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      Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis

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          Abstract

          Context

          Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved.

          Objective

          To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis.

          Methods

          We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA.

          Results

          The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test.

          Conclusion

          The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.

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          Most cited references44

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          2018 ESC/ESH Guidelines for the management of arterial hypertension

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            The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

            To develop clinical practice guidelines for the management of patients with primary aldosteronism.
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              A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients.

              We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+ and K+ in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) > or =50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). A total of 1,180 patients (age 46 +/- 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.
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                Author and article information

                Contributors
                Journal
                J Endocr Soc
                J Endocr Soc
                jes
                Journal of the Endocrine Society
                Oxford University Press (US )
                2472-1972
                01 December 2023
                24 November 2023
                24 November 2023
                : 8
                : 1
                : bvad147
                Affiliations
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Unidade de Hipertensão, Disciplina de Nefrologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Unidade de Hipertensão, Instituto do Coração (InCor), Faculdade de Medicna da Universidade de São Paulo , São Paulo, 05403-900, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Oncologia Endócrina, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo , São Paulo, 01246-000, Brazil
                Unidade de Hipertensão, Disciplina de Nefrologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Unidade de Hipertensão, Instituto do Coração (InCor), Faculdade de Medicna da Universidade de São Paulo , São Paulo, 05403-900, Brazil
                Divisão de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Faculdade de Medicina da Universidade de São Paulo , São Paulo, 05403-000, Brazil
                Divisão de Oncologia Endócrina, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo , São Paulo, 01246-000, Brazil
                Author notes
                Correspondence: Madson Q. Almeida, MD, Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas e Instituto do Câncer (ICESP), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 40 andar, Sala 4344, São Paulo, SP, 01246-903, Brazil. Email: madson.a@ 123456hc.fm.usp.br .
                Author information
                https://orcid.org/0000-0001-8346-3833
                https://orcid.org/0000-0003-2557-1355
                https://orcid.org/0000-0002-2957-6148
                Article
                bvad147
                10.1210/jendso/bvad147
                10701630
                38075562
                0555cb78-4ed2-40a6-86d5-7e0e3572b341
                © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 July 2023
                : 20 November 2023
                : 07 December 2023
                Page count
                Pages: 10
                Funding
                Funded by: Sao Paulo Research Foundation, DOI 10.13039/501100001807;
                Award ID: 2019/15873-6
                Funded by: National Council for Scientific and Technological Development (CNPq), DOI 10.13039/501100003593;
                Categories
                Clinical Research Article
                AcademicSubjects/MED00250

                primary aldosteronism,diagnosis,furosemide,confirmatory test

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