This review updates the current knowledge about the epidemiologic, clinical, pathological and molecular characteristics of this particular type of pituitary tumors.


Assuntos
Adenoma/terapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Adenoma/epidemiologia , Adenoma/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Humanos
6.
J Clin Endocrinol Metab ; 104(4): 1272-1282, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423170

RESUMO

CONTEXT: Epigenetic alterations may play a role in the development and behavior of pituitary neuroendocrine tumors (PitNETs). OBJECTIVE: To evaluate the effect of methylation of tumor suppressor genes (TSGs) on their gene expression and on the behavior of PitNETs. MATERIAL AND METHODS: We used methylation-specific multiplex ligation-dependent probe amplification and quantitative real-time PCR techniques to analyze the DNA-promoter hypermethylation and gene expression of 35 TSGs in 105 PitNETs. We defined functionality, size, and invasiveness of tumors according to their clinical manifestations, Hardy's classification, and MRI invasiveness of the cavernous sinus, respectively. RESULTS: We observed different methylation patterns among PitNET subtypes. The methylation status of TP73 correlated negatively with its gene expression in the overall series (P = 0.013) and in some subtypes. MSH6 and CADM1 showed higher methylation frequency in macroadenomas than in microadenomas in the overall series and in corticotroph PitNETs (all P ≤ 0.053). ESR1 and RASSF1 were more highly methylated in noninvasive than in invasive tumors in the overall series (P = 0.054 and P = 0.031, respectively) and in the gonadotroph subtype (P = 0.055 and P = 0.050, respectively). ESR1 and CASP8 appeared more hypermethylated in functioning than in silent corticotroph tumors (P = 0.034 and P = 0.034, respectively). CONCLUSIONS: DNA methylation of TSGs has a selective effect on their gene expression and on the growth and invasiveness of PitNETs. Its involvement in their functionality is biased because all silent operated tumors are macroadenomas, whereas all operated microadenomas are functioning ones. Therefore, the subtypes of PitNETs should be considered different entities.


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Tumores Neuroendócrinos/genética , Neoplasias Hipofisárias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Regulação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Tumores Neuroendócrinos/patologia , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Regiões Promotoras Genéticas/genética , Carga Tumoral/genética , Adulto Jovem
7.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(8): 428-437, oct. 2018.
Artigo em Espanhol | IBECS | ID: ibc-176283

RESUMO

Objetivos: Buscar consenso sobre cuestiones que pueden generar dudas en el manejo de la acromegalia en España. Método: Grupos nominales y Delphi. Se seleccionaron 4 expertos que definieron cuestiones relevantes en el manejo de la acromegalia sobre las que se formularon distintas aseveraciones y recomendaciones. Posteriormente, se eligió un grupo de 30 expertos adicionales con el que se determinó el grado de acuerdo con las mismas en 2 rondas Delphi. Se establecieron las siguientes categorías de respuesta: 1) totalmente en desacuerdo; 2) básicamente en desacuerdo; 3) básicamente de acuerdo; y 4) totalmente de acuerdo. Se definió acuerdo si, en la segunda ronda Delphi≥70% de las respuestas estaban en las categorías 1 y 2 (consenso con el desacuerdo) o 3 y 4 (consenso con el acuerdo). Resultados: Se generaron aseveraciones y recomendaciones sobre diversos aspectos de la práctica clínica incluyendo: 1) instrumentos de utilidad en la individualización del tratamiento (marcadores predictivos de respuesta, técnicas de imagen, etc.); 2) perfiles clínicos y comorbilidades en la individualización del tratamiento; 3) papel del paciente en la toma de decisiones terapéuticas; y 4) acceso al tratamiento (accesibilidad y equidad). La primera ronda Delphi incluyó 35 aseveraciones, en 6 se alcanzó consenso, 2 fueron eliminadas y 2 reformuladas. En la segunda se incluyeron 27 y se alcanzó consenso en 24 (22 en el acuerdo, 2 en el desacuerdo) y 3 se eliminaron. Conclusiones: Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones en el manejo de la acromegalia


Objectives: To seek a consensus on issues that may generate doubts in management of acromegaly in Spain. Method: Nominal groups and Delphi. Four experts defined relevant issues in management of acromegaly and generated different assertions and recommendations. Subsequently, a group of 30 additional experts was selected to test agreement with the assertions through two Delphi rounds. The following response categories were established: 1) Totally disagree; 2) Basically disagree; 3) Basically agree; 4) Totally agree. Agreement was defined as ≥70% of answers in categories 1 and 2 (consensus with the disagreement) or 3 and 4 (consensus with the agreement) in the second Delphi round. Results: Assertions covers various aspects of clinical practice, including: 1) Useful instruments in individualization of treatment (response predictive markers, imaging techniques, etc.); 2) Clinical profiles and relevant comorbidities in treatment individualization; 3) Role of patient in treatment decision-making; 4) Access to treatments (accessibility and equity). The first Delphi round included 35 assertions. Consensus was reached on six of these assertions, two were eliminated, and two were reformulated. Of the 27 assertions included in the second round, consensus was reached on 24 (22 in the agreement, two in the disagreement) and three were eliminated. Conclusions: This document is intended to solve some common clinical questions and to facilitate decision making in the management of patients with acromegaly


Assuntos
Humanos , Acromegalia/tratamento farmacológico , Tomada de Decisão Clínica , Somatostatina/uso terapêutico , Acromegalia/fisiopatologia , Biomarcadores , Comorbidade , Participação do Paciente , Pesquisa Qualitativa , Conferências de Consenso como Assunto
8.
Endocrinol Diabetes Nutr ; 65(8): 428-437, 2018 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30244765

RESUMO

OBJECTIVES: To seek a consensus on issues that may generate doubts in management of acromegaly in Spain. METHOD: Nominal groups and Delphi. Four experts defined relevant issues in management of acromegaly and generated different assertions and recommendations. Subsequently, a group of 30 additional experts was selected to test agreement with the assertions through two Delphi rounds. The following response categories were established: 1) Totally disagree; 2) Basically disagree; 3) Basically agree; 4) Totally agree. Agreement was defined as ≥70% of answers in categories 1 and 2 (consensus with the disagreement) or 3 and 4 (consensus with the agreement) in the second Delphi round. RESULTS: Assertions covers various aspects of clinical practice, including: 1) Useful instruments in individualization of treatment (response predictive markers, imaging techniques, etc.); 2) Clinical profiles and relevant comorbidities in treatment individualization; 3) Role of patient in treatment decision-making; 4) Access to treatments (accessibility and equity). The first Delphi round included 35 assertions. Consensus was reached on six of these assertions, two were eliminated, and two were reformulated. Of the 27 assertions included in the second round, consensus was reached on 24 (22 in the agreement, two in the disagreement) and three were eliminated. CONCLUSIONS: This document is intended to solve some common clinical questions and to facilitate decision making in the management of patients with acromegaly.


Assuntos
Acromegalia/terapia , Acromegalia/complicações , Técnica Delfos , Humanos , Guias de Prática Clínica como Assunto , Medicina de Precisão
9.
PLoS One ; 13(7): e0198877, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979686

RESUMO

The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.


Assuntos
Tumores Neuroendócrinos/diagnóstico , Hormônios Hipofisários/genética , Neoplasias Hipofisárias/diagnóstico , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Vasopressinas/genética , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Hipófise/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia
10.
PLoS One ; 12(7): e0180039, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28692683

RESUMO

AIM: The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. METHODS: Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. CONCLUSIONS: According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.


Assuntos
Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hormônios/genética , Hormônios/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Prevalência , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Reprodutibilidade dos Testes
11.
Obes Surg ; 26(8): 1836-42, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26661106

RESUMO

BACKGROUND: Specific data is needed to safely expand bariatric surgery and to preserve good surgical outcomes in response to the non-stop increase in obesity prevalence worldwide. OBJECTIVE: The aims of this study are to provide an overview of the baseline characteristics, type of surgery, and 30-day postoperative morbidity and mortality in patients undergoing bariatric surgery in Spanish public hospitals, and evaluate changes throughout the 2000-2014 period. MATERIAL AND METHODS: This is a descriptive study using data from the RICIBA, a computerized multicenter and multidisciplinary registry created by the Obesity Group of the Endocrinology and Nutrition Spanish Society. Three periods according to the date of surgery were created: January 2000 to December 2004 (G1), January 2005 to December 2009 (G2), and January 2010 to December 2014 (G3). RESULTS: Data from 3843 patients were available (44.8 ± 10.5 years, a 3:1 female-to-male ratio, 46.9 ± 8.2 kg/m(2)). Throughout the 15-year period assessed, candidate patients for bariatric surgery were progressively older and less obese, with an increase in associated comorbidities and in the prevalence of men. The global trend also showed a progressive decrease in Roux-en-Y gastric bypass, the most performed bariatric procedure (75.1 % in G1, 69.3 % in G2, and 42.6 % in G3; p < 0.001), associated with a parallel increase in sleeve gastrectomy (0.8 % in G1, 18.1 % in G2, and 39.6 % in G3; p < 0.001). An overall mortality rate of 0.3 % was reported. CONCLUSIONS: Data from Spain is similar to data observed worldwide. Information recorded in the National Registries like RICIBA is necessary in order to safely expand bariatric surgery in response to increasing demand.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/tendências , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/mortalidade , Período Pós-Operatório , Prevalência , Sistema de Registros , Espanha/epidemiologia
12.
Clin Hemorheol Microcirc ; 58(1): 1-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25339098

RESUMO

BACKGROUND: Subclinical hypothyroidism (SCH) has been suggested to be associated with increased cardiovascular risk by different mechanisms. Several cardiovascular risk factors have been analysed, but yielded controversial results. OBJECTIVES: We aimed to analyse whether there are differences in several cardiovascular risk markers, such as lipids, inflammatory parameters: plasma viscosity (PV), fibrinogen and C reactive protein (CRP); homocysteine (Hcy) and red blood cell distribution width (RDW), when comparing SCH and controls. We also analysed which of these parameters predict SCH risk and constitute independent markers. METHODS: We determined PV in a Fresenius capillary plasma viscosimeter, Hcy by a chemiluminiscent enzyme immunoassay, and biochemical and haematological parameters by conventional laboratory methods in 58 SCH outpatients and 58 controls matched for age and gender. RESULTS: SCH patients did not show statistical differences for glucose, lipids or leucocytes (p > 0.05). However, patients showed a higher prevalence for use of hypolipidaemic drugs, body mass index (BMI), thyroid stimulating hormone (TSH), PV, CRP, fibrinogen, Hcy and RDW (p < 0.05). RDW correlated with inflammation parameters: PV (r = 0.331, p < 0.05), fibrinogen (r = 0.424, p < 0.05), CRP (r = 0.433, p < 0.01) and leucocytes (r = 0.613, p < 0.01). None of the cardiovascular markers correlated with the TSH levels (p > 0.05) In the unadjusted logistic regression analyses, BMI ≥28 kg/m2, RDW ≥14%, Hcy ≥12 µm/L, fibrinogen ≥400 mg/dL and MCV ≤88 fL increased SCH risk, but only RDW ≥14% and fibrinogen ≥400 mg/dL independently increased this risk in the adjusted logistic regression analyses (OR = 4.68, 95% CI 1.20-18.30 P = 0.026; OR = 3.48, 95% CI 1.08-11.23 P = 0.037). CONCLUSION: SCH patients show a higher cardiovascular risk, characterised by increased PV, fibrinogen, Hcy and RDW. However, only fibrinogen ≥400 mg/dL and RDW ≥14% are independent predictors of SCH.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Adulto , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Eritrócitos/citologia , Feminino , Fibrinogênio/metabolismo , Voluntários Saudáveis , Homocisteína/sangue , Humanos , Técnicas Imunoenzimáticas , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Tireotropina/sangue , Viscosidade
15.
Rev. psiquiatr. salud ment ; 7(2): 88-95, abr.-jun. 2014. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-122172

RESUMO

Las alteraciones del funcionamiento de la glándula tiroidea influyen en la estabilidad afectiva repercutiendo negativamente en el curso clínico de la enfermedad bipolar. El principal estabilizador utilizado en este trastorno, las sales de litio, ejerce numerosos efectos sobre la fisiología del tiroides. La inhibición del recambio de la hormona tiroidea, que puede producirse con niveles terapéuticos de sales de litio, es el que tiene mayor relevancia clínica. Por otro lado, la disfunción tiroidea también parece ser más frecuente en pacientes bipolares no tratados con litio. Al margen de las numerosas complicaciones médicas y afectivas, también el sistema perceptivo o el cognitivo pueden verse afectados. De hecho, la presencia de una enfermedad tiroidea aumenta las tasas de trastorno obsesivo compulsivo, fobias, trastorno de pánico, trastorno depresivo mayor, ciclotimia o trastorno bipolar (TB). En casos de hipotiroidismo grave, la clínica puede ser semejante a una depresión melancólica o a una demencia. Por ello, en la práctica clínica diaria, es importante conocer bien los efectos de las sales de litio sobre la función tiroidea. En esta revisión abordaremos las principales disfunciones tiroideas presentes en los pacientes bipolares, generadas o no por el tratamiento con sales de litio, y aportaremos una serie de recomendaciones para su manejo clínico (AU)


Thyroid disfunction affects negatively emotional stability and worsens the clinical course of bipolar affective disorder. The main stabilizer used in this illness, lithium carbonate has numerous effects on the physiology of the thyroid, with the most significant being the inhibition of thyroid hormone release that may occur at therapeutic levels. These dysfunctions have also been reported most frequently in bipolar patients not undergoing treatment with lithium, and was not completely explained by the effects of this drug. Apart from the numerous medical complications and mood disturbances, the cognitive or perceptual system may also be affected. In fact, he presence of thyroid disease increases the rates of obsessive compulsive disorder, phobias, panic disorder, major depressive disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism, the clinical symptoms and signs can be similar to a melancholic depression or dementia. It is therefore important to know well all these possible complications in daily clinical practice. This review will cover the main thyroid dysfunctions present in bipolar patients, whether to not produced by treatment with lithium carbonate, and will provide a series of recommendations for clinical management (AU)


Assuntos
Humanos , Transtorno Bipolar/complicações , Glândula Tireoide , Compostos de Lítio/efeitos adversos , Carbamazepina/efeitos adversos , Doenças da Glândula Tireoide/induzido quimicamente , Fatores de Risco
16.
Clin Endocrinol (Oxf) ; 81(6): 883-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24612232

RESUMO

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.


Assuntos
Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Lipodistrofia/induzido quimicamente , Receptores da Somatotropina/antagonistas & inibidores , Adenoma/metabolismo , Adulto , Antineoplásicos/uso terapêutico , Cabergolina , Quimioterapia Combinada , Ergolinas/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Estudos Retrospectivos , Espanha , Falha de Tratamento , Resultado do Tratamento
17.
Clin Biochem ; 47(6): 464-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24495861

RESUMO

OBJECTIVE: Red blood cell distribution width (RDW) is a hematological parameter that has been studied in several clinical settings and has been found to be related to both anemia and inflammatory status. As obesity is related to increased inflammatory pattern, we aimed to analyze the RDW in this setting. METHODS: We determined hematological and inflammatory parameters in morbidly obese patients before bariatric surgery (n=142) and normo-weight controls (n=144). RESULTS: RDW was higher in patients than in controls (p<0.001), along with C-reactive protein (p<0.001) and fibrinogen, (p<0.001) while hemoglobin (p=0.026), serum iron (p<0.001), MCH (p=0.002) and MCHC (p<0.001) were lower in morbidly obese patients. The logistic correlation analysis revealed that only low serum iron (<62 µg/dL) and MCH (<28.14 pg) levels were associated with RDW>14% (OR 7.61, 95% CI: 1.93-30.04, p=0.004; OR 5.67, 95% CI: 1.98-16.24, p=0.001; respectively). CONCLUSIONS: These data indicate that the elevated RDW in morbidly obese patients reflects a mild red blood cell hypochromia that does not relate to inflammatory parameters, but to hyposideremia and, consequently, to lower erythrocyte indices, possibly as a result of being on a very low-calorie diet before bariatric surgery. Therefore, RDW should not be considered as an inflammatory marker in this clinical setting.


Assuntos
Índices de Eritrócitos , Inflamação/sangue , Inflamação/complicações , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino
18.
Rev Psiquiatr Salud Ment ; 7(2): 88-95, 2014.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24462913

RESUMO

Thyroid disfunction affects negatively emotional stability and worsens the clinical course of bipolar affective disorder. The main stabilizer used in this illness, lithium carbonate has numerous effects on the physiology of the thyroid, with the most significant being the inhibition of thyroid hormone release that may occur at therapeutic levels. These dysfunctions have also been reported most frequently in bipolar patients not undergoing treatment with lithium, and was not completely explained by the effects of this drug. Apart from the numerous medical complications and mood disturbances, the cognitive or perceptual system may also be affected. In fact, the presence of thyroid disease increases the rates of obsessive compulsive disorder, phobias, panic disorder, major depressive disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism, the clinical symptoms and signs can be similar to a melancholic depression or dementia. It is therefore important to know well all these possible complications in daily clinical practice. This review will cover the main thyroid dysfunctions present in bipolar patients, whether ot not produced by treatment with lithium carbonate, and will provide a series of recommendations for clinical management.


Assuntos
Transtorno Bipolar/complicações , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/terapia , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Bócio/induzido quimicamente , Bócio/psicologia , Bócio/terapia , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/psicologia , Hipertireoidismo/terapia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Hipotireoidismo/terapia , Carbonato de Lítio/efeitos adversos , Carbonato de Lítio/uso terapêutico , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/psicologia
19.
Pituitary ; 16(1): 115-21, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22481632

RESUMO

Since 1997 there is an online National Registry of acromegalic patients in Spain (REA). We aimed to study changes in acromegaly treatment and outcomes over the last four decades in Spain. In REA clinical and biochemical data are collected at diagnosis and updated every one to 2 years. We analyzed the first treatment received and the different treatments administered according to decade of diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009. Surgical cure rates according to pretreatment with long-acting somatostatin receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which 698 had accurate follow-up data. Treatment of acromegaly changed over time. Surgery was the main treatment option (83.8 %) and medical treatment was widely used (74.7 %) both maintained over decades, while radiation therapy declined (62.8, 61.6, 42.2 and 11.9 % over decades, p < 0.001). First treatment type also changed: surgery was the first line option up until the last decade in which medical treatment was preferred (p < 0.001). Radiotherapy was barely used as first treatment. Treatment combinations changed over time (p < 0.001). The most common treatment combination (surgery plus medical therapy), was received by 24.4, 16.4, 25.3 and 56.5 % of patients over decades. Medical treatment alone was performed in 7.3, 6, 7.2 and 14.7 % over decades. Type of medical treatment also changed, SRLs becoming the first medical treatment modality in the last decades, whereas dopamine agonist use declined (p < 0.001). Surgical cure rates improved over decades (21, 21, 36 and 38 %, p = 0.002) and were not influenced by SRL pre-surgical use. Acromegaly treatment has changed in Spain in the last four decades. Surgery has been the main treatment option for decades; however, medical therapy has replaced surgery as first line in the last decade and radiotherapy rates have clearly declined. SRLs are the most used medical treatment.


Assuntos
Acromegalia/radioterapia , Acromegalia/cirurgia , Acromegalia/tratamento farmacológico , Adulto , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Software , Espanha
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