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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- Could the Less-Than Subtotal Parathyroidectomy Be an Option for Treating Young Patients With Multiple Endocrine Neoplasia Type 1-Related Hyperparathyroidism?(2019) MONTENEGRO, Fabio Luiz de Menezes; BRESCIA, Manilla D'Elboux Guimaraes; JR, Delmar Muniz Lourenco; ARAP, Sergio Samir; D'ALESSANDRO, Andre Fernandes; SILVA FILHO, Gilberto de Britto e; TOLEDO, Sergio Pereira de AlmeidaBackground: The surgical treatment of primary hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1 (MEN1) has evolved due the concern of permanent hypoparathyroidism. As the diagnosis has increased, the extent of operation has decreased. Most MEN1 patients requiring parathyroidectomy are younger than 50 years and they pose a difficult balance to achieve between persistent HPT and life-long hypoparathyroidism. The aim of the present study is to review our experience with a large series of patients with MEN1-related HPT (HPT/MEN1) treated at a single institution in order to find clues to a better treatment decision in these younger cases. Method: Retrospective analysis of consecutive HPT/MEN1 cases treated at a single institution with different operations: total parathyroidectomy and immediate forearm autograft (TPTX-AG), subtotal (STPTX), unintentional less than subtotal (U-LSTPTX) and intentional less than subtotal parathyroidectomy (I-LSTPTX). Results: Considering 84 initial cases operated on since 2011 (TPTX-AG, 39; STPTX, 22, U-LSTPTX, 13, and I-LSTPTX, 10), the rates of hypoparathyroidism were 30.8% (U-LSTPTX), 28.2% (TPTX-AG), 13.6% (STPTX), and 0% (I-LSTPTX). Two-thirds of them (68%; 57/84) were young (< 50 years) or asdolescents. MIBI scan was more sensitive to show parathyroid glands and bilateral disease. Considering the concordance of MIBI and ultrasound for the possibility of unilateral clearance, it would be suitable to 22.6% of the cases. Intra-operative parathormone showed a significant decay even after unilateral exploration, but longer follow up is necessary. Overall, there were seven (4%) adolescents in 161 cases treated from 1987 to 2018, three underwent TPTX-AG and four had U-LSTPTX. Five are euparathyroid, one had mild recurrence, and one required a reoperation after 8 years due to the residual gland. Conclusions: Young patients are the most frequent candidates to parathyroidectomy. Less extensive procedures may be planned only if carefully reviewed preoperative imaging studies suggest a localized disease. Patients and their relatives should be fully informed of the risks and benefits during consent process. Future research with larger cohorts and long-term results are necessary to clarify if less than I-LSPTX or unilateral clearance are really adequate in selected groups of patients with HPT/MEN1 presenting lower volume of disease detected by preoperative imaging studies.
- Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study(2019) MACIEL, Rui M. B.; CAMACHO, Cleber P.; ASSUMPCAO, Ligia V. M.; BUFALO, Natassia E.; CARVALHO, Andre L.; CARVALHO, Gisah A. de; CASTRONEVES, Luciana A.; JR, Francisco M. de Castro; CEOLIN, Lucieli; CERUTTI, Janete M.; CORBO, Rossana; FERRAZ, Tania M. B. L.; V, Carla Ferreira; FRANCA, M. Inez C.; GALVAO, Henrique C. R.; GERMANO-NETO, Fausto; GRAF, Hans; JORGES, Alexander A. L.; KUNII, Ilda S.; LAURIA, Marcio W.; LEAL, Vera L. G.; LINDSEY, Susan C.; JR, Delmar M. Lourenco; MADER, Lea M. Z.; MAGALHAES, Patricia K. R.; MARTINS, Joao R. M.; MARTINS-COSTA, M. Cecilia; MAZETOR, Glaucia M. F. S.; IMPELLIZZERI, Anelise I.; NOGUEIRA, Celia R.; I, Edenir Palmero; PESSOA, Cencita H. C. N.; PRADA, Bibiana; SIQUEIRA, Debora R.; SOUSA, Maria Sharmila A.; TOLEDO, Rodrigo A.; VALENTE, Flavia O. F.; VAISMAN, Fernanda; WARD, Laura S.; WEBER, Shana S.; V, Rita Weiss; YANG, Ji H.; DIAS-DA-SILVA, Magnus R.; HOFF, Ana O.; TOLEDO, Sergio P. A.; MAIA, Ana L.Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
- Quality of Life and Coping in Multiple Endocrine Neoplasia Type 2(2019) CORREA, Fernanda A.; FARIAS, Evelin C.; CASTRONEVES, Luciana A.; LOURENCO JR., Delmar M.; HOFF, Ana O.Scarce data are available on the quality of life and psychosocial distress of patients with multiple endocrine neoplasia type 2 (MEN2), a genetic cancer syndrome caused by RET germline mutations. Carriers of RET mutations can face several challenges, including fear for the future, guilt for transmission of a germline mutation to an offspring, side effects of cancer treatment, coping behaviors in the face of a chronic and frequently incurable cancer, and difficulties in access to adequate health care. We have addressed the effects of genetic testing on the quality of life of patients with MEN2 and the lifelong physical and psychosocial challenges experienced by these patients. We have also suggested strategies to minimize the burden of living with this chronic condition and the perspectives on future studies to improve the health-related quality of life of the patients.
- Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group(2017) RIECHELMANN, Rachel P.; WESCHENFELDER, Rui F.; COSTA, Frederico P.; ANDRADE, Aline Chaves; OSVALDT, Alessandro Bersch; QUIDUTE, Ana Rosa P.; SANTOS, Allan dos; HOFF, Ana Amelia O.; GUMZ, Brenda; BUCHPIGUEL, Carlos; PEREIRA, Bruno S. Vilhena; LOURENCO JUNIOR, Delmar Muniz; ROCHA FILHO, Duilio Reis da; FONSECA, Eduardo Antunes; MELLO, Eduardo Linhares Riello; MAKDISSI, Fabio Ferrari; WAECHTER, Fabio Luiz; CARNEVALE, Francisco Cesar; COURA-FILHO, George B.; PAULO, Gustavo Andrade de; GIROTTO, Gustavo Colagiovanni; BEZERRA NETO, Joao Evangelista; GLASBERG, Joao; CASALI-DA-ROCHA, Jose Claudio; REGO, Juliana Florinda M.; MEIRELLES, Luciana Rodrigues de; HAJJAR, Ludhmila; MENEZES, Marcos; BRONSTEIN, Marcello D.; SAPIENZA, Marcelo Tatit; FRAGOSO, Maria Candida Barisson Villares; PEREIRA, Maria Adelaide Albergaria; BARROS, Milton; FORONES, Nora Manoukian; AMARAL, Paulo Cezar Galvao do; MEDEIROS, Raphael Salles Scortegagna de; ARAUJO, Raphael L. C.; BEZERRA, Regis Otaviano Franca; PEIXOTO, Renata D'Alpino; AGUIAR JR., Samuel; RIBEIRO JR., Ulysses; PFIFFER, Tulio; HOFF, Paulo M.; COUTINHO, Anelisa K.Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
- New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations(2019) FAGUNDES, Gustavo F. C.; PETENUCI, Janaina; JR, Delmar M. Lourenco; TRARBACH, Ericka B.; PEREIRA, Maria Adelaide A.; D'EUR, Joya Emilie Correa; HOFF, Ana O.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Context: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-yearold boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.
- Editorial: Early Genetic and Clinical Diagnosis in MEN1(2020) LOURENCO JR., Delmar M.; HERDER, Wouter W. de
- Questions and Controversies About Parathyroid Pathophysiology in Children With Multiple Endocrine Neoplasia Type 1(2018) MARX, Stephen J.; LOURENCO JR., Delmar M.
- Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases(2022) ARAUJO, Paula B.; CARVALLO, Mirna S.; VIDAL, Ana P.; NASCIMENTO, Joao B.; WO, Julia M.; NALIATO, Erika O.; NETO, Silvio H. Cunha; CONCEICAO, Flavia L.; FONTES, Rosita; LIMA, Vinicius V. de; CARVALHO, Denise P.; SOARES, Paula; LIMA, Jorge; JR, Delmar M. Lourenco; VIOLANTE, Alice Helena D.Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm x 6.0 cm x 6.0 cm, 6.0 cm x 4.0 cm x 3.2 cm, and 7.5 cm x 6.0 cm x 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.
- Impact of parathyroidectomy on quality of life in multiple endocrine neoplasia type 1(2022) BRESCIA, Marilia D'Elboux Guimaraes; RODRIGUES, Karine Candido; D'ALESSANDRO, Andre Fernandes; ALVES FILHO, Wellington; PLAS, Willemijn Y. van der; KRUIJFF, Schelto; ARAP, Sergio Samir; TOLEDO, Sergio Pereira de Almeida; MONTENEGRO, Fabio Luiz de Menezes; LOURENCO, Delmar MunizBackground: Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown. Method: Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume. Results: Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = -0.60, P = 0.0004) and MCS (r = -0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities. Conclusion: A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.
- Giant Prolactinoma Causing Hydrocephalus and Intracranial Hypertension as First Manifestations of Multiple Endocrine Neoplasia Type 1(2019) DANTAS, Naiara C. B.; SOARES, Carlos E. L.; MARTINS, Manoel R. A.; LOURENCO JR., Delmar M.; QUIDUTE, Ana R. P.Context: Overall, giant prolactinomas are rare tumors (4%), especially those larger than 60 mm (1%). Despite the predominance of macroadenoma documented in multiple endocrine neoplasia type 1 (MEN1)-related prolactinoma, only three giant prolactinoma cases were described so far (size > 40 mm and prolactin > 1,000 ng/mL). None of them was larger than 60 mm or presented hydrocephalus or intracranial hypertension (ICH) as initial manifestation of MEN1. Case Description: A 21-years-old man presented with ICH as the first clinical manifestation of MEN1. He harbored a MEN1 germline mutation but refused periodic vigilance after normal hormonal screening at age 14 years. During investigation, magnetic resonance imaging (MRI) of the skull showed an expansive sellar/parasellar lesion (75 x 44 x 36 mm) with moderate to severe supratentorial obstructive hydrocephalus and an extremely high serum prolactin (PRL) of 10,800 ng/mL, without combined hypersecretion of other pituitary hormones. He was diagnosed with giant prolactinoma, and cabergoline was initiated. The patient evolved with early improvement of clinical complaints for hydrocephalus and ICH and PRL reached normal values (11 ng/mL) in association with significant tumoral shrinkage after 18 months on cabergoline. After 2 months of cabergoline, cerebrospinal fluid leakage was diagnosed and corrective surgery was provided. The mean dose of cabergoline was 3 mg/week throughout treatment. Conclusion: We reported the first case with hydrocephalus and ICH as the initial clinical manifestation of a giant prolactinoma in MEN1. From our knowledge, this is the largest MEN1-related prolactinoma reported so far. Notably, all four MEN1-related giant prolactinomas cases reported were younger than 21 years strengthening the importance to routine MEN1 genetic testing for prolactinoma in this age group. Also, they all had initial effective response with dopamine agonist ensuring this drug as first-line treatment for MEN1-related giant prolactinoma. However, the scarce number of treated patients and progression of cabergoline resistance in two of them suggest strict surveillance.