Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
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
2.
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
3.
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
4.
Pituitary ; 18(6): 782-95, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25820377

RESUMO

PURPOSE: To assess the long-term impact of postoperative two-field-conventional radiotherapy (RT) on neurocognitive functions of adult patients with operated pituitary adenomas (PA). METHODS: We selected 124 adult patients with operated PA-56 of whom had also received RT-recorded their main clinical data and performed a neuropsychological assessment in all of them that included 15 standardized tests, and a cerebral SPECT in eight patients. Comparative analyses were carried out on major clinical and neurocognitive domains between irradiated and not irradiated patients, and on cerebral SPECT source. RESULTS: Compared with non-irradiated patients, irradiated patients performed significantly worse on Barcelona's story recall test (P < 0.001) and arithmetic problems (P < 0.03) and on five categories of the Wisconsin card sorting test, especially on perseverative answers and errors (P < 0.001) without differences in other examined functional domains. RT was the only factor associated with worse results in these tests regardless other clinical and treatment-related variables. Kaplan-Meier analysis suggested that the probability of achieving poorer results with time was related to RT total dose and field-size, type of PA and age at the time of RT. Four of the five SPECTS performed in irradiated patients revealed a similar altered perfusion in the left temporal lobe cortical region. CONCLUSIONS: In adult patients with operated PA, RT was independently associated with an impairment on verbal memory and executive function, when compared to non-irradiated patients. Our data suggest that diagnosis of acromegaly or Cushing's disease, and age at the time of RT were able to modulate this long-term radio-induced neurocognitive sequelae.


Assuntos
Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/radioterapia , Radioterapia/efeitos adversos , Acromegalia/complicações , Adulto , Fatores Etários , Cognição/efeitos da radiação , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Hipersecreção Hipofisária de ACTH/complicações , Neoplasias Hipofisárias/cirurgia
5.
Eur J Endocrinol ; 172(2): 115-22, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25385818

RESUMO

OBJECTIVE: IGF1 and IGFBP3 gene polymorphisms have been recently described. However, their potential role in the setting of acromegaly and its outcome is unknown. In this study, we analyze these polymorphisms in patients with acromegaly and investigate their association with clinical presentation and response to treatments. DESIGN: A retrospective observational study was conducted in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms. METHODS: A total of 124 patients with acromegaly (57.3% women, mean age 44.9±13.1 years old) were followed up for a period of 11.4±8.0 years in eight tertiary referral hospitals in Spain. Clinical and analytical data were evaluated at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed using PCR and specific primers. RESULTS: Baseline laboratory test results were GH 19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65±1.25 upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any association between the number of cyto-adenosine (CA) repeats and patients' baseline characteristics. Nevertheless, a trend for higher nadir GH values was observed in patients with <19 CA repeats. Regarding the IGFBP3 polymorphism, the absence of an A allele at the -202 position was associated with a higher baseline IGF1 and a higher prevalence of cancer and polyps. There were no differences in response to therapies according to the specific genotypes. CONCLUSIONS: Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of treatment outcome in acromegalic patients, but they may be associated with higher nadir GH levels or baseline IGF1, and determine a higher rate of colorectal polyps and cancer.


Assuntos
Acromegalia/diagnóstico , Acromegalia/genética , Estudos de Associação Genética/métodos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Polimorfismo Genético/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
6.
An R Acad Nac Med (Madr) ; 131(1): 289-302; discussion 302-5, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-27386685

RESUMO

The Diffuse Large B-Cell Lymphoma is the most frequent non Hodgkin Lymphoma. The role of CT/PET in this relatively homogeneous group of lymphomas is controversial. It rarely changes the management of the patients in the initial staging. Recents publications, clinical trials and experts consensus meetings have demonstrated its utility in the evaluation of the response at the end of the treatment. The interest of CT/PET in the evaluation of the response during the treatment, with the objective of implement a "Risk Adapted Therapy", in increasing.


Assuntos
Células Epiteliais , Neoplasias Orofaríngeas/patologia , Humanos
7.
Eur J Endocrinol ; 168(1): 9-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23038625

RESUMO

OBJECTIVE: Most cases of familial isolated pituitary adenomas with mutated aryl hydrocarbon receptor-interacting protein (AIP:HGNC:358) gene develop somatotropinomas. They are characterised by an aggressive clinical phenotype including early age at diagnosis, large tumours and frequent invasiveness. There is little information on AIP gene mutations' prevalence in isolated somatotropinomas characterised by poor response to somatostatin analogue treatment. The aim of this study was to investigate the prevalence of AIP mutations in non-familial cases of somatotropinomas with poor response to conventional treatment. DESIGN AND METHODS: Fifty patients with acromegaly (22 males/28 females, age 51±18 years) and 60 controls were included in this study performed at eight University Hospitals in Spain. None had family history of pituitary adenomas or other endocrine tumors. All patients failed to respond to conventional treatment including surgery and somatostatin analogues. Some patients received adjuvant radiotherapy and most cases required pegvisomant (PEG) treatment for normalisation of IGF1. AIP analysis was performed in DNA extracted from peripheral leucocytes, using standardised PCR protocol in which the coding regions of exons 1, 2, 3, 4, 5 and 6 were amplified. Possible deletions/duplications were studied using multiplex ligation-dependent probe amplification. RESULTS: SEQUENCE CHANGES OF POTENTIAL DIFFERENT SIGNIFICANCE THAT COULD BE CONSIDERED AS MUTATIONS OR VARIATIONS OF UNKNOWN SIGNIFICANCE (VUS) OF THE AIP GENE WERE FOUND IN FOUR PATIENTS (8%). IN TWO CASES, TWO DIFFERENT MUTATIONS PREVIOUSLY DESCRIBED WERE FOUND: p.Arg9Gln and p.Phe269Phe. Two other VUS were also found: c.787+24C>T in intron 5 and c.100-18C>T in intron 1. Age at diagnosis ranged from 21 to 50 years old, and in all patients, the tumor was a macroadenoma depicting IGF1 normalisation under PEG treatment. CONCLUSIONS: AIP germline mutations show a low, but non-negligible, prevalence in non-familial acromegaly patients with tumors resistant to treatment with somatostatin analogues.


Assuntos
Acromegalia/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Adenoma/genética , Adulto , Idoso , Resistencia a Medicamentos Antineoplásicos , Feminino , Mutação em Linhagem Germinativa , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
8.
Clin Endocrinol (Oxf) ; 77(2): 275-80, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22288503

RESUMO

BACKGROUND: An association between treatment for Parkinson's disease with certain dopaminergic drugs and development of cardiac valve impairment has been reported. Recent studies in hyperprolactinaemic patients treated with cabergoline (CAB) have shown either no significant findings or mild tricuspid regurgitation. OBJECTIVE: To determine the prevalence of cardiac valve dysfunction in patients with hyperprolactinaemic conditions chronically treated with CAB or bromocriptine (BR). DESIGN: Retrospective, multicentric, cross-sectional study of cases vs controls. PATIENTS: Eighty-three hyperprolactinaemic patients (15 men, 68 women aged 16·7-63 years; 64% microprolactinomas, 28% macroprolactinomas and 8% other etiologies) from three Spanish university hospitals chronically treated with BR (14-562·5 weeks, cumulative dose 5603 ± 7729 mg) or CAB (12-765 weeks, 217·4 ± 306·6 mg). MEASUREMENTS: Transthoracic echocardiographic assessment of valvular regurgitation and thickening, mitral valve tenting area and left-ventricular ejection fraction from 83 patients were compared with results from 58 age- and sex-matched controls and correlated with cumulative doses of dopaminergic drugs. RESULTS: No significant differences in valvular regurgitation, valve thickness or any other echocardiographic parameter were observed between controls and patients, except for 15 patients in the higher quartile of CAB cumulative dose (>180 mg), with increased prevalence of mild tricuspid regurgitation (6/15, 40% vs 8/58, 13·8%, P = 0·024; OR 4·1; 1·1-14·9). High BR cumulative dose was associated with no significant findings. CONCLUSIONS: No increased valvular involvement was found after long-term dopaminergic therapy for hyperprolactinaemia except for a significant increase in mild tricuspid regurgitation associated with high cumulative doses of CAB; BR seems spared from this adverse effect, although the low number of cases limits this analysis. Cumulative dose registry and long-term studies are warranted to definitely clarify this item.


Assuntos
Antineoplásicos/uso terapêutico , Ergolinas/efeitos adversos , Ergolinas/uso terapêutico , Prolactinoma/tratamento farmacológico , Insuficiência da Valva Tricúspide/induzido quimicamente , Adolescente , Adulto , Bromocriptina/efeitos adversos , Bromocriptina/uso terapêutico , Cabergolina , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
An R Acad Nac Med (Madr) ; 128(1): 49-68, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-23350337

RESUMO

A research on lesions apparently tumorous that appear on jawbones and are not exactly tumors is developed. These lesions are clinically silent, although they produce deformity and, perhaps because of that, an early diagnosis with biopsy or other procedures is needed. The image research can be very characteristic or otherwise, it can be very complex, non specific and not provide everything expected to make the diagnosis. The difference between radiolucent and radiopaque images that produce the querubism-fibrous displasia, prove both extremes in which the diagnosis judgment made by image can or cannot be significant. We have to highlight the presence of giant cells with an osteoclastic nature in most of these pseudo tumorous lesions.


Assuntos
Doenças Maxilares/patologia , Cistos Ósseos Aneurismáticos/patologia , Querubismo/patologia , Fibroma Ossificante/patologia , Displasia Fibrosa Óssea/patologia , Células Gigantes , Humanos , Neoplasias Maxilares/patologia
10.
J Clin Endocrinol Metab ; 95(5): 2147-54, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20207827

RESUMO

CONTEXT: Pegvisomant (PEG) therapy has been associated with drug-induced liver dysfunction in acromegalic patients. The mechanism of its toxicity remains unknown. OBJECTIVE: The primary objective was to determine whether or not the UGT1A1*28 polymorphism associated with Gilbert's syndrome influences the development of liver dysfunction during PEG treatment. DESIGN AND SETTING: A cross-sectional study was conducted in four Spanish university hospitals. PATIENTS: Thirty-six acromegalic patients with active disease, resistant to somatostatin analogs, participated. RESULTS: The prevalence of the UGT1A1*28 homozygous and heterozygous genotypes in acromegalic patients was 14 and 44%, respectively. Ten patients (28%) developed liver function test (LFT) abnormalities. There was a tendency for more frequent liver function abnormalities in males (70% males vs. 30% females, P = 0.058). Carriers of the UGT1A1*28 polymorphism had a higher incidence of LFT abnormalities than the UGT1A1 wild type (43% carriers vs. 7% wild type, P = 0.024). This difference persisted when adjusted in an all-factors multiple regression analysis [coefficient of determination (R(2)) = 0.463; P = 0.008] for age, gender, alcohol consumption, and UGT1A1*28 polymorphism. A stepwise multivariate likelihood binary logistic regression analysis (R(2) = 0.40; P = 0.003) identified male gender (beta = 7.21; P = 0.033) and UGT1A1*28 polymorphism (beta = 14.1; P = 0.028) as the only significant predictors for the development of LFT abnormalities. CONCLUSIONS: The UGT1A1*28 genotype and male gender predict an increased incidence of LFT abnormalities during PEG therapy in acromegaly.


Assuntos
Acromegalia/genética , Doença de Gilbert/tratamento farmacológico , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Hormônio do Crescimento Humano/análogos & derivados , Hepatopatias/tratamento farmacológico , Acromegalia/tratamento farmacológico , Acromegalia/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/genética , Primers do DNA , Feminino , Triagem de Portadores Genéticos , Genótipo , Doença de Gilbert/complicações , Homozigoto , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Receptores da Somatotropina/antagonistas & inibidores , Análise de Regressão , Caracteres Sexuais , TATA Box/genética
11.
J Clin Endocrinol Metab ; 95(1): 222-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19850678

RESUMO

CONTEXT: The deletion of exon 3 in the GH receptor (GHR) has been associated with a different biochemical picture and response to therapy in acromegaly. OBJECTIVE: The aim of the study was to determine whether or not the GHR genotype influences the efficacy of pegvisomant treatment. DESIGN AND SETTING: A cross-sectional study was conducted in six Spanish university hospitals. PATIENTS: Forty-four acromegalic patients with active disease and resistance to somatostatin analogs participated in the study. RESULTS: The prevalence of the full-length GHR and the exon 3-deleted GHR homozygous and heterozygous genotypes was 41, 2, and 57%, respectively. There were no differences in IGF-I or GH pre-pegvisomant levels related to GHR genotype. The exon 3-deleted patients required approximately 20% lower doses of pegvisomant per kilogram of weight (28 +/- 11 compared to 22 +/- 7 mg per kg of weight; P = 0.033) to normalize IGF-I. A stepwise multivariate linear regression analysis (R(2) = 0.27; P = 0.003) identified male gender (beta = -0.79; P = 0.03) and d3-GHR genotype (beta = -0.64; P = 0.007) as the only significant predictors of the dose of pegvisomant per kilogram of weight. In addition, d3-GHR carriers required fewer months for IGF-I normalization (P < 0.01). A stepwise multivariate linear regression analysis (R(2) = 0.40; P = 0.001) revealed that the only significant predictor of the time to IGF-I normalization was the dose of pegvisomant per kilogram of weight (beta = 0.451; P = 0.001). CONCLUSIONS: The exon 3 deletion in the GHR predicts an improved response to pegvisomant therapy in acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/genética , Resistência a Medicamentos/genética , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/genética , Acromegalia/diagnóstico , Adulto , Idoso , Estudos Transversais , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Éxons , Feminino , Genótipo , Antagonistas de Hormônios/uso terapêutico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/fisiologia , Prognóstico , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/fisiologia , Estudos Retrospectivos , Deleção de Sequência/fisiologia , Resultado do Tratamento
12.
Eur J Endocrinol ; 160(4): 535-42, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19147599

RESUMO

CONTEXT: Pegvisomant is an effective treatment for somatostatin analogue-resistant acromegaly, but the determinants defining the response to this treatment are largely unknown. OBJECTIVE: To investigate the efficacy of pegvisomant treatment in resistant acromegalic patients (e.g. serum IGF1 at least 1.25 x upper normal limit) in a clinical setting and the factors conditioning this response. DESIGN AND SETTING: A retrospective cross-sectional study performed in six Spanish University hospitals from 2004 to 2007. Patients Forty-four acromegalic patients (61.4% female, mean age: 49+/-14), 95% of whom had undergone pituitary surgery and 61% having received pituitary radiotherapy. The mean follow-up was 22.7+/-11.2 months. Main outcome measures IGF1 levels reflected treatment efficacy, and the influence of gender, age, weight, previous radiotherapy and duration of treatment was assessed. RESULTS: IGF1 normalisation was achieved in 84% of the patients. Male gender (P<0.05), previous irradiation (P<0.05) and the treatment duration (r=0.364, P<0.02) were associated with a better response to pegvisomant therapy. There was a significant decrease in HbA1c (P<0.001) and in the mean insulin dose (P<0.01) in acromegalic diabetic patients. Although 25% of patients experienced mild adverse events, pegvisomant was only withdrawn in four patients due to side effects (two cases of tumour growth, one liver dysfunction and one headache). CONCLUSIONS: Long-term pegvisomant is a very effective therapy in resistant acromegaly. Male gender and prior radiotherapy influence the therapeutic response rate.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/radioterapia , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/antagonistas & inibidores , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Adolescente , Adulto , Idoso , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Resistência a Medicamentos , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Caracteres Sexuais , Adulto Jovem
14.
Clin Endocrinol (Oxf) ; 68(6): 942-50, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17980002

RESUMO

BACKGROUND: IGF-I is a useful tool in GH disorders diagnosis, however, the use of commercially available kits needs to be validated. OBJECTIVE: To validate the use of serum IGF-I concentrations measured by four immunoassays in the diagnosis of adult GH deficiency and acromegaly. DESIGN: Cross-sectional study. PATIENTS: Fifty GH-deficient (GHD) patients, 41 acromegaly patients and 405 controls. MEASUREMENTS: Serum IGF-I concentrations were measured by four commercial immunoassays: (1) RIA-NICHOLS; (2) ICMA-IMMULITE; (3) IRMA-IMMUNOTECH; and (4) non-extraction-IRMA-DSL. Reference values were established from the control population in six age groups. Individual results were transformed to standard deviation score (SD score) from the age-related reference population and reference data provided by each assay manufacturer. Diagnostic sensitivity for GH deficiency was calculated. RESULTS: IGF-I measured by the four assays differed significantly. In controls, assay 2 yielded the lowest results, followed by assays 1, 3 and 4 (P < 0.0001 for all comparisons). IGF-I declined with age, but no sex-related differences were observed. When IGF-I was standardized with respect to reference data obtained from the manufacturers, it showed better sensitivity in assays 1 and 2, than with our controls (65%vs. 77.5% and 58%vs. 70%, respectively) for GHD diagnosis. With assays 3 and 4, higher sensitivity was obtained when standardized with our controls (62%vs. 52% and 56%vs. 36%, respectively). In acromegaly, IGF-I was > 2 SD score with all assays. CONCLUSIONS: IGF-I SD score for GHD diagnosis differed according to the normative data used. All assays proved to be useful for active acromegaly diagnosis.


Assuntos
Acromegalia/sangue , Hormônio do Crescimento Humano/deficiência , Imunoensaio/métodos , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/metabolismo , Adolescente , Adulto , Distribuição por Idade , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Caracteres Sexuais , Adulto Jovem
15.
An R Acad Nac Med (Madr) ; 125(3): 445-65; discussion 466-71, 2008.
Artigo em Espanhol | MEDLINE | ID: mdl-19505002

RESUMO

We have studied malign tumours of major and minor salivary glands, analyzing the possible etiologic factors in relation to their glandular histological structure (specially in parotid). Classifications have been reviewed, personal in 1971, Armed Forces Institute of Pathology in 1974 and the current one proposed by International Agency for Research on Cancer in 2004. Finally, we analyzed new typified tumours also the tumours with variable biological and clinical behaviour.


Assuntos
Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/etiologia , Neoplasias Parotídeas/patologia
17.
Endocrinol Nutr ; 55(4): 188-9, 2008 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-22975458
18.
J Neurosurg ; 101(1 Suppl): 116-21, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16206983

RESUMO

Malignant prolactinomas, as with other pituitary carcinomas, are rare tumors. The authors describe a 14-year-old boy who presented with visual loss caused by a pituitary prolactinoma. He underwent transsphenoidal surgery, radiotherapy, and dopamine agonist therapy, but 6 years after the initial diagnosis his pituitary tumor regrew and bone and pulmonary metastases developed. The authors review the literature and discuss the clinical presentation of malignant prolactinomas, their rarity, histological characteristics, distribution of the metastases, different treatment approaches, and their poor prognosis.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Hipofisárias/patologia , Prolactinoma/secundário , Adolescente , Agonistas de Dopamina/uso terapêutico , Humanos , Masculino , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Prognóstico , Prolactinoma/radioterapia , Prolactinoma/cirurgia , Transtornos da Visão/etiologia
19.
Clin Endocrinol (Oxf) ; 58(4): 471-81, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12641631

RESUMO

OBJECTIVE: The objective of this open study of 104 patients was to determine whether the somatostatin analogue lanreotide shrinks GH-secreting adenomas and to identify the predictive factors of a significant tumour volume reduction (> 20%). PATIENTS: A total of 104 previously untreated and newly diagnosed acromegalic patients received the prolonged release (PR) formulation of lanreotide (lanreotide 30 mg, one intramuscular injection every 10 days) for either 1 (n = 84), 2 (n = 13), or 3 or more (n = 7) months before transsphenoidal surgery. MEASUREMENTS: Pituitary tumour volumes, tumour extension grade and possible cavernous sinus invasion were assessed in blinded conditions by a centralized team of radiologists. Factors such as demographics, tumour characteristics, GH and IGF-I levels were evaluated as possible predictive factors of a significant tumour volume reduction. The clinical activity and random GH, IGF-I, IGFBP-3, PRL, TSH, free T4 and lanreotide levels serum concentrations were measured under basal conditions and in the 10 days before surgery. All analyses were done in a centralized laboratory. The tolerability of preoperative PR lanreotide and the surgical outcome at the 6th month after surgery were assessed. RESULTS: The presurgical treatment improved the symptoms of acromegaly and induced a statistically significant reduction of GH, IGF-I and IGFBP-3. Despite the short duration of the preoperative lanreotide 30 mg treatment, IGF-I levels were normalized in 25% of patients. A statistically significant reduction in tumour volume (P < 0.001) was observed. The median value of the differences was -152 mm3. A reduction in tumour volume was observed in 66% of patients and was > 20% in 29% of all patients included. Both the univariate analyses and the logistic regression model demonstrated that a positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of a significant tumour shrinkage (odds ratio of 7.8, 95% confidence interval 1.6-37.1). Preoperative PR lanreotide did not modify the expected soft consistence of the tumour. The main adverse events consisted of minor gastrointestinal problems. Univariate analyses revealed that younger age, higher GH and IGF-I levels at diagnosis, higher preoperative tumour volume, more than one tumour extrasellar extension and the presence of cavernous sinus invasion were statistically significant determinants of persistent disease at the 6th month after surgery. The multivariate analysis revealed that higher IGF-I levels at diagnosis and the preoperative cavernous sinus invasion were each statistically significant prognostic factors of persistent disease. CONCLUSIONS: A short administration of preoperative lanreotide 30 mg induced a statistically significant shrinkage of GH-secreting pituitary adenomas where this reduction was > 20% of the pretreatment value in 29% of the whole population. Among the factors considered was the fact that positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of this significant tumour volume reduction.


Assuntos
Adenoma/metabolismo , Antineoplásicos/uso terapêutico , Hormônio do Crescimento/metabolismo , Peptídeos Cíclicos/uso terapêutico , Neoplasias Hipofisárias/metabolismo , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Adenoma/tratamento farmacológico , Adenoma/cirurgia , Adulto , Biomarcadores Tumorais/sangue , Terapia Combinada , Feminino , Hormônio do Crescimento/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Estudos Prospectivos , Resultado do Tratamento
20.
Eur J Endocrinol ; 146(2): 237-40, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11834434

RESUMO

OBJECTIVE: ACTH-independent macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered the treatment of choice, but the patient is obliged to receive lifetime steroid replacement therapy and is susceptible to adrenal insufficiency crisis. New therapeutic alternatives are being proposed as new etiopathological features of the disease are known. Unilateral adrenalectomy of the largest gland can be a safe and effective alternative, but only short-term follow-up is reported in the literature. We present four consecutive patients with ACTH-independent macronodular hyperplasia and long-term remission of Cushing's syndrome after unilateral adrenalectomy. SUBJECTS: Four consecutive patients (two males and two females, mean age 50.3 years) with Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia underwent unilateral adrenalectomy of the largest gland. RESULTS: The weight of the resected glands ranged from 26.8 to 210 g. Two patients suffered transient post-surgical adrenal insufficiency and had steroid replacement therapy for 60 and 14 months respectively. After a mean follow-up of 78.8 months (range 30-137 months) all the patients persist without any evidence of Cushing's syndrome. Urinary free cortisol and serum cortisol, after the adrenal insufficiency stage, have always stayed within their normal ranges, but cortisol circadian rhythm and suppressibility after dexamethasone have never normalized. No further enlargement of the contralateral gland has been documented 62 to 126 months after surgery in three of the four patients. CONCLUSIONS: Unilateral adrenalectomy can be an effective and safe alternative treatment for ACTH-independent macronodular adrenal hyperplasia, and can achieve long-term remission of Cushing's syndrome.


Assuntos
Glândulas Suprarrenais/patologia , Adrenalectomia , Hormônio Adrenocorticotrópico/sangue , Ritmo Circadiano , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Feminino , Seguimentos , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Hiperplasia , Masculino , Pessoa de Meia-Idade , Indução de Remissão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA