RESUMEN
AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5âyears and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% ( n â=â84), with 75% of cases classified as state 3a ( n â=â63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases ( n â=â330), and 459 patients were treated with MRA. After a median follow-up of 30.7âmonths (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, P â=â0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.
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Adrenalectomía , Hiperaldosteronismo , Antagonistas de Receptores de Mineralocorticoides , Sistema de Registros , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , España/epidemiología , Estudios Retrospectivos , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Anciano , Riñón/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Adulto , Tasa de Filtración Glomerular , Estudios de CohortesRESUMEN
This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non-dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24-h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24-h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone-renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24-h wSD of systolic BP (ß = 0.383).The study also found significant correlations between the 24-h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24-h urinary microalbumin, underscoring the critical role of the 24-h wSD of systolic BP (ß = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.
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Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Tasa de Filtración Glomerular , Hiperaldosteronismo , Hipertensión , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Tasa de Filtración Glomerular/fisiología , Hipertensión/fisiopatología , Hipertensión/epidemiología , Adulto , Albuminuria/fisiopatología , Ritmo Circadiano/fisiología , Creatinina/sangre , Cistatina C/sangre , Hipertensión Esencial/fisiopatología , Hipertensión Esencial/complicaciones , Renina/sangre , Aldosterona/sangreAsunto(s)
Adenoma , Adenoma Corticosuprarrenal , Hiperaldosteronismo , Humanos , Aldosterona , Adrenalectomía , Adenoma Corticosuprarrenal/genética , Mutación , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/genética , Hiperaldosteronismo/fisiopatología , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/genéticaRESUMEN
Primary aldosteronism (PA) is the primary cause of secondary hypertension. The prevalence of PA has probably been underestimated in the past and recent studies suggest that PA could be present in up to 10% of patients suffering from hypertension. Aldosterone excess in PA can be caused by unilateral adrenal disease, usually adrenal adenoma, or bilateral adrenal hyperplasia. Differentiation between unilateral and bilateral disease is clinically important as the former can effectively be treated by removal of the affected adrenal. CT or MRI cannot reliably distinguish unilateral from bilateral disease. Therefore, adrenal vein sampling (AVS) is an important step of the diagnostic work-up in patients with PA. Current guidelines recommend PA in virtually all patients with biochemically diagnosed PA who would undergo adrenal surgery if unilateral PA was diagnosed. In this narrative review, we give an overview of the current technique used for AVS with a focus on the experience with this technique at the University Hospital Basel, Switzerland.
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Glándulas Suprarrenales/irrigación sanguínea , Aldosterona/sangre , Hiperaldosteronismo/diagnóstico , Glándulas Suprarrenales/diagnóstico por imagen , Recolección de Muestras de Sangre , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico por imagen , Hiperaldosteronismo/fisiopatología , Hipertensión/etiología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , VenasRESUMEN
BACKGROUND: Adrenalectomy cures unilateral primary aldosteronism, and it improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success postsurgery, suggesting that surgery was ineffective. METHODS: We assessed all patients 6 to 12 months post-surgery for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2, and CONNsortium criteria. We estimated blood pressure changes after adjustment for changes in defined daily dosages of antihypertensive medications. We also reassessed all patients using PASO at their recent clinical visit. RESULTS: A total of 104 patients with unilateral primary aldosteronism underwent adrenalectomy at 2 tertiary centers from 2000 to 2019; 24 (23%), 31 (30%), and 54 (52%) patients were classified with absent clinical success using PASO, AVIS-2, and CONNsortium criteria, respectively. Among 24 patients with absent clinical success using PASO criteria, 10 had complete biochemical cure, 3 partial, 2 absent, and 9 had resolution of hypokalemia. On multivariable analysis, absent clinical success was associated with presence of hyperlipidemia, diabetes mellitus, and lower defined daily dosages at baseline. After adjustment for changes in defined daily dosages, 7 of 24 patients showed blood pressure improvement ≥20/10 mm Hg post-surgery. After a follow-up of mean 5.6 years, 12 of 24 patients showed partial or complete clinical success when reassessed using PASO criteria. Only 6 of 104 (5.8%) patients failed to show clinical improvement post-surgery using any of the 3 mentioned criteria or using PASO criteria at their recent clinical visit. CONCLUSION: Although some patients may be classified with absent clinical success post-surgery, the assessment of clinical outcomes remains subject to many variables. In patients with unilateral primary aldosteronism, evidenced by lateralization on AVS, unilateral adrenalectomy should remain the recommended treatment.
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Adrenalectomía/métodos , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Hiperaldosteronismo/cirugía , Hipertensión/terapia , Evaluación de Resultado en la Atención de Salud , Cuidados Posoperatorios/métodos , Femenino , Estudios de Seguimiento , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Hipertensión/etiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Normotensive patients with primary aldosteronism (PA) are relatively rare. Herein, we report two patients with normotensive PA and present a literature review to improve an understanding of the disease. Patient 1, a 56-year-old man, presented with recurrent hypokalemia that lasted for more than 2 years. Patient 2 was a 33-year-old man who presented with sexual dysfunction and was diagnosed with a prolactinoma combined with adrenal insufficiency and hypogonadism. Neither of these patients had hypertension that was detectable on repeated manual measurements. In both patients, a typical biological profile of PA was demonstrated that included hypokalemia with kaliuresis, elevated plasma aldosterone concentration (PAC), suppressed plasma renin concentration, and a high aldosterone-to-renin ratio. Both patients did not have sufficiently suppressed PAC on the saline infusion test, confirming the diagnosis of PA. Computed tomography of the adrenal gland and adrenal venous sampling suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected. As hypertension is not necessarily a sign of PA, we propose that all patients with hypokalemia should be screened for PA in order to prevent cardiovascular complications while balancing economics and effectiveness.
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Presión Sanguínea/fisiología , Hiperaldosteronismo/fisiopatología , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Glándulas Suprarrenales/fisiopatología , Adulto , Medios de Contraste , Humanos , Hiperaldosteronismo/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To investigate whether adrenal volumetry provides better agreement with adrenal vein sampling (AVS) than conventional CT for subtyping PA. Furthermore, we evaluated whether the size of this contralateral adrenal was a prognostic factor for clinical outcome after unilateral adrenalectomy. METHODS: We retrospectively analyzed volumes of both adrenal glands of the 180 CT-scans (88/180 with unilateral and 92/180 with bilateral disease) of the patients with PA included in the SPARTACUS trial of which 85 also had undergone an AVS. In addition, we examined CT-scans of 20 healthy individuals to compare adrenal volumes with published normal values. RESULTS: Adrenal volume was higher for the left than the right adrenal (mean and SD: 6.49 ± 2.77 ml versus 5.25 ± 1.87 ml for the right adrenal; p < 0.001). Concordance between volumetry and AVS in subtyping was 58.8%, versus 51.8% between conventional CT results and AVS (p = NS). The volumes of the contralateral adrenals in the patients with unilateral disease (right 4.78 ± 1.37 ml; left 6.00 ± 2.73 ml) were higher than those of healthy controls reported in the literature (right 3.62 ± 1.23 ml p < 0.001; left 4.84 ± 1.67 ml p = 0.02). In a multivariable analysis the contralateral volume was not associated with biochemical or clinical success, nor with the defined daily doses of antihypertensive agents at 1 year follow-up. CONCLUSIONS: Volumetry of the adrenal glands is not superior to current assessment of adrenal size by CT for subtyping patients with PA. Furthermore, in patients with unilateral disease the size of the contralateral adrenal is enlarged but its size is not associated with outcome.
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Glándulas Suprarrenales , Aldosterona/sangre , Tomografía Computarizada de Haz Cónico , Hiperaldosteronismo , Tomografía Computarizada por Rayos X , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/patología , Antihipertensivos/uso terapéutico , Tomografía Computarizada de Haz Cónico/métodos , Tomografía Computarizada de Haz Cónico/estadística & datos numéricos , Correlación de Datos , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/clasificación , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatología , Hipertensión/etiología , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Tamaño de los Órganos , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/estadística & datos numéricosRESUMEN
INTRODUCTION: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. METHODS: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). RESULTS: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. CONCLUSIONS: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.
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Biomarcadores/metabolismo , Endotelio Vascular/fisiopatología , Hipertensión Esencial/complicaciones , Hipertensión Esencial/fisiopatología , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Microvasos/fisiopatología , Arginina/análogos & derivados , Arginina/sangre , Homólogo de la Proteína Chromobox 5 , Selectina E/sangre , Hipertensión Esencial/sangre , Femenino , Humanos , Hiperaldosteronismo/sangre , Masculino , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/sangre , Rigidez VascularRESUMEN
Conn's syndrome is an important endocrine cause for secondary hypertension. Hypokalaemia paralysis and rhabdomyolysis with accelerated hypertension may be the presenting symptoms of Conn's syndrome. Here, we present one such case of a 38-year-old woman presenting with accelerated hypertension and acute onset quadriplegia. On biochemical evaluation, she was found to have severe hypokalaemia, metabolic alkalosis and elevated creatinine phosphokinase. Further evaluation revealed an elevated aldosterone renin ratio suggestive of primary hyperaldosteronism which was localised to left adrenal adenoma on contrast-enhanced CT. Patient's blood pressure and serum potassium levels normalised after resection of the adrenal adenoma.
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Neoplasias de la Corteza Suprarrenal/complicaciones , Adenoma Corticosuprarrenal/complicaciones , Hiperaldosteronismo/etiología , Hipopotasemia/etiología , Cuadriplejía/etiología , Rabdomiólisis/etiología , Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Neoplasias de la Corteza Suprarrenal/cirugía , Adenoma Corticosuprarrenal/diagnóstico por imagen , Adenoma Corticosuprarrenal/cirugía , Adulto , Alcalosis/etiología , Creatina Quinasa , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/cirugía , Hipertensión/etiología , Tomografía Computarizada por Rayos XRESUMEN
Patients with primary aldosteronism (PA) are at increased cardiovascular risk, compared to patients with essential hypertension (EH). Cardiovascular damage could depend on PA phenotype, potentially being lower in milder forms of PA. Our aim was to assess atherosclerotic burden and arterial stiffness in 88 prospectively recruited patients, including 44 patients with mild PA and EH respectively. All patients underwent a structured study program, including measurements of ankle-brachial index, oscillometric measurement of central pulse wave velocity (cPWV) and vascular ultrasound examination of the supraaortic arteries, the abdominal aorta, and the femoropopliteal arteries. A plaque score was calculated to estimate atherosclerotic burden for each patient. This is a prospective case-control study set at a tertiary care hospital. Patients with PA and EH matched well for age, gender, blood pressure, BMI, and cardiovascular risk factors such as diabetes mellitus and smoking status. Common carotid intima-media thickness (0.77 vs. 0.75 mm; p=0.997) and cPWV (7.2 vs. 7.1 m/s; p=0.372) were comparable between patients with PA and EH. The atherosclerotic burden, as expressed by the plaque score, did not differ between the two groups (p=0.159). However, after initiation of treatment cPWV was significantly decreased in patients with PA (p=0.017). This study shows that subclinical atherosclerotic burden and arterial stiffness in patients with milder forms of PA is comparable to patients with EH. Nevertheless, specific treatment for PA significantly improved cPWV, which argues for a more liberal use of mineralocorticoid receptor antagonists in patients with arterial hypertension.
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Hipertensión Esencial/fisiopatología , Hiperaldosteronismo/fisiopatología , Rigidez Vascular , Anciano , Índice Tobillo Braquial , Aterosclerosis/diagnóstico , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/etiología , Presión Sanguínea , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Hipertensión Esencial/complicaciones , Hipertensión Esencial/diagnóstico por imagen , Femenino , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de la Onda del Pulso , Arteria Vertebral/diagnóstico por imagenRESUMEN
Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016. Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis. Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.
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Hiperaldosteronismo/fisiopatología , Hipertensión/fisiopatología , Hipopotasemia/sangre , Obstrucción de la Arteria Renal/fisiopatología , Adulto , Aldosterona/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Errores Diagnósticos , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Hipopotasemia/etiología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Obstrucción de la Arteria Renal/sangre , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/diagnóstico , Renina/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: Previous studies suggested that patients affected by primary aldosteronism (PA) have impaired quality of life (QOL) compared to the general population, but a direct comparison with patients affected by essential hypertension (EH) has never been performed. The aim of the study was to compare the QOL of patients affected by PA to the QOL of patients affected by EH. MATERIAL AND METHODS: We designed a prospective observational study comparing the QOL of patients with PA and carefully matched patients with EH before and after treatment. We recruited 70 patients with PA and 70 patients with EH, matched for age, sex, blood pressure levels and intensity of antihypertensive treatment. We assessed QOL at baseline and after specific treatment for PA or after optimization of medical therapy for patients with EH. RESULTS: Patients with PA displayed impaired QOL compared with the general healthy population, but similar to patients with EH. Both laparoscopic adrenalectomy and treatment with mineralocorticoid receptor antagonist allowed an improvement of QOL in patients with PA, that was more pronounced after surgical treatment. Optimization of blood pressure control by implementation of antihypertensive treatment (without MR antagonists) allowed a minimal improvement in only one of eight domains in patients with EH. CONCLUSIONS: Patients with PA have impaired QOL, which is likely caused by uncontrolled hypertension and the effects of intensive antihypertensive treatment. Surgical and medical treatment of PA allows a significant improvement of QOL, by amelioration of blood pressure control and, after surgical treatment, by reduction of antihypertensive treatment.
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Hipertensión Esencial/fisiopatología , Hiperaldosteronismo/fisiopatología , Calidad de Vida , Pruebas de Función de la Corteza Suprarrenal , Adrenalectomía , Adulto , Antihipertensivos/uso terapéutico , Hipertensión Esencial/tratamiento farmacológico , Hipertensión Esencial/psicología , Humanos , Hiperaldosteronismo/psicología , Hiperaldosteronismo/terapia , Laparoscopía , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Estudios ProspectivosRESUMEN
BACKGROUND: Decrease in blood pressure (BP) is the major goal of adrenalectomy for primary aldosteronism. Nevertheless, the optimal timing to assess these outcomes and the needed duration of follow-up are uncertain. We systematically reviewed the literature regarding trends in BP-related outcomes during follow-up after adrenalectomy. METHODS: A systematic literature search of medical literature from PubMed, Embase and the Cochrane Library regarding BP-related outcomes (i.e. cure of hypertension rates, BP and antihypertensives) was performed. The Quality In Prognosis Studies risk of bias tool was used. RESULTS: Of the 2057 identified records, 13 articles met the inclusion criteria. Overall study quality was low. In multiple studies, the biggest decrease in BP was shown within the first month(s) after adrenalectomy and afterwards BP often remained stable during long-term follow-up. CONCLUSIONS: Based on the available studies one might suggest that long follow-up is unnecessary, since outcomes seem to stabilize within the first months.
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Adrenalectomía , Hiperaldosteronismo/cirugía , Hipertensión/prevención & control , Antihipertensivos/uso terapéutico , Presión Sanguínea , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/fisiopatología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Resultado del TratamientoRESUMEN
Primary hyperaldosteronism (PA) is the most common cause of secondary arterial hypertension and is frequently undiagnosed. It affects all ages but is more frequent between 20 and 60 years old. The clinical presentation is variable, and the diagnosis is based on screening and, in equivocal cases, confirmatory tests. A 19-year-old student presented with complaints of extreme fatigue, arterial hypertension, hypokalemia and metabolic alkalosis, raising a high index of suspicion for PA. Screening tests were performed and its expressiveness excluded the need of confirmatory tests. CT-scan showed a unilateral adrenal adenoma and the patient was submitted to laparoscopic adenectomy without complications. Prompt diagnosis and treatment are essential to avoid long term complications of PA.
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Neoplasias de la Corteza Suprarrenal , Adrenalectomía/métodos , Adenoma Corticosuprarrenal , Hiperaldosteronismo , Hipertensión , Hipopotasemia , Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Neoplasias de la Corteza Suprarrenal/patología , Adenoma Corticosuprarrenal/diagnóstico por imagen , Adenoma Corticosuprarrenal/patología , Alcalosis/diagnóstico , Alcalosis/etiología , Fatiga/diagnóstico , Fatiga/etiología , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/cirugía , Hipertensión/diagnóstico , Hipertensión/etiología , Hipopotasemia/diagnóstico , Hipopotasemia/etiología , Masculino , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Importance: Most patients with primary aldosteronism, a major cause of secondary hypertension, are not identified or appropriately treated because of difficulties in diagnosis and subtype classification. Applications of artificial intelligence combined with mass spectrometry-based steroid profiling could address this problem. Objective: To assess whether plasma steroid profiling combined with machine learning might facilitate diagnosis and treatment stratification of primary aldosteronism, particularly for patients with unilateral adenomas due to pathogenic KCNJ5 sequence variants. Design, Setting, and Participants: This diagnostic study was conducted at multiple tertiary care referral centers. Steroid profiles were measured from June 2013 to March 2017 in 462 patients tested for primary aldosteronism and 201 patients with hypertension. Data analyses were performed from September 2018 to August 2019. Main Outcomes and Measures: The aldosterone to renin ratio and saline infusion tests were used to diagnose primary aldosteronism. Subtyping was done by adrenal venous sampling and follow-up of patients who underwent adrenalectomy. Statistical tests and machine-learning algorithms were applied to plasma steroid profiles. Areas under receiver operating characteristic curves, sensitivity, specificity, and other diagnostic performance measures were calculated. Results: Primary aldosteronism was confirmed in 273 patients (165 men [60%]; mean [SD] age, 51 [10] years), including 134 with bilateral disease and 139 with unilateral adenomas (58 with and 81 without somatic KCNJ5 sequence variants). Plasma steroid profiles varied according to disease subtype and were particularly distinctive in patients with adenomas due to KCNJ5 variants, who showed better rates of biochemical cure after adrenalectomy than other patients. Among patients tested for primary aldosteronism, a selection of 8 steroids in combination with the aldosterone to renin ratio showed improved effectiveness for diagnosis over either strategy alone. In contrast, the steroid profile alone showed superior performance over the aldosterone to renin ratio for identifying unilateral disease, particularly adenomas due to KCNJ5 variants. Among 632 patients included in the analysis, machine learning-designed combinatorial marker profiles of 7 steroids alone both predicted primary aldosteronism in 1 step and subtyped patients with unilateral adenomas due to KCNJ5 variants at diagnostic sensitivities of 69% (95% CI, 68%-71%) and 85% (95% CI, 81%-88%), respectively, and at specificities of 94% (95% CI, 93%-94%) and 97% (95% CI, 97%-98%), respectively. The validation series yielded comparable diagnostic performance. Conclusions and Relevance: Machine learning-designed combinatorial plasma steroid profiles may facilitate both screening for primary aldosteronism and identification of patients with unilateral adenomas due to pathogenic KCNJ5 variants, who are most likely to show benefit from surgical intervention.
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Hiperaldosteronismo/tratamiento farmacológico , Aprendizaje Automático/tendencias , Esteroides/clasificación , Adulto , Femenino , Humanos , Hiperaldosteronismo/fisiopatología , Masculino , Persona de Mediana Edad , Polonia , Esteroides/uso terapéuticoRESUMEN
CONTEXT: It remains unclear whether adrenalectomy has more beneficial effects than treatment with a mineralocorticoid receptor antagonist on vascular function in patients with aldosterone-producing adenoma (APA). OBJECTIVE: The aim of this study was to compare the effects of adrenalectomy and treatment with eplerenone on vascular function in patients with APA. DESIGN, SETTING, AND PATIENTS: Flow-mediated vasodilation (FMD), as an index of endothelium-dependent vasodilation, and nitroglycerine-induced vasodilation (NID), as an index of endothelium-independent vasodilation, were measured to assess vascular function before and after a 3-month treatment with eplerenone and at 3 months after adrenalectomy in 23 patients with APA. RESULTS: Flow-mediated vasodilation and NID after adrenalectomy were significantly higher than those before treatment with eplerenone (5.4 ± 2.6% vs 2.7 ± 1.9% and 14.8 ± 4.7% vs 9.6 ± 4.6%, P < 0.01, respectively) and those after treatment with eplerenone (5.4 ± 2.6% vs 3.1 ± 2.3% and 14.8 ± 4.7% vs 11.0 ± 5.3%, P < 0.01 and P = 0.03, respectively), while treatment with eplerenone did not alter FMD and NID compared with those before treatment with eplerenone. After adrenalectomy, the increase in FMD and NID were significantly correlated with a decrease in plasma aldosterone concentration and a decrease in the aldosterone-renin ratio. There were no significant relationships between FMD and changes in other parameters or between NID and changes in other parameters. CONCLUSIONS: Adrenalectomy, but not treatment with eplerenone, improved vascular function in patients with APA. Adrenalectomy may be more effective than treatment with eplerenone for reducing the incidence of future cardiovascular events in patients with APA. Clinical Trial Information: URL for the clinical trial: http://UMIN; Registration Number for the clinical trial: UMIN000003409.
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Neoplasias de la Corteza Suprarrenal/terapia , Adrenalectomía , Adenoma Corticosuprarrenal/terapia , Aldosterona/sangre , Endotelio Vascular/fisiopatología , Eplerenona/uso terapéutico , Vasodilatación/fisiología , Neoplasias de la Corteza Suprarrenal/sangre , Neoplasias de la Corteza Suprarrenal/fisiopatología , Adenoma Corticosuprarrenal/sangre , Adenoma Corticosuprarrenal/fisiopatología , Adulto , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Endotelio Vascular/efectos de los fármacos , Eplerenona/administración & dosificación , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/terapia , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Nitroglicerina/administración & dosificación , Vasodilatación/efectos de los fármacosRESUMEN
The physiological stimulation of aldosterone production in adrenocortical glomerulosa cells by angiotensin II and high plasma K+ depends on the depolarization of the cell membrane potential and the subsequent Ca2+ influx via voltage-activated Ca2+ channels. Germline mutations of the low-voltage activated T-type Ca2+ channel CACNA1H (Cav3.2) have been found in patients with primary aldosteronism. Here, we investigated the electrophysiology and Ca2+ signaling of adrenal NCI-H295R cells overexpressing CACNA1H wildtype and mutant M1549V in order to understand how mutant CACNA1H alters adrenal cell function. Whole-cell patch-clamp measurements revealed a strong activation of mutant CACNA1H at the resting membrane potential of adrenal cells. Both the expression of wildtype and mutant CACNA1H led to a depolarized membrane potential. In addition, cells expressing mutant CACNA1H developed pronounced action potential-like membrane voltage oscillations. Ca2+ measurements showed an increased basal Ca2+ activity, an altered K+ sensitivity, and abnormal oscillating Ca2+ changes in cells with mutant CACNA1H. In addition, removal of extracellular Na+ reduced CACNA1H current, voltage oscillations, and Ca2+ levels in mutant cells, suggesting a role of the partial Na+ conductance of CACNA1H in cellular pathology. In conclusion, the pathogenesis of stimulus-independent aldosterone production in patients with CACNA1H mutations involves several factors: i) a loss of normal control of the membrane potential, ii) an increased Ca2+ influx at basal conditions, and iii) alterations in sensitivity to extracellular K+ and Na+. Finally, our findings underline the importance of CACNA1H in the control of aldosterone production and support the concept of the glomerulosa cell as an electrical oscillator.
Asunto(s)
Glándulas Suprarrenales/fisiopatología , Canales de Calcio Tipo T/genética , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Aldosterona/metabolismo , Animales , Células CHO , Calcio/metabolismo , Canales de Calcio Tipo T/metabolismo , Cricetinae , Cricetulus , Humanos , Hiperaldosteronismo/patología , Hiperaldosteronismo/fisiopatología , Potenciales de la Membrana , Mutación , Técnicas de Placa-Clamp , Sodio/metabolismo , Células Tumorales Cultivadas , Zona Glomerular/metabolismo , Zona Glomerular/patología , Zona Glomerular/fisiopatologíaRESUMEN
CONTEXT: Catecholamines and adrenocortical steroids are important regulators of blood pressure. Bidirectional relationships between adrenal steroids and catecholamines have been established but whether this is relevant to patients with pheochromocytoma is unclear. OBJECTIVE: This study addresses the hypothesis that patients with pheochromocytoma and paraganglioma (PPGL) have altered steroid production compared with patients with primary hypertension. DESIGN: Multicenter cross-sectional study. SETTING: Twelve European referral centers. PATIENTS: Subjects included 182 patients with pheochromocytoma, 36 with paraganglioma and 270 patients with primary hypertension. Patients with primary aldosteronism (n = 461) and Cushing syndrome (n = 124) were included for additional comparisons. INTERVENTION: In patients with PPGLs, surgical resection of tumors. OUTCOME MEASURES: Differences in mass spectrometry-based profiles of 15 adrenal steroids between groups and after surgical resection of PPGLs. Relationships of steroids to plasma and urinary metanephrines and urinary catecholamines. RESULTS: Patients with pheochromocytoma had higher (P < .05) circulating concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone, and corticosterone than patients with primary hypertension. Concentrations of cortisol, 11-deoxycortisol, and corticosterone were also higher (P < .05) in patients with pheochromocytoma than with paraganglioma. These steroids correlated positively with plasma and urinary metanephrines and catecholamines in patients with pheochromocytoma, but not paraganglioma. After adrenalectomy, there were significant decreases in cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, aldosterone, and 18-oxocortisol. CONCLUSIONS: This is the first large study in patients with PPGLs that supports in a clinical setting the concept of adrenal cortical-medullary interactions involving an influence of catecholamines on adrenal steroids. These findings could have implications for the cardiovascular complications of PPGLs and the clinical management of patients with the tumors.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/sangre , Glucocorticoides/sangre , Hipertensión/sangre , Paraganglioma/sangre , Feocromocitoma/sangre , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Anciano , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Humanos , Hiperaldosteronismo/etiología , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/cirugía , Hipertensión/etiología , Hipertensión/fisiopatología , Hipertensión/cirugía , Masculino , Persona de Mediana Edad , Paraganglioma/complicaciones , Paraganglioma/fisiopatología , Paraganglioma/cirugía , Feocromocitoma/complicaciones , Feocromocitoma/fisiopatología , Feocromocitoma/cirugía , Estudios RetrospectivosRESUMEN
Primary aldosteronism (PA) represents the leading cause of endocrine hypertension, accounting for 4-13â% of all cases. Simultaneously, it is the most common endocrine form of hypertension that can be cured by surgery. Estimates suggest that 2.5 million people in Germany are affected, yet only 8â% of hypertensive patients undergo the proper diagnostic screening for PA. The diagnosis of PA is evidently not taken into account sufficiently when it comes to the everyday management of hypertension. Since PA patients carry an increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities, early screening and diagnosis is crucial.This manuscript highlights the current guidelines of screening and diagnosing PA and addresses some currently published findings regarding this area. The aim is to raise awareness when it comes to diagnosing and screening for PA in the everyday management of hypertensive patients.
Asunto(s)
Hiperaldosteronismo , Alemania , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatología , Hipertensión , Tamizaje Masivo , Diagnóstico ErróneoRESUMEN
Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.