DELMAR MUNIZ LOURENCO JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1(2012) LOURENCO JR., Delmar M.; COUTINHO, Flavia L.; TOLEDO, Rodrigo A.; GONCALVES, Tatiana Denck; MONTENEGRO, Fabio L. M.; TOLEDO, Sergio P. A.Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/ multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/ multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/ multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1-related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/ multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/ multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/ multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.
- Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1(2012) COUTINHO, Flavia L.; LOURENCO JR., Delmar M.; TOLEDO, Rodrigo A.; MONTENEGRO, Fabio L. M.; TOLEDO, Sergio P. A.The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.
- Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil(2012) TOLEDO, Rodrigo A.; SEKIYA, Tomoko; LONGUINI, Viviane C.; COUTINHO, Flavia L.; LOURENCO JR., Delmar M.; TOLEDO, Sergio P. A.The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical follow-up); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine.
- Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations(2014) LONGUINI, Viviane C.; LOURENCO JR., Delmar M.; SEKIYA, Tomoko; MEIRELLES, Osorio; GONCALVES, Tatiana D.; COUTINHO, Flavia L.; FRANCISCO, Guilherme; OSAKI, Luciana H.; CHAMMAS, Roger; ALVES, Venancio A. F.; SIQUEIRA, Sheila A. C.; SCHLESINGER, David; NASLAVSKY, Michel S.; ZATZ, Mayana; DUARTE, Yeda A. O.; LEBRAO, Maria Lucia; GAMA, Patricia; LEE, Misu; MOLATORE, Sara; PEREIRA, Maria Adelaide A.; JALLAD, Raquel S.; BRONSTEIN, Marcello D.; CUNHA-NETO, Malebranche B.; LIBERMAN, Bernardo; FRAGOSO, Maria Candida B. V.; TOLEDO, Sergio P. A.; PELLEGATA, Natalia S.; TOLEDO, Rodrigo A.Objective: To date, no evidence of robust genotype-phenotype correlation or disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has been described, leaving the highly variable clinical presentation of patients unaccounted for. Design: As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of 100 patients carrying germline MEN1 gene mutations and 855 population-matched control individuals. Methods: Genotyping of the coding p27 c.326T>G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% CIs using logistic regression. Results: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR=2.55, P=0.019, CI=1.013-5.76). Among patients who are >= 30 years old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (three to four glands affected vs one to two glands affected; OR=18.33; P=0.002, CI=2.88-16.41). This finding remained significant after the Bonferroni's multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, and enteropancreatic and adrenocortical tumors. Conclusions: Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease.
- Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center(2012) MONTENEGRO, Fabio Luiz de Menezes; LOURENCO JUNIOR, Delmar Muniz; TAVARES, Marcos Roberto; ARAP, Sergio Samir; NASCIMENTO JUNIOR, Climerio Pereira; MASSONI NETO, Ledo Mazzei; D'ALESSANDRO, Andre; TOLEDO, Rodrigo Almeida; COUTINHO, Flavia Lima; BRANDAO, Lenine Garcia; SILVA FILHO, Gilberto de Britto e; CORDEIRO, Anoi Castro; TOLEDO, Sergio Pereira AlmeidaMost cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.