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  • 1
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: M.A. Stumpf: None. N.L. Queiroz: None. V.C. Souza: None. A.W. Maciel: None. G.F. Fagundes: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. M.A. Pereira: None. A. Pio-Abreu: None. L.A. Bortolotto: None. A. Latronico: None. M.B. Fragoso: None. L.F. Drager: None. B.B. Mendonca: None. M.Q. Almeida: None. Background: Primary aldosteronism (PA) is a very prevalent disease, characterized by an autonomous aldosterone secretion. Unilateral PA accounts for approximately 40% of the cases and is preferentially treated with surgery. Several studies reported decrease in renal function following unilateral adrenalectomy, but the risk factors associated with this decline remain to be better elucidated. Aim: Our aim was to investigate predictive factors of the decrease in renal function after unilateral adrenalectomy for PA. Methods: We retrospectively evaluated 89 PA patients submitted to unilateral adrenalectomy. Serum aldosterone, direct renin concentration, estimated glomerular filtration rate (eGFR), and electrolytes were determined at the pre-operative period and at 1 week, 1, 3 and 6 months (m) after unilateral adrenalectomy. The primary endpoint was the DELTAeGFR (eGFR after surgery at different times – eGFR before surgery). Results: Thirty-seven patients (41.6%) were men and 52 (58.4%) were women, with a median age of diagnosis of 49 years (range, 20 to 74 years). At diagnosis, the median aldosterone and renin levels were 29.8 ng/dl (7.3 - 217) and 4 μIU/mL (4 – 8.2), respectively. Hypokalemia at diagnosis was evidenced in 75 out of 89 (84.3%) of the patients. Unilateral PA was confirmed in 78 out of 89 cases (87.6%) by biochemical cure after adrenalectomy. The mean pre-operative creatinine and eGFR were 1.14 ± 0.48 mg/dL and 53.5 ± 17.1 mL/min, respectively. After adrenalectomy, the DELTAeGFR was −6.7 ± 12.1 mL/min at 1 week (p= 0.001), 0.17 ± 10 mL/min at 1m (p= 0.91), −2 ± 8.7 mL/min at 3m (p= 0.13) and −1.8 ± 10.9 mL/min at 6m (p= 0.24). Interestingly, aldosterone levels at diagnosis were significantly associated with the DELTAeGFR at 1 week (p= 0.024). PA patients with aldosterone levels & gt;50 ng/dL (n= 13) at diagnosis presented a higher deterioration in renal function at 1 week when compared to those with aldosterone & lt;50 ng/dL (n= 76) (αeGFR −12 ± 8.6 mL/min vs. −5.9 ± 12.5 mL/min, respectively; p= 0.032). Moreover, the patients with hypoaldosteronism (aldosterone & lt;5 ng/dl) at 1 week had a lower decrease in renal function (DELTAeGFR −4.4 ± 12mL/min (n= 41) vs. −9.9 ± 11.6 mL/min (n= 42), respectively; p= 0.014) and lower levels of aldosterone at diagnosis (31.5 ± 21.1 ng/dL vs. 50.4 ± 44.4 ng/dL, respectively; p= 0.008). The post-operative decline in renal function did not correlate with age, hypokalemia, number of anti-hypertensive medications at diagnosis, immediate pre-operative and post-operative renin, and hypertension remission after surgery. Conclusion: The renal function decreased precociously after adrenalectomy but returned to basal levels after 1m. Aldosterone levels at diagnosis and at 1 week after surgery were significantly associated with decline in renal function. Support: This work was supported by the Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 2
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 5 ( 2023-04-13), p. 1143-1153
    Abstract: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level & lt;15 ng/dL, 19.9% had at least 2 aldosterone levels & lt;15 ng/dL, and 16.2% had mean aldosterone levels & lt;15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC & gt;2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 3
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None. Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p & lt; 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p & lt; 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p & lt; 0.001 and p & lt; 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity. Presentation: Thursday, June 15, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 4
    In: Heart, BMJ, Vol. 108, No. 24 ( 2022-12), p. 1952-1956
    Abstract: To test the impact of directly observed therapy (DOT) at hospital for checking not only adherence/diagnosis in patients with resistant (RHTN) and refractory (RefHTN) hypertension but also blood pressure (BP) control after hospital discharge. Methods During 2 years, Brazilian patients with clinical suspicion of RHTN/RefHTN after several attempts (≥3) to control BP in the outpatient setting were invited to perform DOT (including low-sodium diet and supervised medications intake) at the hospital. RHTN and RefHTN were categorised using standard definitions. After hospital discharge, we evaluated the BP values and the number of antihypertensive drugs prescribed by physicians who were not involved with the investigation. Results We studied 83 patients clinically suspected for RHTN (31%) and RefHTN (69%) (mean age: 53 years; 76% female; systolic BP 177±28 mm Hg and diastolic BP 106±21 mm Hg; number of antihypertensive drugs: 5.3±1.3). DOT confirmed RHTN in 77%, whereas RefHTN was confirmed in only 32.5%. The number of antihypertensive drugs reduced to 4.5±1.3 and systolic/diastolic BP at hospital discharge reduced to 131±17 mm Hg/80±12 mm Hg. After hospital discharge, systolic BP remained significantly lower than the last outpatient visit prehospital admission (delta changes (95% CI): 1 month: −25.7 (−33.8 to −17.6) mm Hg; 7 months: −27.3 (−35.5 to −19.1) mm Hg) despite fewer number of antihypertensive classes (1 month: −1.01 (−1.36 to −0.67); 7 months: −0.77 (−1.11 to −0.42)). Similar reductions were observed for diastolic BP. Conclusions DOT at hospital is helpful not only in confirming/excluding RHTN/RefHTN phenotypes, but also in improving BP values and BP control and in reducing the need for antihypertensive drugs after hospital discharge.
    Type of Medium: Online Resource
    ISSN: 1355-6037 , 1468-201X
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2378689-9
    detail.hit.zdb_id: 1475501-4
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  • 5
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 10 ( 2019-10-01), p. 4695-4702
    Abstract: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure 〈 140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. Objective To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA. Methods We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. Results KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration 〈 10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004). Conclusion The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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