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1.
Eur J Endocrinol ; 183(4): 427-437, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688336

RESUMO

Objective: Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) excess results in both reversible and irreversible musculoskeletal damage, including increased vertebral fracture (VF) risk. The prevalence of VFs is approximately 60% in controlled acromegaly patients, and these VFs can progress in time. We aimed to identify the course of VFs in a cohort of acromegaly patients in long-term remission and their associated risk factors during prolonged follow-up. Methods: Thirty-one patients with acromegaly (49% female, median age 60 years (IQR 53-66)), who were in remission for ≥2 years, were included in this longitudinal, prospective, follow-up study. Spine radiographs of vertebrae Th4 to L4 were assessed for VFs using the Genant score, at baseline, after 2.6 years and 9.1 years. Progression was defined as either a new fracture or a ≥1-point increase in Genant score. Results: The prevalence of VF at baseline was 87% (27/31 patients). Progression of VFs was observed in eleven patients (35.5%) during the 9.1-year follow-up period, with a total incidence rate of 65.5 per 1000 person years (males 59.8 per 1000 person years vs females 71.6 per 1000 person years). Patients treated with surgery or radiotherapy had a higher risk of VF progression in this cohort (P = 0.030). Conclusions: In this cohort of long-term, well-controlled acromegalic patients, the prevalence and progression of VFs was high, showing that the deleterious effects of GH and IGF-1 excess on bone persist despite achievement of longstanding remission.


Assuntos
Acromegalia/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/patologia , Acromegalia/etiologia , Acromegalia/terapia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/terapia , Adulto , Idoso , Densidade Óssea , Sobreviventes de Câncer/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia
2.
Eur J Endocrinol ; 183(4): D1-D13, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698136

RESUMO

The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing whether patients with acromegaly should be submitted to specific oncology screening and surveillance protocols. The aim of the present work is to review the most recent data on the risk of either colorectal cancer or thyroid cancer in acromegaly and discuss the opportunity for specific screening in relation to the accepted procedures in the general population.


Assuntos
Acromegalia/complicações , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Programas de Rastreamento , Monitorização Fisiológica , Neoplasias da Glândula Tireoide/diagnóstico , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Endocrinologia/métodos , Endocrinologia/normas , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Oncologia/métodos , Oncologia/normas , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Vigilância da População/métodos , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/epidemiologia
3.
Eur J Endocrinol ; 182(3): 293-302, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917679

RESUMO

Objective: Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes. Design: Two independent observational studies, one being prospective and the other retrospective and cross-sectional. Methods: Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology. Results: Patients with acromegaly had a median (interquartile range) of 34.3 (30.0-39.0) vessel branching points compared to 27.0 (24.0-29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points (34.2 (32.5-35.6)), but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly. Conclusions: Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.


Assuntos
Acromegalia/patologia , Vasos Retinianos/patologia , Acromegalia/complicações , Acromegalia/terapia , Adolescente , Adulto , Idoso , Arteríolas/patologia , Estudos de Casos e Controles , Estudos Transversais , Complicações do Diabetes/patologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Prevalência , Estudos Retrospectivos , Vênulas/patologia , Adulto Jovem
4.
Eur J Endocrinol ; 182(3): 319-331, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958318

RESUMO

Objective: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. Design: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. Methods: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. Results: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. Conclusion: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.


Assuntos
Acromegalia/psicologia , Acromegalia/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Nível de Saúde , Hormônios/deficiência , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Autoimagem , Fatores Sexuais , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
5.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31544947

RESUMO

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP, and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates, since GH potently stimulates collagen turnover. AIM: To measure circulating FGF21 components, including FAP, in patients with acromegaly before and after disease control. METHODS: Eighteen patients with active acromegaly were studied at the time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, ß-klotho, FAP, and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by reverse transcriptase-polymerase chain reaction, body composition assessed by dual-energy x-ray absorptiometry scan, and insulin sensitivity estimated with homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: Total FGF21, active FGF21 and ß-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/L) were markedly reduced after treatment [105.6 ± 29.4 vs 62.2 ± 32.4, P < 0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (P < 0.000) and Type III (P < 0.000). CONCLUSION: 1) Circulating FGF21 and ß-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, and 3) FAP is a hitherto unrecognized GH target linked to collagen turnover. CLINICAL TRIALS REGISTRATION: NCT00647179.


Assuntos
Acromegalia/metabolismo , Biomarcadores/metabolismo , Colágeno/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Gelatinases/metabolismo , Hormônio do Crescimento Humano/metabolismo , Proteínas de Membrana/metabolismo , Serina Endopeptidases/metabolismo , Acromegalia/patologia , Acromegalia/terapia , Adulto , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
6.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801303

RESUMO

Nanoparticles are becoming an increasingly popular tool for biomedical imaging and drug delivery. While the prevalence of nanoparticle drug-delivery systems reported in the literature increases yearly, relatively little translation from the bench to the bedside has occurred. It is crucial for the scientific community to recognize this shortcoming and re-evaluate standard practices in the field, to increase clinical translatability. Currently, nanoparticle drug-delivery systems are designed to increase circulation, target disease states, enhance retention in diseased tissues, and provide targeted payload release. To manage these demands, the surface of the particle is often modified with a variety of chemical and biological moieties, including PEG, tumor targeting peptides, and environmentally responsive linkers. Regardless of the surface modifications, the nano-bio interface, which is mediated by opsonization and the protein corona, often remains problematic. While fabrication and assessment techniques for nanoparticles have seen continued advances, a thorough evaluation of the particle's interaction with the immune system has lagged behind, seemingly taking a backseat to particle characterization. This review explores current limitations in the evaluation of surface-modified nanoparticle biocompatibility and in vivo model selection, suggesting a promising standardized pathway to clinical translation.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/uso terapêutico , Coroa de Proteína/química , Projetos de Pesquisa/tendências , Pesquisa Médica Translacional/métodos , Acromegalia/diagnóstico por imagem , Acromegalia/imunologia , Acromegalia/patologia , Acromegalia/terapia , Anemia/diagnóstico por imagem , Anemia/imunologia , Anemia/patologia , Anemia/terapia , Animais , Bibliometria , Diagnóstico por Imagem/métodos , Modelos Animais de Doenças , Vias de Administração de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Esclerose Múltipla/terapia , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Polietilenoglicóis/química , Coroa de Proteína/imunologia , Propriedades de Superfície
7.
Arch. endocrinol. metab. (Online) ; 63(6): 638-645, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055023

RESUMO

ABSTRACT Acromegaly is an insidious disease, usually resulting from growth hormone hypersecretion by a pituitary adenoma. It is most often diagnosed during the 3rd to 4th decade of life. However, recent studies have shown an increase in the incidence and prevalence of acromegaly in the elderly, probably due to increasing life expectancy. As in the younger population with acromegaly, there is a delay in diagnosis, aggravated by the similarities of the aging process with some of the characteristics of the disease. As can be expected elderly patients with acromegaly have a higher prevalence of comorbidities than younger ones. The diagnostic criteria are the same as for younger patients. Surgical treatment of the pituitary adenoma is the primary therapy of choice unless contraindicated. Somatostatin receptor ligands are generally effective as both primary and postoperative treatment. The prognosis correlates inversely with the patient's age, disease duration and last GH level. Arch Endocrinol Metab. 2019;63(6):638-45


Assuntos
Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Acromegalia/diagnóstico , Acromegalia/fisiopatologia , Acromegalia/terapia , Acromegalia/epidemiologia , Prognóstico
8.
Endocrinol Metab Clin North Am ; 48(4): 779-793, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655776

RESUMO

Hypertension is one of the most frequent complications in acromegaly, with a median frequency of 33.6% (range, 11%-54.7%). Although the pathogenesis has not been fully elucidated, it probably results from concomitant factors leading to expansion of extracellular fluid volume, increase of peripheral vascular resistance, and development of sleep apnea syndrome. Because the effect of normalization of growth hormone and insulinlike growth factor 1 excess on blood pressure levels is unclear, an early diagnosis of hypertension and prompt antihypertensive treatment are eagerly recommended, regardless of the specific treatment of the acromegalic disease and the level of biochemical control attained.


Assuntos
Acromegalia , Anti-Hipertensivos/uso terapêutico , Hipertensão , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/metabolismo , Acromegalia/terapia , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/terapia
9.
Ann Endocrinol (Paris) ; 80 Suppl 1: S10-S18, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31606057

RESUMO

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.


Assuntos
Acromegalia/terapia , Garantia da Qualidade dos Cuidados de Saúde , Melhoria de Qualidade , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/metabolismo , Adenoma/terapia , Técnicas de Diagnóstico Endócrino/tendências , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/epidemiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Hormônio do Crescimento Humano/metabolismo , Humanos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Garantia da Qualidade dos Cuidados de Saúde/tendências
10.
Best Pract Res Clin Endocrinol Metab ; 33(2): 101309, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31405752

RESUMO

Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed.


Assuntos
Adenoma , Efeitos Psicossociais da Doença , Neoplasias Hipofisárias , Acromegalia/epidemiologia , Acromegalia/etiologia , Acromegalia/psicologia , Acromegalia/terapia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/psicologia , Adenoma/terapia , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/psicologia , Neoplasias Hipofisárias/terapia , Qualidade de Vida
11.
Endocrinol Metab Clin North Am ; 48(3): 569-581, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31345524

RESUMO

Pituitary adenomas are common. The impact of pituitary tumors on fertility are mainly caused by oversecretion and/or undersecretion of pituitary hormones or compression of pituitary stalk and normal pituitary tissue by the tumor. Diagnosing and managing pituitary tumors during pregnancy involve many challenges, including the effect of hormone excess or deficiency on pregnancy outcome, changes in the pituitary or pituitary-related hormones, changes in tumor size, and the impact of various treatments of pituitary tumors on maternal and fetal outcomes. This article discusses the diagnosis and treatment of patients with prolactinomas, acromegaly, Cushing disease, and other pituitary tumors during pregnancy.


Assuntos
Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Prolactinoma/diagnóstico , Prolactinoma/terapia , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/etiologia , Acromegalia/terapia , Feminino , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Gravidez , Prolactinoma/complicações , Prolactinoma/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-31212352

RESUMO

Two intact bitches aged 9 and 11 years were referred due to chronic polyuria, polydipsia, vomiting, anorexia and progressive lethargy. On clinical examination, signs of tissue overgrowth (large paws, widened interdental space, pharyngeal stridor) were noticed. Diabetes mellitus (DM) was diagnosed in one dog (case 1) and diabetic ketoacidosis (DKA) in the other (case 2). There were increased IGF-1 values suggestive of hypersomatotropism. Progesterone values and pathological findings of the ovaries and uterus indicated diestrus. Diagnosis of diestrus-induced hypersomatotropism was made and ovariohysterectomy was performed in both dogs. Dog 1 also had multiple mammary neoplasms treated with bilateral mastectomy. Treatment resulted in diabetic remission in case 1 and improved glycaemic control in case 2. Overall, diestrus-induced hypersomatotropism is rare but should be considered in any intact diabetic bitch with acromegalic features. Ovariohysterectomy is recommended and associated with a fair to good prognosis.


Assuntos
Acromegalia , Complicações do Diabetes/complicações , Diestro/fisiologia , Doenças do Cão , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/terapia , Acromegalia/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Cães , Feminino , Histerectomia , Mastectomia
13.
Eur J Endocrinol ; 181(2): R45-R56, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100715

RESUMO

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert physiological actions on the skeleton throughout life, by stimulating longitudinal bone growth in children, the acquisition of bone mass during adolescence and the maintenance of skeletal architecture in adults. When GH and IGF-I are secreted in excess, bone remodeling is enhanced leading to deterioration of bone microstructure and impairment of bone strength. Indeed, acromegaly causes skeletal fragility, and vertebral fractures are reported in a remarkable number of subjects exposed to GH and IGF-I excess. The management of skeletal fragility in acromegaly is a challenge, since the awareness of this complication is low, the prediction of fracture risk is difficult to ascertain, the risk of fractures remains after the control of acromegaly and the effectiveness of bone-active drugs is unknown. This review is an update on bone disorders associated with acromegaly and provides a perspective of possible therapeutic approaches based on emerging pathophysiological and clinical information.


Assuntos
Acromegalia/sangue , Acromegalia/terapia , Gerenciamento Clínico , Hormônio do Crescimento Humano/sangue , Acromegalia/diagnóstico por imagem , Densidade Óssea/fisiologia , Doenças Ósseas/sangue , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/terapia , Remodelação Óssea/fisiologia , Fraturas Ósseas/sangue , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/prevenção & controle , Humanos , Resultado do Tratamento
14.
Eur J Endocrinol ; 181(2): R57-R71, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100716

RESUMO

Acromegaly is a rare and challenging disease calling for management in highly specialised multidisciplinary teams (MDTs). Untreated disease has severe morbidity and a clearly increased mortality. Major attainments have been gained over the latest decades, and therefore, the aim of this review is to discuss recent achievements in modern multimodal therapy of acromegaly performed by MDTs, with an emphasis on an individualised, proactive management from the time of diagnosis to long-term outcome. Treatment by surgery is the only potential curative treatment, however, even with modern techniques still with modest cure rates, leaving the patients to often long-term medical treatment. Treatment strategies have changed dramatically in the Western world over recent years, implying a more proactive treatment algorithm often with a shorter or longer pre-surgical treatment period with somatostatin receptor ligands (SRLs). Not all patients will however respond to primary treatment with conventional SRLs and there has recently been a development of potential biomarkers for response that has been implemented in the clinical routine. By today, multimodal treatment can bring every patient in remission, but still almost a third of all patients are undertreated according to large, international registries. On the other hand, it might be a challenge not to over treat thereby bringing the patient into a state of relative or absolute growth hormone deficiency. Clinical series published during the last decade on treatment of patients with acromegaly have indicated a normalisation of mortality, most probably reflecting the proactive and individualised modern treatment. In conclusion, modern, multimodal treatment seems to have normalised mortality, but still the patients suffer from a high multi-organ morbidity and often multi-pharmacy. Every patient should receive an individualised, proactive treatment in order to improve long-term outcome and to reduce costs for the society.


Assuntos
Acromegalia/sangue , Acromegalia/terapia , Gerenciamento Clínico , Hormônio do Crescimento Humano/sangue , Medicina de Precisão/métodos , Acromegalia/diagnóstico , Terapia Combinada/métodos , Terapia Combinada/tendências , Humanos , Medicina de Precisão/tendências
15.
J Med Case Rep ; 13(1): 106, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31018862

RESUMO

BACKGROUND: Congestive heart failure is rarely observed in patients with acromegaly. Excessive growth hormone secretion and elevation of insulin-like growth factor 1 contribute to pathological changes in myocyte growth and structure, cardiac contractility, vascular function, and in later stage may progress to cardiac dysfunction. Early recognition of the condition is paramount, though the insidious progression of the disease commonly results in late diagnosis. Current standard regimens of pharmacological therapy, surgical treatment, radiotherapy are designed to normalize serum levels of both insulin-like growth factor 1 and growth hormone. In patients with late-stage heart failure due to acromegalic cardiomyopathy, cardiac resynchronization therapy might be a desirable treatment to help cardiac synchronization, improve symptoms, and eventually reduce hospital admissions together with mortality rates. CASE PRESENTATION: We describe a case of a 49-year-old man with a history of acromegaly who presented to our hospital with a diagnosis of decompensated systolic heart failure. Serial electrocardiograms showed wide (160-200 ms) QRS duration with left bundle branch block. Echocardiography showed severe left ventricular dysfunction that simultaneously achieved a left ventricular ejection fraction of 16%. Surgical indication was rarely assessed by neurosurgeons. Given that the stereotactic radiosurgery together with pharmacotherapy produced infinitesimal effects, cardiac resynchronization therapy was performed. Owing to biventricular synchronization and holding back reverse remodeling, the patient's symptoms were successfully alleviated, and he was discharged from the hospital. CONCLUSIONS: Congestive heart failure is a rare complication in acromegaly-induced cardiomyopathy (occurs in only 3% of patients). Early diagnosis and treatment with curative drugs more than cardiovascular implantable electronic devices might lead to better surgical outcomes in this group of patients.


Assuntos
Acromegalia/fisiopatologia , Terapia de Ressincronização Cardíaca , Cardiomiopatias/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Acromegalia/complicações , Acromegalia/terapia , Cardiomiopatias/congênito , Cardiomiopatias/terapia , Ecocardiografia , Insuficiência Cardíaca/congênito , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
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
17.
Endokrynol Pol ; 70(1): 74-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843180

RESUMO

Acromegaly is a rare, chronic condition caused by growth hormone (GH) overproduction, usually due to a benign tumour of the pituitary gland. During the disease many complications occur, including cardiovascular disease and changes in the musculoskeletal, respiratory, and endocrine systems. Treatment includes surgery, medical therapy, and radiation. In this paper a literature review was conducted for information related to costs of management of acromegaly and its associated comorbidities using PubMed.The majority of total costs represent pharmacological treatment, especially the most common somatostatin analogues (SSA) therapy. The average reported annual cost of SSA therapy is EUR 12,000-40,000. Surgery reduces the cost of care via the possibility of avoiding lifelong pharmacological treatment. Radiotherapy is also suggested to lower the costs of therapy because about 60% of patients eventually will not require further pharmacological treatment; however, it is connected with negative outcomes like hypopituitarism, lower quality of life, and increased mortality. Cabergoline and pegvisomant are the lowest and highest priced treatments, respectively, but the overall impact on the cost of therapy is minor due to less frequent usage of these drugs. It is hard to fully estimate the impact of comorbidities of acromegaly on financial burden because patients are treated for them many years before the diagnosis of the underlying pathology. The treatment cost of comorbidities is higher in uncontrolled patients. Life-long treatment of acromegaly and its comorbidities is very expensive. Early diagnosis and successful treatment reduce direct and indirect costs.


Assuntos
Acromegalia/terapia , Custos e Análise de Custo , Gerenciamento Clínico , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Feminino , Humanos , Masculino , Somatostatina/uso terapêutico
19.
J Formos Med Assoc ; 118(10): 1430-1437, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30612883

RESUMO

BACKGROUND/PURPOSE: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. RESULTS: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 µg/L, 2.4 ± 6.1 µg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 µg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. CONCLUSION: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly.


Assuntos
Acromegalia/diagnóstico , Acromegalia/terapia , Adenoma/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Qualidade de Vida , Acromegalia/sangue , Acromegalia/epidemiologia , Adenoma/complicações , Adenoma/terapia , Adulto , Glicemia/metabolismo , Feminino , Seguimentos , Galactorreia/etiologia , Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Taiwan/epidemiologia , Adulto Jovem
20.
Eur J Endocrinol ; 180(3): 201-211, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566903

RESUMO

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach. Results One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07-6.78), 2.84 (1.24-6.51) and 2.38 (1.11-5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model. Conclusions Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.


Assuntos
Absorciometria de Fóton , Acromegalia/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Acromegalia/complicações , Acromegalia/terapia , Adulto , Idoso , Índice de Massa Corporal , Peso Corporal , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Hipogonadismo/epidemiologia , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia
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