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1.
Ann Endocrinol (Paris) ; 81(1): 11-17, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31982107

RESUMO

OBJECTIVE: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly. METHODS: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively). RESULTS: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome. CONCLUSIONS: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.


Assuntos
Acromegalia/metabolismo , Acromegalia/cirurgia , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/diagnóstico , Acromegalia/patologia , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Recidiva , Estudos Retrospectivos , Via Secretória/fisiologia , Resultado do Tratamento
2.
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
3.
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
4.
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
5.
Pituitary ; 22(6): 601-606, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556014

RESUMO

INTRODUCTION: Axial skeleton arthropathy and osteoporotic vertebral fractures are common findings in acromegalic patients and can result in severe spinal deformity. OBJECTIVE: To investigate the presence of spinal fractures and deformities, sagittal imbalances, and spinopelvic compensatory mechanisms in acromegalics. PATIENTS AND METHODS: 58 patients with acromegaly from a referral neuroendocrinology center were prospectively evaluated by panoramic spine radiographs to detect the presence of fractures and scoliosis, to measure thoracic kyphosis, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sagittal vertical axis (SVA). Sagittal imbalance criteria were considered: thoracic kyphosis > 50°, PI-LL > 10°, PT > 20° and SVA > 5 cm. Their medical records were analyzed for clinical and laboratorial data. RESULTS: The prevalence of fractures was 13.8%, predominantly in the thoracic spine, with mild and anterior wedge compressions. Scoliosis was present in 34.5% of the cases, all with degenerative lumbar curve apex. Thoracic kyphosis > 50º occurred in 36.8% of patients, PI-LL > 10° in 48.3%, PT > 20° in 41.4% and SVA > 5 cm in 12.1%. CONCLUSION: Increased number of vertebral fractures and high prevalence of spinal deformities related to sagittal imbalance were detected, indicating the importance of monitoring bone comorbidities in acromegaly, with radiological evaluation of the spine as part of the follow up.


Assuntos
Acromegalia/patologia , Acromegalia/diagnóstico por imagem , Acromegalia/metabolismo , Acromegalia/cirurgia , Adulto , Idoso , Cabergolina/uso terapêutico , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/cirurgia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Lordose/diagnóstico por imagem , Lordose/tratamento farmacológico , Lordose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Estudos Prospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/tratamento farmacológico , Fraturas da Coluna Vertebral/cirurgia
6.
Diabetes Metab Syndr ; 13(2): 901-903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336543

RESUMO

Patients with acromegaly have soft tissue overgrowth that induced characteristic clinical presentation. A growth hormone-secreting adenoma of the anterior pituitary gland is the most common cause of acromegaly. Metabolic and somatic features of acromegaly caused by high serum concentrations of insulin-like growth factor-I (IGF-I) and excess growth hormone (GH) production. we present a case of 'pseudoacromegaly' with an acromegaloid features, suppressed IGF-I levels and marked elevation of serum insulin. Endocrinologists should consider this diagnosis when assessing patients with clinical features of acromegaly and insulin resistance, in the absence of elevated levels of GH and IGF-I.


Assuntos
Acromegalia/patologia , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Insulina/efeitos adversos , Acromegalia/induzido quimicamente , Acromegalia/complicações , Adulto , Feminino , Humanos , Prognóstico , Adulto Jovem
7.
Ann Endocrinol (Paris) ; 80(4): 196-201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227172

RESUMO

PURPOSE: Acromegaly causes multiple comorbidities, including gastrointestinal disorders. The present study evaluated the frequency of hiatal hernia and other upper gastrointestinal pathologies in patients with acromegaly, given that visceromegaly and reduced nitric oxide levels in acromegaly may impact diaphragm and lower esophageal sphincter function and thus possibly the development of hiatal hernia. METHODS: Thirty-nine acromegaly patients followed our center for the previous 6months were recruited. Upper gastrointestinal endoscopy was performed once in all patients to evaluate hiatal hernia, esophagitis, gastroduodenitis and ulcer. RESULTS: Twenty-three patients were male and 16 female. Upper gastrointestinal endoscopy found hiatal hernia, esophagitis and gastroduodenitis or gastric ulcer in 3 (7.6%), 2 (1.7%) and 31 (79.4%) patients, respectively. Pathologic examination of gastric antrum biopsy found intestinal metaplasia in 12 (30.7%) patients, and Helicobacter pylori was positive in 13 (33.3%). There were no significant correlations between age, gender, disease duration or preoperative adenoma size on the one hand and hiatal hernia or other endoscopic findings on the other. Similarly, neither surgical success nor recurrence was associated with endoscopic findings. CONCLUSIONS: The study showed that prevalence of gastritis, duodenitis, peptic ulcer and intestinal metaplasia is higher and prevalence of hiatal hernia lower in acromegaly patients than in the healthy population. Various unknown disease-related pathophysiological conditions may play a role; there is a need for further studies.


Assuntos
Acromegalia/complicações , Acromegalia/epidemiologia , Gastroenteropatias/epidemiologia , Trato Gastrointestinal Superior/patologia , Acromegalia/patologia , Adulto , Endoscopia Gastrointestinal , Esofagite/complicações , Esofagite/diagnóstico , Esofagite/epidemiologia , Feminino , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/epidemiologia , Gastroenteropatias/complicações , Gastroenteropatias/diagnóstico , Hérnia Hiatal/complicações , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/complicações , Úlcera Péptica/diagnóstico , Úlcera Péptica/epidemiologia , Prevalência , Trato Gastrointestinal Superior/diagnóstico por imagem
9.
Endokrynol Pol ; 70(2): 213-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30742299

RESUMO

Acromegaly is associated with increased growth hormone (GH) and insulin-like growth factor-I (IGF-I) secretion which may support tumour development and growth. A 68-year-old woman was diagnosed with acromegaly due to typical clinical and hormonal characteristics. While contrast-enhanced MRI at diagnosis did not reveal a pituitary adenoma, a 5-mm lesion was identified on repeat scanning 13 months later. Abdominal and chest CT showed tumours of the stomach, right adrenal gland, and right lung. The CT also showed a hypodense lesion in the liver and heterogeneous echostructure of the thyroid gland with left lobe solid-cystic tumour. Somatostatin receptor scintigraphy revealed increased tracer accumulation in the right thyroid lobe. No tracer accumulation was noted at the location of the other tumours. The resected stomach, adrenal, chest, and thyroid lesions did not show GH secretion. The patient refused pituitary surgery, and her acromegaly is currently well-controlled with somatostatin analogue therapy. A CT scan 19 months later revealed a contrast-enhancing left kidney tumour that was a G1-grade clear cell carcinoma. Four years after the acromegaly diagnosis multiple myeloma were diagnosed with secondary renal amyloidosis. Genetic screening for a paraganglioma gene panel, AIP, MEN1, and CDKN1B mutations were negative. A next-generation cancer panel containing 94 cancer genes did not identify any possible unifying gene abnormality in her germline DNA. Coexistence of acromegaly and numerous other tumours suggests a common aetiology of these disorders. However, no genetic abnormality could be identified with the tests that have been performed.


Assuntos
Acromegalia/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias Intestinais/complicações , Neoplasias Renais/complicações , Neoplasias Pulmonares/complicações , Neoplasias Primárias Múltiplas/complicações , Tumores Neuroendócrinos/complicações , Neoplasias Pancreáticas/complicações , Neoplasias Gástricas/complicações , Acromegalia/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Idoso , Feminino , Humanos , Neoplasias Intestinais/patologia , Neoplasias Renais/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/patologia
10.
Growth Horm IGF Res ; 45: 17-19, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30772778

RESUMO

The GH-receptor antagonist pegvisomant (PEG) reduces peripheral IGF-1 synthesis and is used to treat acromegaly patients resistant or intolerant to somatostatin analogues (SSA). Medical therapy is generally life-long in patients with acromegaly, since disease remission is very uncommon after SSA discontinuation and has never been reported after PEG withdrawal. Here, we report for the first time the cases of two acromegaly patients treated with PEG monotherapy for many years because of resistance to SSA, who persistently maintained normal serum IGF-1 levels after PEG withdrawal. The first patient autonomously discontinued PEG treatment after 8 years, while in the second case we stopped the treatment after 11 years, because slight hypertransaminasemia occurred. After PEG discontinuation, in both cases IGF-1 values remained persistently normal and GH during OGTT regularly suppressed. To date, both patients are still in remission. Therefore, we suggest that PEG could exert unknown antitumoral effects in pituitary tumor cells and that long-term PEG treatment can induce acromegaly remission in some patients.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Suspensão de Tratamento , Acromegalia/patologia , Adulto , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Prognóstico , Indução de Remissão
11.
Ann Endocrinol (Paris) ; 80(2): 110-116, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612694

RESUMO

Acromegaly can impair quality of life, but impact on patients' daily life, needs and expectations have been poorly explored. OBJECTIVES: To better understand the impact of acromegaly on patients' daily life, and evaluate their needs and expectations. PATIENTS AND METHODS: An on-line questionnaire survey of acromegaly patient and relative community members was conducted on the Carenity website. RESULTS: Twenty-five patients and 3 relatives, with a mean age of 48.9 years, responded. Diagnosis of acromegaly was recent (60% within 10 years). Signs at diagnosis were mainly clinical (fatigue, headache) and physical changes (acral enlargement). Reported complications comprised morphological changes (93%), bone and joint symptoms (75%) and metabolic disorders (75%). Pain and fatigue impacted the daily life of 61% and 54% patients, respectively. Acromegaly had strong impact on mood (79%), leisure (75%) and social life (71%). Patients mostly got information from specialized websites (71%), their endocrinologist (61%) and patient associations (54%). The information sought was patient testimony (82%), practical advice (64%), and information on clinical trials (61%) and treatments (50%). Patients wished to have patient-physician discussion groups (25%), and better knowledge of acromegaly on the part of those they were in contact with (25%). CONCLUSION: Acromegaly has a major impact on patients' daily life and mood. Patients wished their disease to be better known, and advocated setting up discussion groups. This study should encourage acromegaly education programs to adapt the services and information that are needed by acromegalic patients.


Assuntos
Acromegalia/epidemiologia , Acromegalia/psicologia , Atividades Cotidianas , Motivação , Qualidade de Vida , Acromegalia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Feminino , França/epidemiologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Motivação/fisiologia , Inquéritos e Questionários , Adulto Jovem
12.
Pituitary ; 22(2): 113-123, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30637623

RESUMO

PURPOSE: To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population. METHODS: We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed. RESULTS: The mean age at pituitary adenoma diagnosis was 53.9 ± 17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p = 0.002). PHPT and adrenocortical adenomas can be managed with elective surgery. CONCLUSIONS: The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.


Assuntos
Adenoma/epidemiologia , Neoplasia Endócrina Múltipla Tipo 1/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Acromegalia/epidemiologia , Acromegalia/patologia , Acromegalia/cirurgia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Prolactinoma/epidemiologia , Prolactinoma/patologia , Prolactinoma/cirurgia , Estudos Retrospectivos
13.
Pituitary ; 22(1): 70-78, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30607746

RESUMO

PURPOSE: Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs. METHODS: We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST1, SST2, SST3, SST5 and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST1-5 and D2DR was further evaluated by western blot. RESULTS: Mean patient age was 61.8 years (range 47-71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST1 was noted in 1/5 cases, SST2 in 2/5 cases, including recurrent case but not the original case. SST3 was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST2, SST3 and D2DR expression was identified in all the samples, including two cases originally negative for SST2 and one case negative for SST3 by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST5 was observed. In the patient with the recurrent tumor, intensity of SST2, SST3 and D2DR expression varied between original tumor and its recurrence. CONCLUSIONS: We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST2 and SST3, while no expression of SST5 was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.


Assuntos
Adenoma Oxífilo/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Somatostatina/metabolismo , Acromegalia/metabolismo , Acromegalia/patologia , Adenoma Oxífilo/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Doenças da Glândula Tireoide/metabolismo , Doenças da Glândula Tireoide/patologia
14.
J Endocrinol Invest ; 42(7): 825-831, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30488289

RESUMO

PURPOSE: Biomarkers of clinical and therapeutic outcome in acromegaly are needed. Polymorphisms or epigenetic changes of detoxification genes, such as those coding for the aryl hydrocarbon receptor (AHR) and the glutathione-S-transferase-P1 (GSTP1), could have a role in GH secreting pituitary tumors' pathophysiology and clinical expression. In this study, we assessed the contribution of GSTP1 gene promoter methylation status, per se or in combination with the occurrence of the AHR gene rs2066853 variant, on clinical features and response to somatostatin analogs (SSA) treatment in acromegaly patients. METHODS: This is an observational, retrospective study, carried out in the Endocrine Unit of an Italian University Hospital. We enrolled 77 wild-type AIP gene acromegaly patients, who have been screened for germline AHR rs2066853 variant and GSTP1 gene promoter methylation. Clinical and biochemical parameters were compared after patients' stratification according to GSTP1 methylation status and the presence of AHR rs2066853. We also evaluated the response to SSA treatment in 71 cases. RESULTS: 17 patients carried the AHR rs2066853 variant and 26 had methylated GSTP1 (GSTP1-methyl) gene promoter. GSTP1-methyl patients showed a higher prevalence of diabetes mellitus (p = 0.01), colonic polyps (p = 0.05), and were more resistant to SSA (p = 0.02) as compared to GSTP1 unmethylated patients (GSTP1-unmethyl). Patients GSTP1-unmethyl and AHR wild-type were the most sensitive to SSA treatment, while those with both GSTP1-methyl and AHR rs2066853 variant were all resistant to SSA (p = 0.01). CONCLUSIONS: In acromegaly, GSTP1 gene methylation associates with resistance to SSA treatment, especially in patients carrying also the AHR rs2066853 variant, and with increased prevalence of colonic polyps and diabetes mellitus.


Assuntos
Acromegalia/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/análise , Resistência a Medicamentos/genética , Glutationa S-Transferase pi/genética , Octreotida/uso terapêutico , Polimorfismo Genético , Receptores de Hidrocarboneto Arílico/genética , Acromegalia/tratamento farmacológico , Acromegalia/patologia , Antineoplásicos Hormonais/uso terapêutico , Metilação de DNA , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Estudos Retrospectivos
15.
Artigo em Inglês | MEDLINE | ID: mdl-30088454

RESUMO

BACKGROUND AND OBJECTIVE: Giant pituitary adenomas (GPAs) are benign tumours with a diameter ≥ 4 cm [1]. They can cause symptoms and signs due to the possible hyper-secretion of one or more pituitary hormones, and involvement of the surrounding structures whereas the compression of the pituitary itself can lead to hypopituitarism. METHODS: We report on a young woman with acromegaly due to an inoperable giant GH-secreting pituitary adenoma extending to right cavernous sinus, right orbital cavity, ethmoid, right maxillary sinus, sphenoid sinus, clivus and right temporal fossa, in which medical treatment with Octreotide- LAR was able to promptly relieve headache and bilateral hemianopsia due to optic chiasm involvement, improve acromegaly symptoms and, over the time, control tumor expansion, improving fertility and therefore allowing the patient to become pregnant. RESULTS: Octreotide-LAR therapy was withdrawn during pregnancy and the patient did not experience complications and gave birth to a healthy son. On magnetic resonance, the size of the tumor at the end of pregnancy and in the subsequent follow up was not increased. CONCLUSION: The history we report, therefore, confirms previous experiences reporting a possible favourable outcome of pregnancy in patients affected by acromegaly and adds further information about the behaviour of giant pituitary tumors in patients underwent pregnancy.


Assuntos
Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Octreotida/uso terapêutico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Acromegalia/patologia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/patologia , Adulto , Antineoplásicos Hormonais/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Hemianopsia/diagnóstico , Hemianopsia/tratamento farmacológico , Hemianopsia/etiologia , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/tratamento farmacológico , Síndromes de Compressão Nervosa/etiologia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Carga Tumoral
16.
Minerva Endocrinol ; 44(2): 129-136, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30531694

RESUMO

Acromegaly is mainly due to the somatotroph pituitary neuroendocrine tumors (PitNET)s. These have been subtyped into densely granulated (DG) and sparsely granulated (SG) tumors, which differ in clinical, histological and biological characteristics and in response to somatostatin analogs (SA)s. The variable remission rate after surgical resection, as first line treatment, has increased interest in identifying pathological markers to better predict the response to medical treatment. Several techniques have shown somatotroph tumors to express somatostatin receptors (SSTR)s, and mainly SSTR2 and SSTR5. The molecular methods appear to give contradictory results, are expansive and cannot be routinely performed. Immunohistochemistry, while being the most powerful technique, requires optimal fixation and the use of monoclonal antibodies against at least SSTR2 and SSTR5. Almost all somatotroph tumors express SSTR2 or SSTR5, and, in great majority, at a high level. More importantly, the type of SSTR, the level of expression, and the response to SA treatment appear well correlated. Indeed, a significantly higher expression of SSTR2 in DG compared to in SG tumors likely explains the better response of DG tumors to the normalization of growth hormone and insulin-like growth factor-1 under SA. However, a reproducible scoring and a cut-off from which the SA efficacy can be reliably predicted, remain to be found. In conclusion, the SSTR expression profile and morphological subtypes of the somatotroph tumor may help predict the response to medical treatment. Such pathological profiling could become a useful decision-making tool for clinicians in the context of a multidisciplinary approach, after surgery failure.


Assuntos
Adenoma/tratamento farmacológico , Adenoma/patologia , Biomarcadores/análise , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Acromegalia/tratamento farmacológico , Acromegalia/patologia , Animais , Humanos , Valor Preditivo dos Testes , Prognóstico , Receptores de Somatostatina/genética
17.
Cancer Chemother Pharmacol ; 83(2): 375-385, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30535537

RESUMO

PURPOSE: Octreotide SC depot is a novel, ready-to-use formulation administered via a thin needle. In a phase 1 study in healthy volunteers, this formulation provided higher bioavailability of octreotide with faster onset and stronger suppression of IGF-1 in healthy volunteers versus long-acting intramuscular (IM) octreotide. This phase 2 study evaluated the pharmacokinetics, efficacy, and safety of octreotide SC depot in patients with acromegaly and functioning NETs, previously treated with octreotide IM. METHODS: Adult patients with acromegaly or functioning NETs treated for ≥ 2 months with octreotide IM [10/20/30 mg every 4 weeks (q4w)] received the last dose of octreotide IM treatment in study period 0 and were randomized 28 days later to receive octreotide SC depot 10 mg q2w, or 20 mg q4w for 3 months (period 1). The primary objective was to characterize the PK profile of octreotide SC depot after each injection vs PK for octreotide IM (period 0). RESULTS: Twelve patients were randomized to receive octreotide SC depot 10 mg q2w (acromegaly n = 3; NET n = 1) or 20 mg q4w (acromegaly n = 4; NET n = 4). Plasma levels of octreotide were higher with octreotide SC depot as compared to octreotide IM. Adverse events were reported in 6 and 8 patients during period 0 and period 1, respectively; most common in period 1 were gastrointestinal disorders. CONCLUSION: Octreotide SC depot provided higher exposure (AUC) than octreotide IM, maintained biochemical control in patients with acromegaly and symptom control in patients with functioning NETs, and was well tolerated with a safety profile consistent with octreotide IM. CLINICALTRIALS. GOV IDENTIFIER: NCT02299089.


Assuntos
Acromegalia/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/farmacologia , Octreotida/farmacocinética , Acromegalia/complicações , Acromegalia/metabolismo , Acromegalia/patologia , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Prognóstico , Taxa de Sobrevida , Distribuição Tecidual
18.
J Clin Endocrinol Metab ; 104(5): 1637-1644, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476255

RESUMO

CONTEXT: A paradoxical GH response to oral glucose (OG) is often found in acromegaly. However, the clinical characteristics of patients with acromegaly and a paradoxical GH response to OG (OG responders) remain unclear. OBJECTIVE: The aim of the present study was to define the clinical characteristics of OG responders with acromegaly. DESIGN: Retrospective study. SETTING: Hospitalized care at Osaka University Hospital. PATIENTS AND METHODS: Of 63 patients with acromegaly admitted to our hospital from January 2006 to January 2017, 19 were classified as OG responders and 44 as nonresponders. The clinical characteristics of these groups were compared. RESULTS: Before surgery, OG responders had substantially greater IGF-1 SD scores than nonresponders (P < 0.05), although no difference was found in basal GH levels between the two groups (P = 0.46). Regarding glucose metabolism, 120-minute plasma glucose and immunoreactive insulin after OG administration and hemoglobin A1c were significantly greater in OG responders than in nonresponders (P < 0.01, P < 0.05, P < 0.05, respectively). GH levels during octreotide or bromocriptine testing were decreased more significantly in OG responders than in nonresponders (P < 0.05, P < 0.05, respectively). The proportion of pituitary tumors with hypointensity on T2-weighted MRI was significantly greater in OG responders than in nonresponders (P < 0.05). The difference in IGF-1 and parameters of glucose metabolism described disappeared between the two groups after surgery. CONCLUSIONS: The paradoxical GH response reflected the clinical characteristics, especially IGF-I level, glucose metabolism, and drug efficacy in acromegaly. A paradoxical GH response, in addition to the nadir GH levels, to OG load is potentially useful for evaluation of the clinical characteristics of acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Glucose/administração & dosagem , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Acromegalia/metabolismo , Acromegalia/patologia , Adulto , Biomarcadores/análise , Bromocriptina/farmacologia , Estudos de Casos e Controles , Feminino , Seguimentos , Fármacos Gastrointestinais/farmacologia , Glucose/metabolismo , Antagonistas de Hormônios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/farmacologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Prognóstico , Estudos Retrospectivos
19.
Pituitary ; 21(6): 615-623, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30367444

RESUMO

PURPOSE: To determine whether pre-surgical medical treatment (PSMT) using long-acting Somatostatin analogues in acromegaly may improve long-term surgical outcome and to determine decision making criteria. METHODS: This retrospective study included 110 consecutive patients newly diagnosed with acromegaly, who underwent surgery in a reference center (Marseille, France). The mean long-term follow-up period was 51.4 ± 36.5 (median 39.4) months. Sixty-four patients received PSMT during 3-18 (median 5) months before pituitary surgery. Remission was defined at early (3 months) evaluation and at last follow-up by GH nadir after oral glucose tolerance test < 0.4 µg/L and normal IGF-1. RESULTS: Pretreated and non-pretreated groups were comparable for the main confounding factors except for higher IGF-1 at diagnosis in PSMT patients. Remission rates were significantly different in pretreated or not pretreated groups (61.1% vs. 36.6%, respectively at long-term evaluation). In multivariate analysis, PSMT was significantly linked to 3 months (p < 0.01) and long-term remission (p < 0.01). Duration of PSMT was not significantly different in cured or non-cured patients, at both evaluation times. PSMT appeared to be more beneficial for patients with an invasive tumor. No patient with a tumor greater than 18 mm or mean GH level exceeding 35 ng/mL at diagnosis was cured by surgery alone (vs. 8 and 9 patients in the pretreated group, respectively). Patients with PSMT showed more transient mild hyponatremia after surgery. CONCLUSIONS: PSMT significantly improved short and long-term remission in patients with acromegaly, independent of its duration, especially in invasive adenomas.


Assuntos
Acromegalia/patologia , Neoplasias Hipofisárias/patologia , Acromegalia/metabolismo , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Prognóstico , Estudos Retrospectivos , Tireotropina/metabolismo
20.
Wien Klin Wochenschr ; 130(17-18): 511-516, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30062505

RESUMO

BACKGROUND: Regarding the incidence of colorectal malignancy and polyps in patients with acromegaly, studies reported different results in different populations. For this reason, the aim of this study was to determine the frequency of possible colonic pathologies, such as diverticula, polyps, and malignancies in Turkish patients with active acromegaly and factors affecting them. METHODS: A total of 134 patients with acromegaly and 134 patients with irritable bowel syndrome/dyspeptic symptoms as a control group were included in the study. None of these patients had a previous or family history of colonic neoplasms. Colonoscopies of patients with acromegaly were performed before definitive surgery in a single center by experienced endoscopists. RESULTS: The acromegaly and control groups were similar in terms of age and sex. The incidence of all colonic polyps was significantly higher in the acromegaly group (p = 0.012). The frequency of hyperplastic polyps was also increased in the acromegaly group (p = 0.004); however, the frequencies of adenomatous polyps and colonic diverticula were similar in both groups. In the comparison of patients with acromegaly for the presence of polyps, those with polyps were older, had higher levels of insulin-like growth factor (IGF-1), were of male sex, and skin tags were more common (p = 0.016, p = 0.034, p = 0.006 and p = 0.001, respectively). There were no colorectal malignancies in the patients with active acromegaly. CONCLUSION: The frequency of hyperplastic polyps was increased, whereas colonic malignancy was not observed in Turkish patients with active acromegaly.


Assuntos
Acromegalia , Pólipos do Colo/complicações , Acromegalia/complicações , Acromegalia/patologia , Pólipos do Colo/epidemiologia , Colonoscopia , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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