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1.
Urology ; 135: e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31604068

RESUMO

A 29-year-old female was referred to the urology clinic because of an incidentally found left renal mass discovered during workup for secondary erythrocytosis. Since 12 years of age, she has had headaches and poorly controlled hypertension refractory to trimodal antihypertensive therapy. Laboratory workup revealed markedly elevated aldosterone and renin levels. Computed tomography demonstrated a 3 cm left renal mass. The patient was admitted for intravenous blood pressure control. After partial nephrectomy, aldosterone and renin levels normalized. The patient was weaned off of blood pressure medications. Pathology was consistent with a juxtaglomerular cell tumor secreting renin (ie, reninoma).


Assuntos
Anti-Hipertensivos/farmacologia , Hipertensão/etiologia , Sistema Justaglomerular/patologia , Neoplasias Renais/complicações , Adulto , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Sistema Justaglomerular/diagnóstico por imagem , Sistema Justaglomerular/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia , Renina/sangue , Renina/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
J Chromatogr A ; 1609: 460456, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31471132

RESUMO

Accurate quantitation of aldosterone is critical for the clinical detection of hypertension. However, no reference intervals for aldosterone in healthy volunteers and patients with hypertension have yet been established using highly sensitive methods with a wide linear range based on low plasma volumes. We developed a modified ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantitation of aldosterone and established reference intervals for healthy volunteers and patients with hypertension. We measured aldosterone by UPLC-MS/MS in human plasma samples (90 µL). We established a reference range for aldosterone based on blood collected midmorning from 888 patients with hypertension and 258 seated, normotensive subjects. The linear range was 10-5000 pg/mL (r2 > 0.995), with a limit of quantification of 10 pg/mL. Similar results were obtained using different collection tubes, including EDTA plasma, sodium citrate plasma, and serum, respectively. Based on a comparison of results from UPLC-MS/MS and enzyme-linked immunosorbent assay, we derived the equation: UPLC-MS/MS = 0.8444 × ELISA + 1.162. Aldosterone concentrations in normotensive subjects ranged from 12.76 to 196.21 pg/mL, with no effect of age or sex on the reference interval. Aldosterone levels were significantly higher in patients with hypertension versus healthy controls (median: 71.05 versus 52.54 pg/mL, P < 0.0001), and patients with secondary hypertension versus primary hypertension (median: 67.25 versus 46.70 pg/mL, P = 0.0128) which were age- and sex-matched. Reference intervals for aldosterone in healthy individuals and patients with hypertension were established based on an improved UPLC-MS/MS method with higher sensitivity, a wider linear range, and lower plasma volume.


Assuntos
Aldosterona/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Feminino , Voluntários Saudáveis , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes , Adulto Jovem
3.
Clin Exp Hypertens ; 42(1): 93-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31204516

RESUMO

Introduction: There is no study evaluating the Tp-e/QT and Tp-e/QTc ratios with T wave peak to end interval (Tp-e interval) used for evaluation of cardiac arrhythmia risk and ventricular repolarization changes in patients with primary aldosteronism (PA). We aimed to investigate whether there was a change in Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in patients with PA.Method: Thirty patients with newly diagnosed hypertension (HT) and PA and 30 patients with primary HT were included. Twelve-lead electrocardiography (ECG) was performed in all patients. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured in addition to routine measurements in ECG.Results: Sodium, potassium, and plasma renin activity (PRA) were significantly lower in patients with PA; systolic and diastolic blood pressure, plasma aldosterone, plasma aldosterone/PRA were significantly higher in patients with PA (p < .05 for each one). When ventricular repolarization parameters were examined; while QT and QTc interval were similar between two groups, Tp-e interval, Tp-e/QT and Tp-e/QTc ratio values were significantly higher in patients with PA (p < .05 for each one). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio values were positively correlated with the serum calcium, aldosterone, and aldosterone/PRA levels and negatively correlated with serum sodium, potassium, renin levels (p < .05 for each one). In linear regression analyses, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were independently associated with the aldosterone/PRA ratio.Conclusion: Tp-e interval, Tp-e/QT and Tp-e/QTc were increased in hypertensive patients with PA and were independently associated with aldosterone/PRA levels. This may be related to the changing neuroendocrine state in patients with PA.


Assuntos
Aldosterona/sangue , Ventrículos do Coração/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Hipertensão/fisiopatologia , Renina/sangue , Adulto , Pressão Sanguínea , Cálcio/sangue , Doença do Sistema de Condução Cardíaco , Eletrocardiografia , Feminino , Humanos , Hiperaldosteronismo/complicações , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Sódio/sangue
5.
Presse Med ; 48(12): 1445-1455, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31761607

RESUMO

The Hormonal assessment of Arterial Hypertension (HTA) is an important part of the balance of resistant hypertension. This assessment - going well beyond the search for primary hyperaldosteronism (PHA) - requires a rigorous methodology and a robust experience of the nursing team within a dedicated unit: the HTA Day Hospital. If all the conditions are met and the assessment carried out well, it will allow a significant profitability since in this resistant hypertensive population it will detect a particular mechanism or secondary hypertension in 70% of patients. Since the diagnosis of PHA is essentially biological, the proper execution of the various stages of the assessment is essential to its documentation.


Assuntos
Técnicas de Diagnóstico Endócrino , Hormônios/análise , Hipertensão/diagnóstico , Aldosterona/análise , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Resistência a Medicamentos/efeitos dos fármacos , Hormônios/sangue , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Renina/análise , Renina/sangue
6.
Presse Med ; 48(11 Pt 1): 1265-1268, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732366

RESUMO

The two main non-iatrogenic causes of secondary hypertension in women of childbearing age are primary aldosteronism and renal fibromuscular dysplasia. It is recommended to look for a secondary hypertension in women who remain hypertensive three months after pregnancy, in patients under 40 years of age or in patients with a grade 3 HTN (BP≥180/110mm Hg) (Professional agreement). It is suggested that the initial assessment of a secondary HTN in women is performed by a HTN specialist; it will include an assessment of renin and aldosterone concentrations and an angio-CT of the renal arteries (or angio-MRI if contraindicated) (Grade C - Class 2).


Assuntos
Displasia Fibromuscular/complicações , Hiperaldosteronismo/complicações , Hipertensão/etiologia , Adulto , Fatores Etários , Aldosterona/sangue , Angiografia por Tomografia Computadorizada , Feminino , Displasia Fibromuscular/diagnóstico , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/diagnóstico , Período Pós-Parto , Artéria Renal/diagnóstico por imagem , Renina/sangue , Fatores Sexuais
7.
BMC Infect Dis ; 19(1): 866, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638922

RESUMO

BACKGROUND: Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). METHODS: A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. RESULTS: Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] µg/L/h, P = 0.029), CONCLUSIONS: CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.


Assuntos
Doenças Cardiovasculares/terapia , Enterovirus Humano A , Doença de Mão, Pé e Boca/terapia , Doença de Mão, Pé e Boca/virologia , Unidades de Terapia Intensiva Pediátrica , Doença Pulmonar Obstrutiva Crônica/terapia , Aldosterona/sangue , Angiotensina II/sangue , Doenças Cardiovasculares/complicações , Catecolaminas/sangue , Pré-Escolar , China , Feminino , Seguimentos , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/complicações , Hemodiafiltração/métodos , Humanos , Lactente , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Renina/sangue , Sistema Renina-Angiotensina/fisiologia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento
8.
Endocr Regul ; 53(3): 154-164, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517630

RESUMO

OBJECTIVES: Aldosterone rapidly enhances protein kinase C (PKC) alpha and beta1 proteins in the rat kidney. The G protein-coupled receptor 30 (GPR30)-mediated PKC pathway is involved in the inhibition of the potassium channel in HEK-239 cells. GPR30 mediates rapid actions of aldosterone in vitro. There are no reports available regarding the aldosterone action on other PKC isoforms and GPR30 proteins in vivo. The aim of the present study was to examine rapid actions of aldosterone on protein levels of phosphorylated PKC (p-PKC) delta, p-PKC epsilon, and GPR30 simultaneously in the rat kidney. METHODS: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150 µg/kg body weight). After 30 minutes, abundance and immunoreactivity of p-PKC delta, p-PKC epsilon, and GPR30 were determined by Western blot analysis and immunohisto-chemistry, respectively. RESULTS: Aldosterone administration significantly increased the renal protein abundance of p-PKC delta by 80% (p<0.01) and decreased p-PKC epsilon protein by 50% (p<0.05). Aldosterone injection enhanced protein immunoreactivity of p-PKC delta but suppressed p-PKC epsilon protein intensity in both kidney cortex and medulla. Protein abundance of GPR30 was elevated by aldosterone treatment (p<0.05), whereas the immunoreactivity was obviously changed in the kidney cortex and inner medulla. Aldosterone translocated p-PKC delta and GPR30 proteins to the brush border membrane of proximal convoluted tubules. CONCLUSIONS: This is the first in vivo study simultaneously demonstrating that aldosterone administration rapidly elevates protein abundance of p-PKC delta and GPR30, while p-PKC epsilon protein is suppressed in rat kidney. The stimulation of p-PKC delta protein levels by aldosterone may be involved in the activation of GPR30.


Assuntos
Aldosterona/farmacologia , Rim/efeitos dos fármacos , Proteína Quinase C-delta/metabolismo , Proteína Quinase C-épsilon/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Aldosterona/sangue , Aldosterona/urina , Animais , Rim/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Proteína Quinase C-delta/efeitos dos fármacos , Proteína Quinase C-épsilon/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Fatores de Tempo
9.
Hypertension ; 74(4): 800-808, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476901

RESUMO

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Adrenalectomia , Aldosterona/sangue , Hiperaldosteronismo/sangue , Adulto , Coleta de Amostras Sanguíneas , Feminino , Humanos , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
Hypertension ; 74(4): 793-799, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476908

RESUMO

AT1AA (Angiotensin II type-1 receptor autoantibodies) were first detected in patients with primary aldosteronism (PA) because of aldosterone-producing adenoma (APA) with an in-house developed assay, but it remained unclear if they can be ascertained also with commercially available assays and if they have a functional role. Aims of our study were to investigate if (1) commercially available kits allow detection of raised AT1AA titer in APA; (2) this titer is normalized by adrenalectomy; and (3) AT1AA display any biological roles in vitro. We measured with 2 ELISA kits the AT1AA titer in serum of APA patients and its changes after adrenalectomy. We also investigated AT1AA bioactivity by using AT1-R (angiotensin type-1 receptor)-transfected Chinese hamster ovary and human adrenocortical carcinoma cells, and by measuring aldosterone synthase (CYP11B2) expression in human adrenocortical carcinoma cells after incubation with IgG. Both kits allowed detection of higher AT1AA levels in APA patients than in healthy subjects; surgical cure of PA did not decrease this titer at 1-month follow-up. Human adrenocortical carcinoma cells stimulation with IgG purified from sera of APA patients increased both CYP11B2 expression and aldosterone release (+40% and +76%, respectively, versus healthy subjects). However, no detectable effect of IgG was seen in Chinese hamster ovary cells expressing AT1-R. These findings support the contentions that (1) the raised AT1AA titer does not seem to be a consequence of hyperaldosteronism as it did not normalize after its cure; (2) AT1AA act as weak stimulators of aldosterone biosynthesis, but this effect can be identified only by using a sensitive in vitro technique.


Assuntos
Aldosterona/sangue , Autoanticorpos/sangue , Hiperaldosteronismo/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Adrenalectomia , Adulto , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade
11.
J Toxicol Sci ; 44(9): 575-584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474739

RESUMO

The adrenal gland is the most common toxicological target of drugs within the endocrine system, and inhibition of adrenal steroidogenesis can be fatal in humans. However, methods to evaluate the adrenal toxicity are limited. The aim of the present study was to verify the usefulness of simultaneous measurement of blood levels of multiple adrenal steroids, including precursors, as a method to evaluate drug effects on adrenal steroidogenesis in cynomolgus monkeys. With this aim, physiological and drug-induced changes in blood levels of adrenal steroids, including cortisol, aldosterone, androgen, and their precursors were examined. First, for physiological changes, intraday and interday changes in blood steroid levels were examined in male and female cynomolgus monkeys. The animals showed circadian changes in steroid levels that are similar to those in humans, while interday changes were relatively small in males. Next, using males, changes in blood steroid levels induced by ketoconazole and metyrapone were examined, which suppress adrenal steroidogenesis via inhibition of CYP enzymes. Consistent with rats and humans, both ketoconazole and metyrapone increased the deoxycorticosterone and deoxycortisol levels, probably via CYP11B1 inhibition, and the increase was observed earlier and with greater dynamic range than the changes in cortisol level. Changes in other steroid levels reflecting the drug mechanisms were also observed. In conclusion, this study showed that in cynomolgus monkeys, simultaneous measurement of blood levels of adrenal steroids, including precursors, can be a valuable method to sensitively evaluate drug effects on adrenal steroidogenesis and to investigate the underlying mechanisms.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Aldosterona/sangue , Aldosterona/metabolismo , Androgênios/sangue , Androgênios/metabolismo , Cromatografia Líquida/métodos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Cetoconazol/toxicidade , Metirapona/toxicidade , Espectrometria de Massas em Tandem/métodos , Animais , Ritmo Circadiano , Desoxicorticosterona/metabolismo , Feminino , Humanos , Macaca fascicularis , Masculino , Esteroide 11-beta-Hidroxilase/antagonistas & inibidores
12.
Hypertension ; 74(4): 903-909, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378103

RESUMO

True drug-resistant hypertension (RHT) is characterized by a marked neuroadrenergic activation and reflex alterations compared with the nonresistant hypertensive state. It is unknown however, whether this behavior is specific for the RHT state or is also shared by apparent RHT (ARHT). In 38 middle-age patients with RHT, 44 treated essential controlled hypertensives (HT) and 32 ARHT; we evaluated sphygmomanometric, beat-to-beat (Finapres) and 24-hour (Spacelabs) blood pressure, heart rate and muscle sympathetic nerve traffic (microneurography). Measurements included plasma aldosterone, plasma norepinephrine, homeostasis model assessment index, and spontaneous baroreflex-muscle sympathetic nerve traffic sensitivity. All the various above-mentioned blood pressure values were significantly greater in both RHT and ARHT as compared with HT, while 24-hour blood pressure was significantly lower in ARHT as compared with RHT. In ARHT, muscle sympathetic nerve traffic was significantly lower than RHT (74.8±5.2 versus 89.2±4.8 bursts/100 hb, P<0.01) and similar to HT (69.7±4.8 bursts/100 hb, P=NS). RHT showed, at variance from the other 2 groups, greater plasma aldosterone and homeostasis model assessment index values and an impaired baroreflex function. In RHT, but not in ARHT and HT, muscle sympathetic nerve traffic was significantly and inversely related to baroreflex function (r=-0.40, P<0.02) and directly to plasma aldosterone and homeostasis model assessment index values (r=0.34-0.36, P<0.05). Plasma norepinephrine and heart rate values were not significantly different in the 3 groups. These data provide evidence that the marked sympathetic activation and baroreflex dysfunction detected in RHT is not present in ARHT, which displays a sympathetic and baroreflex profile superimposable to that seen in HT. These differences in the neurogenic function may have important clinical and therapeutic implications.


Assuntos
Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Aldosterona/sangue , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/sangue , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue
13.
J Renin Angiotensin Aldosterone Syst ; 20(3): 1470320319870891, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434530

RESUMO

INTRODUCTION: The captopril challenge test (CCT) is the major confirmatory test for primary aldosteronism (PA), and frequently carried out because of its convenience. However, it presents false-negative results with a certain probability, and as there are many criteria for CCT, it is not concluded yet which criteria to use. MATERIALS AND METHODS: A total of 71 PA patients were evaluated. We compared CCT-positive and CCT-negative patients in the following three criteria: plasma aldosterone/renin ratio (ARR) >200 after the CCT (criterion 1); plasma aldosterone concentration (PAC) >120 pg/ml after the CCT (criterion 2); and PAC suppression <30% of PAC before CCT (criterion 3). RESULTS: The positive rate was 70.4%, 64.8% and 54.9% for criterion 1, criterion 2 and criterion 3, respectively. With criterion 1, the baseline plasma renin activity was lower, thus baseline ARR was higher in CCT-positive patients. With criterion 2, PAC was higher and estimated sodium intake and K were lower in CCT-positive patients. With criterion 3, K and PAC were lower in CCT-positive patients. Although it was not significant, in the patients with high sodium intake, the positive rate of criterion 1 was higher than that of the other criteria. CONCLUSIONS: ARR>200 is the valuable criterion for the diagnosis of PA.


Assuntos
Captopril/uso terapêutico , Aldosterona/sangue , Captopril/farmacologia , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Renina/sangue
14.
Ther Adv Cardiovasc Dis ; 13: 1753944719868134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31401939

RESUMO

Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (AT1R) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or 'sartans', short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT1 receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of AT1R, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the adrenal cortex, thirst-fluid intake (hypervolemia), etc., the ARBs are nowadays one of the most useful cardiovascular drug classes used in clinical practice. However, significant differences in their pharmacological and clinical properties exist that may favor use of particular agents over others within the class, and, in fact, two of these drugs, candesartan and valsartan, continuously appear to distinguish themselves from the rest of the 'pack' in recent clinical trials. The reason(s) for the potential superiority of these two agents within the ARB class are currently unclear but under intense investigation. The present short review gives an overview of the clinical properties of the ARBs currently approved by the United States Food and Drug Administration, with a particular focus on candesartan and valsartan and the areas where these two drugs seem to have a therapeutic edge. In the second part of our review, we outline recent data from our laboratory (mainly) on the molecular effects of the ARB drugs on aldosterone production and on circulating aldosterone levels, which may underlie (at least in part) the apparent clinical superiority of candesartan (and valsartan) over most other ARBs currently in clinical use.


Assuntos
Aldosterona/sangue , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Benzimidazóis/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Animais , Biomarcadores/sangue , Regulação para Baixo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento
16.
Int J Hyperthermia ; 36(1): 905-914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466482

RESUMO

Objective: To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. Method: An in-vivo study was carried out in swine (n = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia. Results: Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (∼0.8 cm3) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically. Conclusion: MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.


Assuntos
Técnicas de Ablação , Hiperaldosteronismo/terapia , Hipertermia Induzida , Micro-Ondas/uso terapêutico , Córtex Suprarrenal/cirurgia , Hormônio Adrenocorticotrópico/sangue , Aldosterona/sangue , Animais , Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Masculino , Metanefrina/sangue , Normetanefrina/sangue , Suínos
17.
Eur J Endocrinol ; 181(4): R147-R153, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299637

RESUMO

In patients with primary aldosteronism, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension. Prognostic relevance has been shown for adrenalectomy in unilateral disease and for medical treatment with mineralocorticoid receptor antagonists in bilateral adrenal hyperplasia. Collectively, evidence points to the superiority of surgical treatment compared to medical treatment. The causal approach of removing the mineralocorticoid excess, as well as the often-accompanying glucocorticoid excess, might provide one biologically plausible explanation for the observation of slightly better outcomes with surgical therapy. However, in patients living with primary aldosteronism, medical treatment is often insufficient for three major reasons. First and foremost, no marker of sufficient aldosterone blockade has yet been established and therefore adequate treatment of the aldosterone excess is often dismissed as a treatment goal. Second, side effects often limit patient compliance. Third, as recommendations differ from other indications like heart failure, drug dosing is often inadequate. The aim of this review is first to provide an overview over medical treatment options and second to review potential markers for treatment surveillance in patients with primary aldosteronism.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/terapia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Adrenalectomia/métodos , Humanos , Resultado do Tratamento
18.
Medicina (B Aires) ; 79(3): 185-190, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284252

RESUMO

The diagnosis of primary hyperaldosteronism (PHPA) has progressively increased over the last years and some authors consider it as the main cause of secondary hypertension. We studied the prevalence of PHPA in hypertensive patients followed at the Hypertension Unit from July 1999 to July 2017. A total of 2500 patients were included and diagnosis of PHPA was done in 79 of them (3.2%). It was more frequent in women (55.7%) with an increased incidence in the elderly, as compared to previous studies (27.8%). Initial diagnosis was suspected upon the presence of inappropriate kaliuria and metabolic alkalosis, associated to an aldosterone/plasma renin activity ratio > 30 (ng/dl)/(ng/ml/h). After confirmation of the presence of PA, imaging techniques to determine the etiology were performed. In this way, 29 cases (36.8%) of aldosterone-producing adenoma and 5 cases of bilateral adrenal hyperplasia with nodules were identified. Computed tomography identified the adenomas and hyperplasias with bilateral cortical nodules in all patients. Adrenalectomy and/or antialdosteronics were efficient in controlling blood pressure in 69.9% of cases. Of note in this series was the remission of stage 3 chronic renal failure in two cases, the high prevalence of hypercalciuric urinary lithiasis and a case of breast carcinoma after prolonged treatment with spironolactone.


Assuntos
Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Idoso , Aldosterona/sangue , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Masculino , Pessoa de Meia-Idade , Renina/sangue , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Intern Med ; 58(21): 3107-3111, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292373

RESUMO

During the malignant phase of hypertension in patients with primary aldosteronism complicated with severe renal failure, the plasma renin activity may markedly increase with a false negative screening result for primary aldosteronism, thus potentially leading to a missed diagnosis of primary aldosteronism. We herein report the case of 37-year-old man who presented with accelerated-malignant hypertension complicated with severe renal insufficiency. The plasma renin activity was markedly increased in the malignant phase of hypertension, which were atypical results for primary aldosteronism. However, a plain abdominal computed tomography scan revealed a left adrenal nodule, which was diagnosed as aldosterone-producing adenoma by adrenal venous sampling.


Assuntos
Adenoma/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico , Hipertensão Maligna/etiologia , Insuficiência Renal/complicações , Renina/sangue , Adenoma/complicações , Adenoma/patologia , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Aldosterona/sangue , Humanos , Hiperaldosteronismo/complicações , Masculino , Tomografia Computadorizada por Raios X
20.
Eur J Endocrinol ; 181(3): 339-350, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319380

RESUMO

Objective: Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. Design: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). Methods: We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. Results: Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. Conclusion: Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/epidemiologia , Nefropatias/sangue , Nefropatias/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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