Investigation of new genetic, clinical and pathological aspects of endocrine arterial hypertension

• Grant number: 19/15873-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: August 01, 2021
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Madson Queiroz Almeida
• Grantee: Madson Queiroz Almeida
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Pesquisadores principais: Maria Candida Barisson Villares Fragoso
• Associated researchers: Ana Amélia Fialho de Oliveira Hoff ; Ana Claudia Latronico Xavier ; Antonio Marcondes Lerario ; Berenice Bilharinho de Mendonça ; Luciano Ferreira Drager ; Luiz Aparecido Bortolotto ; Maria Cláudia Nogueira Zerbini ; Philippe LORY
• Associated scholarship(s): 24/16029-2 - Functional Investigation of the Pathogenicity of Allelic Variants in New Candidate Genes for the Molecular Pathogenesis of Pheochromocytomas/ Paragangliomas and Primary Hyperaldosteronism, BP.TT; 24/18510-0 - Functional evaluation of germline variants in the phosphodiesterase 2A (PDE2A) and 3A (PDE3A) genes in bilateral primary aldosteronism., BP.DD; 24/16730-2 - Investigation of Somatic Pathogenic Variants in the Telomerase Reverse Transcriptase (TERT) Gene Promoter in Pheochromocytomas and Paragangliomas, BP.IC; + associated scholarships 24/14041-5 - Association of calcium, aldosterone and renine biochemistry with subclinical and clinical atherosclerosis: cross-sectional analysis of the Longitudinal Study for Adult Health (ELSA-Brasil), BP.IC; 24/03610-9 - Investigation of pathogenic variants in KCNJ5, ATP1A1, ATP2B3 and CTNNB1 genes in aldosteronomas., BP.TT; 23/02222-2 - Genetic investigation and genotype-phenotype correlation in the von-Hippel Lindau disease, BP.IC; 22/08560-4 - Assessment of the penetrance of mutations/deletions in the SDHB and SDHD genes, BP.IC; 22/09278-0 - Clinical-hormonal-radiological and genetic characterization of patients with Primary Pigmentary Nodular Adrenocortical Disease (PPNAD) associated or not with Carney Complex, BP.DD; 21/10363-0 - Whole exome sequencing for investigation of novel genetic causes of primary Aldosteronism caused by bilateral adrenal hyperplasia, BP.PD; 21/13269-4 - Investigation of germline pathogenic variants in SDHB, SDHD, SDHC, TMEM127 and MAX genes in individuals with pheochromocytomas and paragangliomas, BP.TT; 21/11240-9 - Whole exome sequencing for the investigation of novel genetic causes of metastatic Pheochromocytomas and Paragangliomas, BP.PD; 21/10101-5 - Investigation of novel genetic alterations associated with the pathogenesis of Aldosteronomas by exome sequencing, BP.DD; 21/09879-1 - Clinical and genetic investigation of the association between Primary Aldosteronism and Papillary Thyroid Cancer, BP.DD - associated scholarships

Abstract

Arterial hypertension (AH) is an important cardiovascular risk factor, with an estimated prevalence of 10 to 40% of adults in developed countries. AH is primary or essential in the majority of the cases, but the prevalence of secondary AH increases to around 30% in young adults. Among patients with resistant AH, screening for primary aldosteronism (PA) and for catecholamine-secreting tumors (pheochromocytomas and paragangliomas - PPGLs) is recommended. PA represents the most frequent cause of endocrine AH, with a prevalence of 20% among individuals with resistant AH. In this thematic proposal, we will investigate new genetic, clinical and anatomopathological aspects of endocrine AH. The specific aims of this project are: 1) To investigate new genetic causes of PA using massive parallel sequencing (MPS); 2) To evaluate the efficacy of the oral furosemide test as a new diagnostic tool for PA; 3) To define new anatomopathological criteria to characterize adrenal lesions associated with PA; 4) To investigate clinical and genetic aspects of the association between PA and thyroid cancer (a new endocrine tumor syndrome?); 5) To investigate new genetic etiologies of PPGLs using MPS; 6) To conduct a clinical randomized study to evaluate predictive features of cardiovascular risk in patients with adrenal incidentaloma and autonomous cortisol secretion. To conduct these projects, we have a multidisciplinary team with expertise in endocrine AH from the fields of endocrinology, cardiology, nephrology, pathology and bioinformatics. As expected outcomes, we will increase the knowledge about molecular pathogenesis, clinical and anomopathological diagnosis of endocrine AH, expanding the available tools for the diagnosis and management of patients in clinical practice. In addition, our findings will build a solid platform for genetic, clinical and anatomopathological data about endocrine AH with relevant impact on clinical and academic levels. (AU)

Scientific publications

(17)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHEI, A. A. W.; FREITAS, T. C.; FAGUNDES, G. F. C.; PETENUCI, J.; VILELA, L. A. P.; BRITO, L. P.; GOLDBAUM, T. S.; ZERBINI, M. C. N.; LEDESMA, F. L.; YANNO, F. Y.; et al. Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening (Nov, dgac679, 2022). JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 1-pg., 2023-01-23. (19/15873-6, 21/09879-1)

FAGUNDES, GUSTAVO F. C.; ALMEIDA, MADSON Q.. erioperative Management of Pheochromocytomas and Sympathetic Paraganglioma. JOURNAL OF THE ENDOCRINE SOCIETY, v. 6, n. 2, FEB 1 2022. (19/15873-6)

FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; AFONSO, ANA CAROLINE F.; PETENUCI, JANAINA; FUNARI, MARIANA F. A.; GUIMARAES, AUGUSTO G.; LEDESMA, FELIPE L.; PEREIRA, MARIA ADELAIDE A.; VICTOR, CAROLINA R.; et al. Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 10-pg., 2023-01-18. (19/15873-6, 21/10101-5, 21/11240-9, 21/10363-0)

MACIEL, ANA ALICE W.; DANILOVIC, DEBORA L. S.; SOARES, IBERE C.; FREITAS, THAIS C.; OKUBO, JESSICA; FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; GUIMARAES, AUGUSTO G.; CALSAVARA, VINICIUS F.; et al. Association Between Papillary Thyroid Cancer and Primary Aldosteronism in Individuals With Hypertension. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 12-pg., 2024-09-30. (21/10101-5, 21/11240-9, 21/10363-0, 19/15873-6, 21/09879-1)

OKUBO, JESSICA; FRUDIT, PAULA; CAVALCANTE, ALINE C. B. S.; MACIEL, ANA A. W.; FREITAS, THAIS C.; PILAN, BRUNA; FAGUNDES, GUSTAVO F. C.; QUEIROZ, NARA L.; STUMPF, MATHEO A. M.; SOUZA, VICTOR C. M.; et al. Contralateral Suppression in Adrenal Venous Sampling Predicts Clinical and Biochemical Outcome in Primary Aldosteronism. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 109, n. 9, p. 12-pg., 2024-03-05. (19/15873-6, 21/09879-1)

FREITAS, THAIS C.; MACIEL, ANA ALICE W.; FAGUNDES, GUSTAVO F. C.; PETENUCI, JANAINA; SANTANA, LUCAS S.; GUIMARAES, AUGUSTO G.; FREITAS-CASTRO, FELIPE; SROUGI, VICTOR; TANNO, FABIO Y.; CHAMBO, JOSE L.; et al. Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis. JOURNAL OF THE ENDOCRINE SOCIETY, v. 8, n. 1, p. 10-pg., 2023-12-01. (21/10101-5, 21/11240-9, 21/10363-0, 19/15873-6, 21/09879-1)

FREITAS-CASTRO, FELIPE; ALMEIDA, MADSON Q.. Personalized management for phaeochromocytomas and paragangliomas in Latin America: A genetic perspective. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, v. 39, n. 1, p. 8-pg., 2025-01-01. (19/15873-6, 21/11240-9)

FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; FAGUNDES, GUSTAVO F. C.; LOBATO, EDUARDO C.; AFONSO, ANA CAROLINE F.; NAKAMURA, IZABEL T.; LEDESMA, FELIPE L.; SOARES, IBERE C.; MENDONCA, BERENICE B.; LATRONICO, ANA CLAUDIA; et al. SLC25A11, a Novel Gene Associated With Carney-Stratakis Syndrome. JOURNAL OF THE ENDOCRINE SOCIETY, v. 9, n. 5, p. 9-pg., 2025-05-01. (19/15873-6, 21/10363-0, 24/03610-9, 21/11240-9)

LAGANA, MARTA; HABRA, MOUHAMMED AMIR; REMDE, HANNA; ALMEIDA, MADSON Q.; COSENTINI, DEBORAH; PUSCEDDU, SARA; GRANA, CHIARA MARIA; CORSSMIT, ELEONORA P. M.; BONGIOVANNI, ALBERTO; DE FILPO, GIUSEPPINA; et al. Adverse skeletal related events in patients with bone-metastatic pheochromocytoma/paraganglioma. EUROPEAN JOURNAL OF CANCER, v. 208, p. 7-pg., 2024-07-23. (19/15873-6)

FAGUNDES, GUSTAVO F. C.; FREITAS-CASTRO, FELIPE; SANTANA, LUCAS S.; LEDESMA, FELIPE L.; PETENUCI, JANAINA; AFONSO, ANA CAROLINE F.; PEREIRA, CAIO A. A.; MACIEL, ANA ALICE W.; SOARES, IBERE C.; GOMES, NATHALIA L.; et al. Insights into the genetic landscape of pheochromocytomas and paragangliomas in a Brazilian cohort. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 192, n. 1, p. 14-pg., 2025-01-06. (19/15873-6, 21/10363-0, 21/11240-9, 21/09879-1)

MORI, GUSTAVO H.; FAGUNDES, GUSTAVO F. C.; SANTANA, LUCAS S.; FREITAS-CASTRO, FELIPE; AFONSO, ANA CAROLINE F.; LOURENCO, DELMAR M.; PEREIRA, MARIA ADELAIDE A.; TANNO, FABIO Y.; SROUGI, VICTOR; CHAMBO, JOSE L.; et al. Pathogenicity of germline VHL variants is associated with renal cell carcinoma size in von Hippel-Lindau disease. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 69, p. 6-pg., 2025-01-01. (19/15873-6, 21/10363-0, 21/11240-9)

KAWAHARA, EDUARDO Z.; OKUBO, JESSICA; CAVALCANTE, ALINE C. B. S.; PILAN, BRUNA; FRUDIT, PAULA; PEREIRA, CAIO A. A.; BASMAGE, LARISSA; VIEL, JACQUELINE M.; MACIEL, ANA ALICE W.; FREITAS, THAIS C.; et al. Adrenal Venous Sampling Using Metanephrine in Primary Aldosteronism With or Without Cortisol Cosecretion. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 9-pg., 2025-01-07. (19/15873-6, 21/09879-1)

FAGUNDES, GUSTAVO F. C.; ALMEIDA, MADSON Q.. Pitfalls in the Diagnostic Evaluation of Pheochromocytomas. JOURNAL OF THE ENDOCRINE SOCIETY, v. 8, n. 6, p. 12-pg., 2024-04-06. (19/15873-6)

MAGALHAES, ISABELLE P. A.; BOGER, BIBIANA D.; GOMES, NATHALIA L.; MARTINS, GUILHERME L. P.; BOMFIM, LEOMARQUES A.; FAGUNDES, GUSTAVO F. C.; ROCHA, ROBERTA S.; COELHO, FERNANDO M. A.; CHAMBO, JOSE L.; LATRONICO, ANA CLAUDIA; et al. Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report. FRONTIERS IN ENDOCRINOLOGY, v. 15, p. 5-pg., 2024-04-15. (19/15873-6)

QUEIROZ, NARA L.; STUMPF, MATHEO A. M.; SOUZA, VICTOR C. M.; MACIEL, ANA ALICE W.; FAGUNDES, GUSTAVO F. C.; OKUBO, JESSICA; SROUGI, VICTOR; TANNO, FABIO Y.; CHAMBO, JOSE L.; PEREIRA, MARIA ADELAIDE A.; et al. Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism. Hormone and Metabolic Research, v. 56, n. 05, p. 8-pg., 2024-01-22. (19/15873-6)

MACIEL, ANA ALICE W.; FREITAS, THAIS C.; FAGUNDES, GUSTAVO F. C.; PETENUCI, JANAINA; VILELA, LETICIA A. P.; BRITO, LUCIANA P.; GOLDBAUM, TATIANA S.; ZERBINI, MARIA CLAUDIA N.; LEDESMA, FELIPE L.; TANNO, FABIO Y.; et al. Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 11-pg., 2022-11-22. (19/15873-6)

SANTANA, LUCAS S.; GUIMARAES, AUGUSTO G.; ALMEIDA, MADSON Q.. Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome. FRONTIERS IN ENDOCRINOLOGY, v. 13, p. 13-pg., 2022-06-23. (19/15873-6)