MARCELLO DELANO BRONSTEIN
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
27 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 27
- Influence of growth hormone receptor (GHR) exon 3 and-202A/C IGFBP-3 genetic polymorphisms on clinical and biochemical features and therapeutic outcome of patients with acromegaly(2015) JALLAD, Raquel S.; TRARBACH, Ericka B.; DUARTE, Felipe H.; JORGE, Alexander A. L.; BRONSTEIN, Marcello D.The association of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms with clinical presentation, biochemical measurements and response to therapies in acromegaly have been suggested. To evaluate the presence of these polymorphisms in acromegaly and their influence on clinical and laboratorial characteristics of patients at diagnosis and after treatment in a large cohort of acromegalic patients. This is a cross-sectional study developed in a single tertiary reference center. Clinical data were obtained from the medical records of 186 acromegalic patients (116 women, age range 21-88 years). GH and IGF1 levels and GHR-exon 3 and -202 A/C IGFBP3 polymorphisms were evaluated in the same hospital. At diagnosis, serum GH concentrations were lower in patients with GHR-d3 genotype than those with GHR-fl, whereas an association of lower IGFBP3 levels with d3 allele was observed only after neurosurgical or medical treatments. However, these associations were not confirmed in posterior statistical analysis. Our results suggest that GHR-exon 3 and -202 A/C IGFBP3 polymorphisms did not show any consistent association on clinical and laboratorial features of acromegalic patients even after treatment.
- Acromegaly in the elderly patient(2019) JALLAD, Raquel S.; BRONSTEIN, Marcello D.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 correlates inversely with the patient's age, disease duration and last GH level.
- SOCS2 polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients(2017) TRARBACH, Ericka B.; JORGE, Alexander A.; DUARTE, Felipe H.; BRONSTEIN, Marcello D.; JALLAD, Raquel S.Purpose Suppressor of cytokine signaling 2 (SOCS2) is a STAT5b-regulated gene and one of its functions is to influence growth and development through negative regulatory effects on GH/IGF-1 pathway. So, we evaluate the potential influence of SOCS2 single nucleotide polymorphisms (SNPs) on clinical and laboratorial characteristics of a large cohort of Brazilian patients with acromegaly. Methods Four SOCS2 SNPs (rs3782415, rs3816997, rs3825199 and rs11107116) were selected and genotyped by real-time PCR using specific Taqman probe assays. A total of 186 patients (116 women, age range 26-88 years) were evaluated. Results No association of SOCS2 genotypes was observed with none of the following clinical and laboratorial characteristics: age, sex, body mass index, comorbidities, basal GH, oral glucose tolerance test GH nadir, IGF-I, ULNRIGF-I. Conclusion Despite of the key role of SOCS2 in the regulation of GH receptor signaling, we did not find any significant association between SOCS2 polymorphisms and acromegaly.
conferenceObject Impact of Clomiphene Citrate on IGF-1 and Testosterone Levels in Acromegalic Patients Non Controlled By Conventional Therapy(2014) DUARTE, Felipe H. G.; JALLAD, Raquel S.; BRONSTEIN, Marcello D.- Association between KISS1 rs5780218 promoter polymorphism and onset of growth hormone secreting pituitary adenoma(2019) AMORIM, Paulo V. G. H.; GRANDE, Isabella P. P.; BATISTA, Rafael L.; SILVEIRA, Leticia F. G.; FREIRE, Ane Caroline T. B.; BRONSTEIN, Marcello D.; JALLAD, Raquel S.; TRARBACH, Ericka B.Objectives. - This study analyzed the KISS1 c.-145delA (rs5780218) promoter polymorphism in a cohort of patients with growth hormone secreting pituitary adenoma (somatotropinoma) and controls, to investigate its role in the incidence of acromegaly and to assess patient/tumor characteristics. Material and methods rs5780218 allelic and genotypic distributions were compared between 49 somatotropinoma patients and 167 healthy controls. rs5780218 was also assessed in relation to patient characteristics and tumor aggressiveness, as characterized by tumor invasion and resistance to conventional therapy. The relationship between KISS1 mRNA expression and the rs5780218 genotype was also assessed in available pituitary tumor samples. Results. - The homozygous -/- variant genotype was associated with high rates of somatotropinoma (P < 0.01), but not with tumor invasiveness, patient characteristics or hormonal remission. KISS1 mRNA expression was much lower in somatotropinomas carrying the deleted allele than in homozygous wild type AA. Conclusions. - In this pilot study, the rs5780218 promoter polymorphism was evaluated in pituitary adenoma, and showed a possible association with the incidence of somatotropinoma but not with tumor progression.
conferenceObject Dramatic Size Reduction with Primary Pharmacological Therapy of a Giant Pituitary Macroadenoma in an Acromegalic Patient(2014) MIRANDA, Mirela Costa de; NAKAGUMA, Marilena; DUARTE, Felipe H. G.; JALLAD, Raquel S.; BRONSTEIN, Marcello D.- Challenges in the diagnosis and management of acromegaly: a focus on comorbidities(2016) ABREU, Alin; TOVAR, Alejandro Pinzon; CASTELLANOS, Rafael; VALENZUELA, Alex; GIRALDO, Claudia Milena Gomez; PINEDO, Alejandro Castellanos; GUERRERO, Doly Pantoja; BARRERA, Carlos Alfonso Builes; FRANCO, Humberto Ignacio; RIBEIRO-OLIVEIRA JR., Antonio; VILAR, Lucio; JALLAD, Raquel S.; DUARTE, Felipe Gaia; GADELHA, Monica; BOGUSZEWSKI, Cesar Luiz; ABUCHAM, Julio; NAVES, Luciana A.; MUSOLINO, Nina Rosa C.; FARIA, Maria Estela Justamante de; ROSSATO, Ciliana; BRONSTEIN, Marcello D.Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.
article 13 Citação(ões) na Scopus Pregnancy and pituitary adenomas(2016) GLEZER, Andrea; JALLAD, Raquel S.; MACHADO, Marcio C.; FRAGOSO, Maria Candida; BRONSTEIN, Marcello D.Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition.- Differential gene expression of sirtuins between somatotropinomas and nonfunctioning pituitary adenomas(2018) GRANDE, Isabella P. P.; AMORIM, Paulo V. G. H.; FREIRE, Ane Caroline The B.; JALLAD, Raquel S.; MUSOLINO, Nina R.; CESCATO, Valter A.; SILVA, Gilberto O. da; BRONSTEIN, Marcello D.; TRARBACH, Ericka B.Sirtuins 1-7 (SIRT) are a highly conserved family of histone deacetylases involved in the regulation of longevity that have a considerable impact in transcription, DNA repair regulation, telomeric stability, cell senescence and apoptosis. In the present study, SIRT1-7 mRNA levels were evaluated in 37 somatotropinomas and 31 nonfunctioning pituitary adenomas (NFPAs) using qPCR and relation to tumor size, invasiveness and Ki-67 proliferative index was made. Overexpression of SIRT1 was observed in 86.5% of somatotropinomas versus 41.9% of NFPAs (P < 0.01). SIRT3 was more underexpressed in NFPAs than somatotropinomas (77.4 and 40.5%, respectively, P < 0.01) as well as SIRT4 and SIRT7. Despite the lack of association between sirtuins and invasiveness or Ki-67 index, SIRT1 and SIRT3 expressions were related to tumor size. Mean of the largest diameter was smaller in adenomas with SIRT1 overexpression than with normal expression (P < 0.01) and SIRT3 underexpression was associated with larger tumors (P < 0.01). In conclusion, a pronounced difference in sirtuins expression was identified between pituitary adenomas, suggesting that these genes are potential markers of pituitary adenomas and could be employed in the characterization of somatotropinomas and NFPAs. The role of sirtuins in pathogenesis of pituitary tumors merits further investigation and possibly will provide new molecular insight about their progression.
- Estrogens and selective estrogen receptor modulators in acromegaly(2016) DUARTE, Felipe H.; JALLAD, Raquel S.; BRONSTEIN, Marcello D.Despite recent advances in acromegaly treatment by surgery, drugs, and radiotherapy, hormonal control is still not achieved by some patients. The impairment of IGF-1 generation by estrogens in growth hormone deficient patients is well known. Patients on oral estrogens need higher growth hormone doses in order to achieve normal IGF-1 values. In the past, estrogens were one of the first drugs used to treat acromegaly. Nevertheless, due to the high doses used and the obvious side effects in male patients, this strategy was sidelined with the development of more specific drugs, as somatostatin receptor ligands and dopamine agonists. In the last 15 years, the antagonist of growth hormone receptor became available, making possible IGF-1 control of the majority of patients on this particular drug. However, due to its high cost, pegvisomant is still not available in many centers around the world. In this setting, the effect of estrogens and also of selective estrogen receptor modulators on IGF-1 control was reviewed, and proved to be an ancillary tool in the management of acromegaly. This review describes data concerning their efficacy and place in the treatment algorithm of acromegaly.
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