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1.
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.

2.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(10): 654-662, dic. 2019.
Artigo em Espanhol | IBECS | ID: ibc-184793

RESUMO

Las enfermedades endocrinas están experimentando un importante incremento de su prevalencia, debido a causas de diversa índole, entre ellas la epidemia de obesidad y de desnutrición, el envejecimiento de la población, pero también el efecto de los disruptores endocrinos, entre otros. Por otra parte, las nuevas tecnologías, tanto a nivel de analítica molecular y genética, de imagen y de nuevos dispositivos terapéuticos, obligan a que la comunidad profesional endocrina en España tenga que estar en constante formación. La conexión con los pacientes a través de sus asociaciones, cada vez más activas, y con la sociedad civil en general, el compromiso profesional y la demanda de diversos colectivos sociales de una atención moderna y equitativa, y a llevar a cabo investigación que facilite la consecución de avances para los pacientes, obligan al especialista en Endocrinología y Nutrición, y a la Sociedad Española de Endocrinología y Nutrición (SEEN), a posicionarse y dar respuesta a todos estos retos. En el presente documento, la SEEN expone sus propuestas y su estrategia hasta el 2022


Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022


Assuntos
Endocrinologia/organização & administração , Sociedades Médicas/organização & administração , Sociedades Médicas/tendências , Estratégias , Endocrinologia/tendências , Sistemas Nacionais de Saúde , Medicina/organização & administração , Promoção da Saúde , Espanha
3.
Endocrinol Diabetes Nutr ; 66(10): 654-662, 2019 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31272927

RESUMO

Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022.

4.
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
5.
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
6.
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
7.
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
8.
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
9.
Neuroendocrinology ; 105(2): 131-140, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27513761

RESUMO

BACKGROUND: The common exon 3 deletion polymorphism of the growth hormone receptor (d3-GHR) is associated with disease severity in acromegaly patients. The GHR antagonist pegvisomant (PEGV) is highly effective in treating severe acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and appears to be more responsive to PEGV, although available results remain conflicting. OBJECTIVE: To assess the influence of d3-GHR on the responsiveness of acromegaly patients to PEGV by compiling the evidence derived from the largest available studies. DESIGN: A systematic review of the literature identified three published studies and one conference abstract. Acromegaly patients (n = 324, 49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of raw data from these studies was performed. RESULTS: No significant effect of the d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels below the upper limit of normal with PEGV, which was defined as the lowest IGF-I level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p = 0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of PEGV monotherapy and combination treatment gave similar results. CONCLUSION: Our findings suggest that the d3-GHR polymorphism has no effect on biochemical disease control in acromegaly, as it is not of added value for either the prediction of PEGV responsiveness or the determination of the required PEGV dose.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/genética , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/genética , Deleção de Sequência , Acromegalia/metabolismo , Éxons , Hormônio do Crescimento Humano/uso terapêutico , Humanos
10.
Endocrine ; 55(1): 231-238, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27704480

RESUMO

Giant prolactinomas are rare tumors characterized by their large size, compressive symptoms, and extremely high prolactin secretion. The aim of this study is to describe our experience with a series of 16 giant prolactinomas cases in terms of clinical presentation, therapeutic decisions, and final outcomes. Retrospective analysis of adult patients diagnosed with giant prolactinomas at the endocrine departments of three university tertiary hospitals. We included 16 patients (43.7 % women); mean age at diagnosis: 42.1 ± 21 years. The most frequent presentation was compressive symptoms. The delay in diagnosis was higher in women (median of 150 months vs. 12 in men; p = 0.09). The mean maximum tumor diameter at diagnosis was 56.9 ± 15.5 mm, and mean prolactin levels were 10,995.9 ± 12,157.8 ng/mL. Dopamine agonists were the first-line treatment in 11 patients (mean maximum dose: 3.9 ± 3.2 mg/week). Surgery was the initial treatment in five patients and the second-line treatment in six. Radiotherapy was used in four cases. All patients but one, are still with dopamine agonists. After a mean follow-up of 9 years, prolactin normalized in 7/16 patients (43.7 %) and 13 patients (81 %) reached prolactin levels lower than twice the upper limit of normal. Mean prolactin level at last visit: 79.5 ± 143 ng/mL. Tumor volume was decreased by 93.8 ± 11.3 %, and final maximum tumor diameter was 18.4 ± 18.8 mm. Three patients are actually tumor free. Giant prolactinomas are characterized by a large tumor volume and extreme prolactin hypersecretion. Multimodal treatment is frequently required to obtain biochemical and tumor control.


Assuntos
Agonistas de Dopamina/uso terapêutico , Procedimentos Neurocirúrgicos/métodos , Hipófise/cirurgia , Neoplasias Hipofisárias/terapia , Prolactinoma/terapia , Radioterapia , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Prolactinoma/sangue , Resultado do Tratamento , Adulto Jovem
11.
Endocrinol. nutr. (Ed. impr.) ; 63(8): 397-408, oct. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-156269

RESUMO

Purpose. To describe real-world use of lanreotide combination therapy for acromegaly. Patients and methods. ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). Results. Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1–6) and 2.1 years (0.4–6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15–505%) in the cabergoline cohort and 156% ULN (15–534%) in the pegvisomant cohort, and decreased to 104% ULN (13–557%) p<0.001 and 86% ULN (23–345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. Conclusion. In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated (AU)


Propósito. Describir el uso de lanreotida en combinación terapéutica en acromegalia en la práctica clínica. Pacientes y métodos. ACROCOMB es un estudio observacional, retrospectivo, de pacientes con acromegalia activa tratados en centros hospitalarios españoles con lanreotida en combinación con cabergolina o pegvisomant entre 2006 y 2011. Se revisaron los datos clínicos de 108 pacientes tratados en 44 departamentos de endocrinología: 61 pacientes recibieron lanreótido/cabergolina (cohorte cabergolina) y 47 lanreotida/pegvisomant (cohorte pegvisomant). Resultados. La edad mediana de los pacientes fue de 50,8 años en la cohorte de cabergolina y 42,7 años en la de pegvisomant. Los tratamientos médicos previos a la combinación con lanreótido fueron análogos de somatostatina (SSA) en monoterapia (40 [66%] pacientes) o agonistas de la dopamina (7 [11%] pacientes) en la cohorte de cabergolina y SSA (29 [62%] pacientes) y pegvisomant en monoterapia (16 [34%] pacientes) en la de pegvisomant. Doce pacientes no habían recibido tratamiento previo y en 4 pacientes se desconocía la terapia previa. La mediana de duración del tratamiento fue de 1,6 años (0,1-6) y 2,1 años (rango 0,4 a 6,3) en las cohortes de cabergolina y pegvisomant, respectivamente. Al inicio del estudio el valor mediano del factor de crecimiento de insulina-I era 149% el límite superior normal (LSN) (15-505%) en la cohorte de cabergolina y 156% LSN (15-534%) en la de pegvisomant. Al final del estudio se redujeron a 104% LSN (13-557%) p<0,001 y 86% LSN (23-345%) p<0,0001, respectivamente. Al final del estudio, se reportaron valores normales de factor de crecimiento de insulina-I ajustados por edad en el 48% de los pacientes tratados con lanreotida/cabergolina y 70% de los tratados con lanreotida/pegvisomant. No hubo cambios significativos en los parámetros hepáticos, cardíacos o glucémicos. Conclusión. En la práctica clínica las combinaciones con lanreotida son una opción útil en el tratamiento de pacientes con acromegalia que no está bien controlada en monoterapia, ya sea con SSA carbegolina o pegvisomant; particularmente, la combinación de lanreotida y pegvisomant tiene una alta eficacia y se tolera bien (AU)


Assuntos
Humanos , Acromegalia/tratamento farmacológico , Somatostatina/análogos & derivados , Agonistas de Dopamina/farmacocinética , Estudos Retrospectivos , Quimioterapia Combinada
12.
Endocrinol Nutr ; 63(8): 397-408, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27448708

RESUMO

PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.


Assuntos
Acromegalia/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Ergolinas/farmacologia , Hormônio do Crescimento Humano/análogos & derivados , Fator de Crescimento Insulin-Like I/metabolismo , Peptídeos Cíclicos/farmacologia , Somatostatina/análogos & derivados , Cabergolina , Agonistas de Dopamina/administração & dosagem , Ergolinas/administração & dosagem , Ergolinas/química , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/química , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/química , Somatostatina/farmacologia
13.
Endocrinol. nutr. (Ed. impr.) ; 63(6): 274-284, jun.-jul. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-153139

RESUMO

Los adenomas hipofisarios son tumores infrecuentes de diagnóstico complejo, cuya heterogeneidad y baja incidencia dificultan estudios a gran escala. El Registro Molecular de Adenomas Hipofisarios (REMAH) nació en 2008 en el seno de la Sociedad Andaluza de Endocrinología y Nutrición (SAEN), como estrategia de cooperación clínico-básica y multicéntrica, para mejorar el diagnóstico y tratamiento de tumores hipofisarios mediante la combinación de información clínica, anatomopatológica y molecular. En 2010, la Sociedad Española de Endocrinología y Nutrición (SEEN) lo extendió a nivel nacional, estableciendo 6 nodos con protocolos y métodos comunes de recogida de muestras y datos clínicos, análisis molecular y anotación en un mismo registro (www.remahnacional.com). El registro combina datos clínicos con el fenotipado molecular del adenoma intervenido, mediante PCR cuantitativa en tiempo real de la expresión de 26 genes: hormonas hipofisarias (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptores (somatostatina, dopamina, GHRH, GnRH, CRH, arginina-vasopresina, ghrelina), otros marcadores (Ki67, PTTG1) y genes de control. Hasta 2015 se ha obtenido información molecular de 704 adenomas, de los 1.179 pacientes registrados. Esta estrategia permite abordar análisis comparativos y relacionales entre el perfil molecular de los distintos tipos de adenomas y el fenotipo clínico del paciente, lo que puede ofrecer un mejor conocimiento de la enfermedad y, potencialmente, ayudar en la selección del tratamiento. El REMAH constituye una red única, multicéntrica e interdisciplinar, cimentada en una base de datos compartida, que aporta un enfoque traslacional de gran proyección potencial para el manejo de los adenomas hipofisarios y abre el camino para estudios conjuntos clínico-básicos innovadores con un elevado número de pacientes (AU)


Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples (AU)


Assuntos
Humanos , Neoplasias Hipofisárias/patologia , Medicina de Precisão , Pesquisa Médica Translacional/métodos , Registros de Doenças/estatística & dados numéricos , Acromegalia/epidemiologia , Síndrome de Cushing/epidemiologia
14.
Endocrinol Nutr ; 63(6): 274-84, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27091627

RESUMO

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples.


Assuntos
Adenoma/epidemiologia , Endocrinologia/organização & administração , Neoplasias Hipofisárias/epidemiologia , Medicina de Precisão/tendências , Sistema de Registros , Pesquisa Médica Translacional/tendências , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Idoso , Criança , Bases de Dados Factuais , Endocrinologia/tendências , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Biologia Molecular , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Hormônios Hipofisários/análise , Hormônios Hipofisários/genética , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Hormônio Hipofisário/análise , Receptores do Hormônio Hipofisário/genética , Sociedades Médicas , Espanha/epidemiologia , Adulto Jovem
15.
Case Rep Endocrinol ; 2016: 2087102, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977326

RESUMO

Pegvisomant (PEGv) is a growth hormone receptor antagonist approved for the treatment of acromegaly; one of its documented adverse effects is reversible elevation of hepatic enzymes. We report a 39-year-old male acromegalic patient with a pituitary macroadenoma who underwent transsphenoidal surgery. The patient's condition improved but GH and IGF-I levels did not normalize; as a consequence, we first administered dopamine agonists and then somatostatin receptor ligands (SRLs) with poor response. PEGv 15 mg every other day was added to lanreotide 120 mg monthly. The patient developed a severe hepatitis five months after starting the combination therapy. Elevated ferritin, iron, and transferrin saturation suggested probable hepatitis due to haemochromatosis. We performed a liver biopsy which showed an acute cholestatic hepatitis consistent with toxic etiology. A heterozygous genotype UGT1A1 (⁎) 28 polymorphism associated with Gilbert's syndrome was also found in this Argentine patient. The predominant clinical presentation resembled an acute cholestatic hepatitis associated with severe hemosiderosis, a different and new pattern of PEGv hepatotoxicity.

16.
Prog Mol Biol Transl Sci ; 138: 85-114, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26940388

RESUMO

In the era of predictive medicine, management of diseases is evolving into a more personal and individualized approach, as more data are available regarding clinical, biochemical, radiological, molecular, histopathological, and genetic aspects. In the particular setting of acromegaly, which is a rare, chronic, debilitating, and disfiguring disease, an optimized approach deems even more necessary, especially because of an associated increased morbidity and mortality, the impact on patients' quality of life, and the increased cost of frequently necessary life-long treatments. In this paper, we review the available studies that address potential genetic influences on acromegaly, their role in the outcome, and response to treatments, as well as their contribution to the risk of developing side effects. We focus mainly on pharmacogenetic factors involved during treatment with dopamine agonists, somatostatin analogs, and pegvisomant. Specifically, mutations in dopamine receptors, somatostatin receptors, growth hormone receptors, and metabolic pathways involved in growth hormone action; polymorphisms in the insulin-like growth factor and the insulin-like growth factor binding proteins; and polymorphisms in other genes that may determine differences in the frequency of developing adverse events.


Assuntos
Acromegalia/tratamento farmacológico , Predisposição Genética para Doença , Acromegalia/genética , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
17.
Clin Endocrinol (Oxf) ; 84(4): 540-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26662620

RESUMO

BACKGROUND: Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established. OBJECTIVE: To re-evaluate the outcomes of long-term PEG in a series of previously published patients and analyse the escape phenomenon. METHODS: We reviewed all patients with acromegaly resistant to SSA in whom PEG was started as monotherapy, who had been included in a previous publication. We prospectively evaluated 64 (56·3% women) from six tertiary care referral hospitals in Spain, for whom data as of June 2014 were available. Escape to PEG was defined as confirmed loss of biochemical control (IGF-I >1·2xULN), after at least 6 months of previous control with a stable dose of PEG. RESULTS: Patients were followed up for 13·0 (5·9-34·8) years since diagnosis, and 9·0 (4·1-10·4) years since the first administration of PEG. Fifty-one (89·5%) patients had an adequate IGF-I control at the last follow-up visit, 9 of them without treatment. Tumour growth was reported in 6 of 64 cases (9·4%), none of whom had received prior radiotherapy (P = 0·011). Seven patients died during follow-up. We found 16 escapes in 10 patients (15·6%). We identified potential underlying causes in 9 cases (tumour regrowth, previous treatment modifications, concomitant menopause and change in testosterone administration). The reason was unknown in 7 escapes, which occurred in 6 patients (9·4%). All patients, except one, achieved subsequent biochemical control after treatment adjustment. CONCLUSIONS: We reassure the efficacy and safety of long-term PEG. An escape phenomenon may occur, but it can be overcome by adjusting therapy.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Acromegalia/metabolismo , Adulto , Idoso , Feminino , Seguimentos , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/metabolismo , Espanha , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
20.
Endocrinol Metab Clin North Am ; 44(1): 151-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25732651

RESUMO

The prevalence of hypopituitarism after traumatic brain (TBI) injury is widely variable in the literature; a meta-analysis determined a pooled prevalence of anterior hypopituitarism of 27.5%. Growth hormone deficiency is the most prevalent hormone insufficiency after TBI; however, the prevalence of each type of pituitary deficiency is influenced by the assays used for diagnosis, severity of head trauma, and time of evaluation. Recent studies have demonstrated improvement in cognitive function and cognitive quality of life with substitution therapy in GH-deficient patients after TBI.


Assuntos
Lesões Encefálicas/complicações , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/etiologia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Hipopituitarismo/tratamento farmacológico
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