Analysis of biomarkers in patients with primary aldosteronism and mild autonomous cortisol secretion

• Grant number: 23/00196-4
• Support Opportunities: Scholarships abroad - Research
• Start date: September 01, 2023
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lívia Mara Mermejo
• Grantee: Lívia Mara Mermejo
• Host Investigator: Adina Florina Turcu
• Host Institution: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Michigan, United States

Abstract

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA has histological heterogeneity and clinical variability. Some patients with PA have increased excretion of cortisol and glucocorticoid metabolites. In a German cohort of PA,77.6% of the patients had a positive result for at least one of three screening tests for Cushing's syndrome. The coexistence of autonomous cortisol secretion is associated with poor clinical outcomes, impaired glucose metabolism, and psychological symptoms. Recently, due to advances in steroid metabolomics, it is possible to differentiate adrenal lesions based on steroid fingerprinting, e.g., the levels of 18-hydroxicortisol and 18-oxocortisol are higher in PA patients than in those with primary hypertension. Immunohistochemical analyses of steroid pathways, such as CYP11B1/CYP11B2, in adrenal tissues can also provide new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between clinical characteristics, steroid profile, enzyme expression and genotype of PA with mild autonomous cortisol excess is still necessary. Objective: To investigate the correlation between clinical characteristics and steroid fingerprinting, steroidogenic enzyme expression, and genotype in PA with and without mild autonomous cortisol excess. Material and methods: This will be a retrospective cross-sectional study. We will include 150 PA patients followed at the University of Michigan stratified into two groups: PA with mild autonomous cortisol excess (n=50) and PA without mild autonomous cortisol excess (n=100), according to 1 mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL). We will use mass spectrometry to quantify a multi-steroid panel from peripheral serum in PA patients. Immunohistochemical labelling of formalin-fixed paraffin-embedded (FFPE) sections will be used to analyze CYP11B1 and CYP11B2 immunostaining. Sequencing analysis of driver genes in PA will be performed. The results of steroid profile, immunostaining, and genotype will be compared between PA with and without mild autonomous cortisol excess. The better understanding of cosecretion physiopathology can help individualize and optimize the treatment of PA patients. (AU)

Scientific publications

(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)

MERMEJO, LIVIA MARA; ZANELLA, RENATO HERON; COCICOV, LARISSA; MOLINA, CARLOS A. FERNANDES; TUCCI JUNIOR, SILVIO; ELIAS JUNIOR, JORGE; MUGLIA, VALDAIR FRANCISCO; VIANI, GUSTAVO ARRUDA; ELIAS, PAULA C. L.; MOREIRA, AYRTON CUSTODIO; et al. Stereotactic radiotherapy as a valuable therapeutic procedure for controlling aldosterone-secreting adrenocortical carcinoma. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 68, p. 6-pg., 2024-01-01. (14/03989-6, 23/00196-4)