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1.
J Pharm Biomed Anal ; 207: 114423, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34670179

RESUMO

The accurate quantification of aldosterone (ALD) in adrenal tributary venous serum/plasma collected by a super-selective adrenal venous sampling (ssAVS) technique has become a definitive procedure to identify the forms (laterality) of primary aldosteronism (PA) and the location of the affected segment(s), and to subsequently make the treatment decision. In this study, a stable isotope-dilution LC/ESI-MS/MS-based method was developed and validated for the determination of the ALD concentrations of the six ssAVS serum samples during a single run. A sextet of Girard reagents was used to convert ALD to the derivatives having different masses for each sample. Based on the validation tests, satisfactory specificity, precision and accuracy were observed and the matrix effect was found to be acceptable. The developed method was used for the analysis of the ssAVS serum samples from eight PA patients. The batch analysis of the six samples permitted the direct comparison of the ALD concentrations between the samples and enhanced to determine the laterality and location of the affected segment(s). The total analysis time after the sample purification was also reduced to 1/3 for the 24 samples by the sample-sextuplex procedure, which was also an advantage of the developed method.


Assuntos
Aldosterona , Espectrometria de Massas em Tandem , Betaína/análogos & derivados , Cromatografia Líquida , Humanos
2.
Int J Cardiol ; 345: 54-60, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34728260

RESUMO

BACKGROUND: Although renin-angiotensin-aldosterone system (RAAS) activation is believed to be the major driver of acute heart failure (AHF) episodes our understanding of its prevalence and clinical relevance in contemporary settings is incomplete. METHODS: Serum renin and aldosterone were measured at day-1 and at discharge in patients (n = 211) that were hospitalized between 2016 and 2017 for AHF in a single cardiology center. The population was profiled based on upper limits of normal (ULN) of both biomarkers assessed at day-1 and linked with the clinical course and outcomes. RESULTS: The study population constituted of three profiles: RAAS-/- (n = 121 [57%]); RAAS+/- (n = 60 [28%]); and RAAS+/+ (n = 30 [14%]). The RAAS+/+ profile had the lowest blood pressure and serum sodium at admission, day-2 and discharge compared to the other profiles (p < 0.001). The RAAS+/+ patients had significantly lower urine Na+ at admission (57.8 ± 36.7 vs 97.3 ± 31.3 and 86.4 ± 35.0), day-1 (52.7 ± 32.7 vs 85.3 ± 36.3 and 75.5 ± 33.9) mmol/l, vs RAAS-/- and RAAS+/- profiles, respectively, all p < 0.001. There was also a gradual decrease of renal function across increasing RAAS profiles. The RAAS+/+ profile received higher dose of furosemide at discharge 120 [80-160] vs the other profiles 80 [40-120] mg, p < 0.01. The risks of one year mortality or HF rehospitalization increased across the RAAS profiles (p < 0.001). The trajectory of renin or aldosterone change during hospitalization was not related to outcomes. CONCLUSIONS: The RAAS overactivity is not essential for development of AHF. However, elevated RAAS is a marker of more advanced stages of heart failure, is related to low natriuresis and adverse clinical outcomes.


Assuntos
Aldosterona , Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Humanos , Rim/fisiologia , Prognóstico , Renina
3.
Cardiovasc Ther ; 2021: 1710731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786023

RESUMO

Background: A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective: To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods: Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results: 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions: Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.


Assuntos
Aldosterona , Infarto do Miocárdio , Humanos , Masculino , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Volume Sistólico , Função Ventricular Esquerda
4.
Diagn Interv Radiol ; 27(6): 754-761, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34792030

RESUMO

PURPOSE: We aimed to analyze the prevalence and radiological characteristics of duplicated right adrenal veins (DRAVs) and evaluate the diagnostic impact of adrenal venous sampling (AVS) in primary aldosteronism. METHODS: DRAVs were retrospectively identified among patients who underwent segmental AVS between April 2017 and March 2020. DRAVs were defined as main or accessory according to the drainage area. The diameter, position, hormone levels, and treatment plan based on AVS were compared between main and accessory RAVs, using the Wilcoxon rank-sum test. RESULTS: Fourteen of 432 patients (3.2%) were diagnosed with DRAVs. On venography, the mean diameters of the main and accessory side were 3±0.63 mm and 2.1±0.41 mm, respectively, and were significantly different (p < 0.001). The mean relative position in craniocaudal direction of main and accessory veins from the adrenal caudal edge on computed tomography was 65.5%±16.0%, and 48.1%±16.8%, respectively, which was significantly different (p = 0.007). The left-right positions and hormone levels were not significantly different. Based on conventional AVS, the treatment plan between DRAVs was not changed in six of eight patients, but changed from surgery to medication in two patients with right aldosterone-producing adenoma (APA)/microadenoma based on segmental AVS findings. CONCLUSION: DRAVs, in which the main RAV was thicker and more cranially located than the accessory RAV were rare. Depending on blood sampled from either of DRAVs, the diagnosis made through conventional AVS might change treatment approach from surgery to medication, especially with right APA. Hence, their identification is important to make an accurate subtyping by AVS.


Assuntos
Adenoma Adrenocortical , Hiperaldosteronismo , Glândulas Suprarrenais/diagnóstico por imagem , Aldosterona , Humanos , Hiperaldosteronismo/diagnóstico por imagem , Estudos Retrospectivos
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 890-894, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622611

RESUMO

The patient, a 41-year-old woman, was admitted because "it was found out she had elevated serum potassium levels for 18 days". Eighteen days prior to admission at our hospital, the patient was found to have elevated serum potassium during hospitalization at another hospital, where the patient received symptomatic treatment and was discharged after her serum potassium returned to a normal level. However, the patient still had elevated serum potassium repeatedly and was referred to our hospital for further examination. The patient had a history of acute nephritis and gestational hypertension. Six months prior to admission at our hospital, it was found out that the patient had slightly elevated blood pressure, but no intervention was done. The patient's father has a history of hypertension and diabetes. After admission, laboratory results showed that the patient had hyperkalemia, hyperchloremia and metabolic acidosis. The level of plasma renin was obviously below the normal range, but the concentration of plasma aldosterone was within the normal range. A new mutation locus (c.1115delG) in KLHL3 (Kelch like family member 3) gene was revealed by genetic testing, leading to the diagnosis of pseudoaldosteronism type Ⅱ (PHA2). The patient was given regular treatment of oral hydrochlorothiazide hydrochloride at set intervals. Subsequently, her blood electrolyte level, blood pH, BE and BEB have returned to normal levels. The patient was followed up for 12 months and did not feel unwell during the follow-up period.


Assuntos
Hipertensão , Pseudo-Hipoaldosteronismo , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Aldosterona , Feminino , Humanos , Proteínas dos Microfilamentos , Mutação , Potássio , Pseudo-Hipoaldosteronismo/diagnóstico , Pseudo-Hipoaldosteronismo/genética
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(9): 996-1002, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34707010

RESUMO

OBJECTIVES: Adrenal venous sampling (AVS) is one of the recognized effective methods for the identification of primary aldosteronism, and the success rate is related to the skill level of the operator. This study aims to analyze the learning curve of AVS and to determine the number of staged cases of AVS procedure success rate, and to provide a reference for the standardized use of AVS. METHODS: The age, gender, blood pressure, surgery success rate, operation time, radiation dose, and operation-related complications of 120 patients with primary aldosteronism who underwent continuous AVS in the Second Xiangya Hospital from August 2015 to February 2021 were retrospectively collected. The cumulative sum analysis was used to analyze the learning curve of the operator. The minimum cases who were proficient in the operation was determined according to the learning curve, and the patients were divided into 4 groups a, b, c, and d according to the time sequence of receiving AVS based on the cut-off point. The AVS success rate, radiation dose, operation time, and complications of each group were analyzed. RESULTS: The cumulative sum analysis showed that the learning curves were divided into a learning stage and a mastery stage with 30 cases as the cut-off point, and the operation experience of the surgeon was from raw to mature. The success rates of the a, b, c, and d groups were 66.7%, 86.7%, 93.3%, and 96.7%, respectively. Compared with b, c, and d groups, the success rate in group a was significant decreased (all P<0.05), the operative time in group a was significantly lengthened (all P<0.05), and the radiation dose in group a was significantly increased (all P<0.05). CONCLUSIONS: After accumulating the AVS experience of 30 cases of primary aldosteronism, the operation time is obviously shortened, the radiation dose is significantly decreased, the operative complications are significantly reduced, and the learning curve enters a plateau. In the future, the success rate of AVS procedure may be improved through further standardized training.


Assuntos
Hiperaldosteronismo , Curva de Aprendizado , Glândulas Suprarrenais , Aldosterona , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Estudos Retrospectivos
7.
Med Clin North Am ; 105(6): 1047-1063, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688414

RESUMO

Adrenal masses are frequently incidentally identified from cross-sectional imaging studies, which are performed for other reasons. The intensity of the approach to the patient with such a mass is tailored to the clinical situation, ranging from a quick evaluation to a detailed work-up. In all cases, the three components of the evaluation are clinical assessment, review of the images, and biochemical testing with the goal of ruling out malignancy and identifying hormonally active lesions. This article incorporates recent information to produce a logical, systematic assessment of these patients with risk stratification and proportionate follow-up.


Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico , Doenças das Glândulas Suprarrenais/patologia , Adenoma/diagnóstico por imagem , Adenoma/patologia , Doenças das Glândulas Suprarrenais/sangue , Doenças das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Aldosterona/biossíntese , Catecolaminas/biossíntese , Diagnóstico Diferencial , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/patologia , Achados Incidentais , Feocromocitoma/diagnóstico , Feocromocitoma/patologia
8.
Med Clin North Am ; 105(6): 1065-1080, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688415

RESUMO

Hyperaldosteronism is a relatively more common disorder than previously recognized. Patients with hyperaldosteronism are at high risk for cardiovascular events. Patients suspected of having hyperaldosteronism should undergo initial screening and subsequent confirmatory testing to establish a biochemical diagnosis. Although adrenal computed tomography/magnetic resonance imaging scans often define a disease's subtype, adrenal vein sampling, in order to determine lateralization, may be necessary in some patients who are surgical candidates. Medical therapy using optimal doses of mineralocorticoid receptor antagonists can control symptoms and normalize plasma renin activity. The long-term outcome of patients treated with either surgical or optimal medical therapy appears similar.


Assuntos
Aldosterona/metabolismo , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Aldosterona/sangue , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Renina/metabolismo , Sistema Renina-Angiotensina/fisiologia
9.
Am J Physiol Renal Physiol ; 321(5): F645-F655, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605273

RESUMO

Fine tuning of Na+ reabsorption takes place along the aldosterone-sensitive distal nephron, which includes the collecting duct (CD), where it is mainly regulated by aldosterone. In the CD, Na+ reabsorption is mediated by the epithelial Na+ channel and Na+ pump (Na+-K+-ATPase). Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-8 is one of the main tight junction proteins expressed along the aldosterone-sensitive distal nephron. We have previously shown a coupling between transcellular Na+ reabsorption and paracellular Na+ barrier. We hypothesized that aldosterone controls the expression levels of both transcellular Na+ transporters and paracellular claudin-8 in a coordinated manner. Here, we show that aldosterone increased mRNA and protein levels as well as lateral membrane localization of claudin-8 in cultured CD principal cells. The increase in claudin-8 mRNA levels in response to aldosterone was prevented by preincubation with 17-hydroxyprogesterone, a mineralocorticoid receptor antagonist, and by inhibition of transcription with actinomycin D. We also showed that a low-salt diet, which stimulated aldosterone secretion, was associated with increased claudin-8 abundance in the mouse kidney. Reciprocally, mice subjected to a high-salt diet, which inhibits aldosterone secretion, or treated with spironolactone, a mineralocorticoid receptor antagonist, displayed decreased claudin-8 expression. Inhibition of glycogen synthase kinase-3, Lyn, and Abl signaling pathways prevented the effect of aldosterone on claudin-8 mRNA and protein abundance, suggesting that signaling of protein kinases plays a permissive role on the transcriptional activity of the mineralocorticoid receptor. This study shows that signaling via multiple protein kinases working in concert mediates aldosterone-induced claudin-8 expression in the CD.NEW & NOTEWORTHY In this study, we showed that aldosterone modulates claudin-8 expression in cultured collecting duct principal cells and in the mouse kidney. The upregulation of claudin-8 expression in response to aldosterone is dependent on at least glycogen synthase kinase-3, Lyn, and Abl signaling pathways, indicating the participation of multiple protein kinases to the effect of aldosterone.


Assuntos
Aldosterona/farmacologia , Claudinas/metabolismo , Túbulos Renais Coletores/efeitos dos fármacos , Reabsorção Renal/efeitos dos fármacos , Sódio/metabolismo , Animais , Linhagem Celular , Claudinas/genética , Dieta Hipossódica , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Camundongos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Sódio na Dieta/toxicidade , Transcrição Genética , Regulação para Cima , Quinases da Família src/genética , Quinases da Família src/metabolismo
10.
Zhonghua Yi Xue Za Zhi ; 101(34): 2662-2666, 2021 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-34510871

RESUMO

Primary aldosteronism (PA) patients diagnosed with aldosterone-producing adenoma and unilateral adrenal hyperplasia are preferred for surgical treatment.The aim of the operation is to remove the hypersecretory aldosterone tissue of adrenal and to improve the prognosis.Current studies have shown that both partial adrenalectomy and total adrenalectomy can achieve clinical cure for PA, but the choice of surgical methods is still controversial. This paper discusses the efficacy and safety, postoperative changes in cortisol level, postoperative recurrence and surgical techniques of different surgical methods in the treatment of different PA subtypes, so as to find the best surgical methods for different PA subtypes and to maximize the benefits for patients.


Assuntos
Adenoma , Hiperaldosteronismo , Adenoma/cirurgia , Glândulas Suprarrenais , Adrenalectomia , Aldosterona , Humanos , Hiperaldosteronismo/cirurgia , Recidiva Local de Neoplasia
11.
Zhonghua Yi Xue Za Zhi ; 101(34): 2667-2673, 2021 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-34510872

RESUMO

Objective: To explore related factors associated with unilateral aldosterone secretion of patients with primary aldosteronism (PA) and construct a predictive model. Methods: The clinical data of patients who were diagnosed as PA in West China Hospital from April 2016 to September 2020 was analyzed retrospectively. According to the results of the adrenal enhancement CT, patients were divided into 3 groups, namely non-nodular group with no bilateral adrenal glands lesions, only with unilateral adrenal hyperplasia or bilateral adrenal hyperplasia, unilateral nodule group with unilateral adrenal nodules and the contralateral adrenal glands with hyperplasia or not, and bilateral nodules group with nodules in both adrenal glands. Regarding the related factors of dominant side of aldosterone secretion, univariate analysis and binary logistic regression were used. Receiver operating characteristic curve and nomogram were used to evaluate the diagnostic performance of regression models. Results: A total of 237 patients with PA were included, of which, 118 males and 119 females, the median age was 39 years, and the body mass index (BMI) was (25.2±3.5) kg/m2. There were 157 (66.2%) of 237 patients with typical imaging findings. There were 32 cases in no-nodular group, 183 cases in unilateral nodule group, and 22 cases in bilateral nodules group. Multivariate analysis showed that age (OR=0.876, P<0.001), blood potassium concentration (OR=0.430, P=0.004), and typical imaging findings (OR=2.202, P=0.035) were associated with unilateral aldosterone secretion. As for unilateral nodule group, multivariate analysis showed that age (OR=0.900, P<0.001), plasma aldosteronism concentration (PAC) (OR=1.050, P=0.018), and typical imaging findings (OR=2.637, P=0.025) were associated with unilateral aldosterone secretion. The agreement rate between the dominant side of the adrenal CT and AVS was only 50.2%. Multivariate analysis showed that age (OR=0.954, P=0.001), BMI (OR=0.893, P=0.024) and PAC (OR=1.043, P=0.011) were independently associated with concordance between AVS and CT. The cut-off value of the ROC curve was 0.43; the model sensitivity was 56.3%; the specificity was 86.7% and the area under the ROC curve was 0.742. Conclusions: Age is an important predictor in the diagnosis of PA subtypes. It is recommended to refer to subgroup based on imaging results for clinical decision. For patients with no obvious lesions or bilateral lesions on CT, AVS should be performed as far as possible to confirm the subtypes in diagnosis of PA.


Assuntos
Aldosterona , Hiperaldosteronismo , Glândulas Suprarrenais , Adulto , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Masculino , Curva ROC , Estudos Retrospectivos
12.
Zhonghua Yi Xue Za Zhi ; 101(34): 2681-2685, 2021 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-34510874

RESUMO

Objective: To explore the potential application of a three-dimensional visualization technique in adrenal vein sampling (AVS). Methods: The clinical data were retrospectively analyzed, which included 76 patients with primary aldosteronism (PA) who have undergone AVS in Guizhou Provincial People's Hospital from December 2017 to May 2020. All cases were examined by adrenal thin-section enhanced CT and blood was drawn by bilateral AVS. Among them, the adrenal vein blood of 46 cases was sampled with the help of three-dimensional (3D) visualization processing of CT data, while that of 30 cases was without 3D visualization processing. The rate of the catheter in place, the successful rate of AVS, the time of blood collection, the dosage of the contrast agent, and surgical complications were compared between the two groups. Results: There were 76 cases included, while 38 were male and 38 were female. The average age was 45 (25-57) years. Compared with the patients without the aid of 3D visualization, the success rate of right AVS of the patients with the aid of 3D visualization technology increased from 43% to 78% (P<0.05). The success rate of adrenal vein blood collection increased from 53% to 83%. The dose of contrast agent decreased [the M(Q1,Q3) were78 (59, 89) ml vs 28 (16, 51) ml, P<0.05], and the time of blood sampling from the right adrenal vein approximately decreased [the M(Q1,Q3) were 70 (66, 88) min vs 44 (22, 61) min, P<0.05]. Compared with the case without the aid of 3D visualization, the left adrenal vein catheterization rate of patients in the 3D visualization group increased from 97% to 98%, the success rate of adrenal vein blood collection increased from 97% to 98%, and the differences of the time of blood sampling and the dosage of the contrast were not statistically significant between the two groups. Among all the cases experienced bilateral AVS, only one patient without 3D reconstruction had contrast extravasation, and the others had no obvious complications. Conclusions: Before AVS, 3D visualization processing of adrenal vein from CT data is capable of increasing the success rate of blood sampling from the right adrenal vein, as well as reducing the dosage of contrast agent and the time of adrenal vein blood sampling. Therefore, it has a potential clinical value of the application.


Assuntos
Hiperaldosteronismo , Imageamento Tridimensional , Glândulas Suprarrenais/diagnóstico por imagem , Aldosterona , Coleta de Amostras Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Vet Intern Med ; 35(5): 2159-2166, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34473866

RESUMO

BACKGROUND: Primary hyperaldosteronism caused by adrenal neoplasia has been well described in cats. Multiple corticosteroid abnormalities occur in a subset of affected cats, but characterizations of this syndrome are limited to several case reports. OBJECTIVES: To describe a series of cats with adrenal tumors secreting aldosterone and additional corticosteroids. ANIMALS: Ten cats with multiple corticosteroid secreting adrenocortical tumors. METHODS: Retrospective case series. Medical records of cats with adrenal tumors secreting both aldosterone and progesterone were identified. Data concerning historical findings, clinicopathologic features, treatments, and outcomes were retrieved from medical records. RESULTS: All 10 cats had diabetes mellitus in addition to biochemical features of hyperaldosteronism such as hypokalemia. High corticosterone concentrations were observed in all 3 cats in which this corticosteroid was measured. Ultrasound examinations revealed unilateral adrenal tumors in all 10 cases, and the contralateral adrenal gland was either atrophied or not identified in 5 cats. Three of 4 cats developed hypoadrenocorticism after surgical adrenalectomy. Three cats achieved diabetic remission after adrenalectomy. Two cats treated with adrenalectomy survived >1 year, 1 cat survived 6.5 months, and 1 cat was alive 5.5 months after diagnosis. Survival >1 year occurred in 2 of 4 cats treated with medical management alone. Two cats were not treated. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of multiple corticosteroid abnormalities should be considered in cats with aldosterone secreting adrenal tumors, especially those with concurrent diabetes mellitus. Both surgical and medical management can result in long-term survival, although diabetic remission was documented only in cats undergoing adrenalectomy.


Assuntos
Neoplasias das Glândulas Suprarrenais , Doenças do Gato , Hiperaldosteronismo , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/veterinária , Glândulas Suprarrenais/diagnóstico por imagem , Adrenalectomia/veterinária , Aldosterona , Animais , Gatos , Hiperaldosteronismo/cirurgia , Hiperaldosteronismo/veterinária , Progesterona , Estudos Retrospectivos
15.
Int J Mol Sci ; 22(17)2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34502527

RESUMO

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood-retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone-an MR-specific agonist, or cortisol or cortisol + RU486-a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial-mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.


Assuntos
Aldosterona/metabolismo , Hidrocortisona/metabolismo , Células-Tronco Pluripotentes/metabolismo , Receptores de Mineralocorticoides/metabolismo , Doenças Retinianas/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Animais , Transição Epitelial-Mesenquimal , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Humanos , Camundongos , Camundongos Transgênicos , Células-Tronco Pluripotentes/patologia , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/genética , Doenças Retinianas/genética , Doenças Retinianas/patologia , Epitélio Pigmentado da Retina/patologia
16.
S Afr J Surg ; 59(3): 131a-131c, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34515436

RESUMO

SUMMARY: Primary aldosteronism, eponymously known as Conn's syndrome, has recently gained recognition as the most common cause of endocrine hypertension. Unilateral subtypes, such as aldosterone secreting adenomas, are managed surgically and are potentially curable. The background of refractory hypertension and hypokalaemia in a forty-year-old man raised suspicions of Conn's syndrome which was localised to an aldosterone secreting adenoma in the right adrenal gland. The patient underwent a laparoscopic intraperitoneal right adrenalectomy which resulted in normalisation of his plasma aldosterone concentration as well as improved blood pressure control.


Assuntos
Adenoma , Hiperaldosteronismo , Hipertensão , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/cirurgia , Adrenalectomia , Adulto , Aldosterona , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/cirurgia , Hipertensão/diagnóstico , Hipertensão/etiologia , Masculino
17.
Int J Mol Sci ; 22(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34502509

RESUMO

Excess aldosterone promotes pathological remodeling of the heart and imbalance in cardiac ion homeostasis of sodium, potassium and calcium. Novel treatment with proanthocyanidins in aldosterone-treated rats has resulted in downregulation of cardiac SGK1, the main genomic aldosterone-induced intracellular mediator of ion handling. It therefore follows that proanthocyanidins could be modulating cardiac ion homeostasis in aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg-1 day-1) +1% NaCl for three weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg-1 day-1). PRO80 prevented cardiac hypertrophy and decreased calcium content. Expression of ion channels (ROMK, NHE1, NKA and NCX1) and calcium transient mediators (CAV1.2, pCaMKII and oxCaMKII) were reduced by PRO80 treatment in aldosterone-treated rats. To conclude, our data indicate that PRO80 may offer an alternative treatment to conventional MR-blockade in the prevention of aldosterone-induced cardiac pathology.


Assuntos
Insuficiência Cardíaca/metabolismo , Hipertensão/metabolismo , Proantocianidinas/metabolismo , Aldosterona/metabolismo , Aldosterona/farmacologia , Animais , Cardiomegalia/metabolismo , Coração/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Homeostase/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Canais Iônicos/metabolismo , Masculino , Miocárdio/metabolismo , Proantocianidinas/fisiologia , Ratos , Ratos Wistar
18.
Cells ; 10(9)2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34572026

RESUMO

Adrenal steroid hormone production is a dynamic process stimulated by adrenocorticotropic hormone (ACTH) and angiotensin II (AngII). These ligands initialize a rapid and robust gene expression response required for steroidogenesis. Here, we compare the predominant human immortalized cell line model, H295R cell, with primary cultures of adult adrenocortical cells derived from human kidney donors. We performed temporally resolved RNA-seq on primary cells stimulated with either ACTH or AngII at multiple time points. The magnitude of the expression dynamics elicited by ACTH was greater than AngII in primary cells. This is likely due to the larger population of adrenocortical cells that are responsive to ACTH. The dynamics of stimulus-induced expression in H295R cells are mostly recapitulated in primary cells. However, there are some expression responses in primary cells absent in H295R cells. These data are a resource for the endocrine community and will help researchers determine whether H295R is an appropriate model for the specific aspect of steroidogenesis that they are studying.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Aldosterona/metabolismo , Transcriptoma/efeitos dos fármacos , Angiotensina II/metabolismo , Células Cultivadas , Humanos , Hidrocortisona/metabolismo
19.
Curr Opin Pharmacol ; 60: 216-225, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34474209

RESUMO

Growing evidencehas described a correlation between aldosterone, obesity, and insulin resistance, suggesting that adipocyte-related factors and mineralocorticoid receptor (MR) overactivation may alter aldosterone secretion, potentially leading to obesity and glucose intolerance. Preclinical studies showed that pharmacological antagonism of MR prevents white adipose tissue dysfunction(s) and expansion, activates brown adipose tissue, and improves glucose tolerance. The clinical use of nonsteroidal MR antagonists has been shown to reduce the risk of diabetic kidney disease progression and cardiovascular events in patients with diabetes. This review aims to summarize the effects of pharmacological MR blockade on obesity and its associated metabolic comorbidities, with a particular focus on the therapeutic implications of nonsteroidal MR antagonists in the management of patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo Marrom , Aldosterona , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Receptores de Mineralocorticoides
20.
Biochem Med (Zagreb) ; 31(3): 030902, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34393596

RESUMO

Introduction: It is common for patients to switch between several healthcare providers. In this context, the long-term follow-up of medical conditions based on laboratory test results obtained from different laboratories is a challenge. The measurement uncertainty in an inter-laboratory context should also be considered in data mining research based on routine results from randomly selected laboratories. As a proof-of-concept study, we aimed at estimating the inter-laboratory reference change value (IL-RCV) for exemplary analytes from publicly available data on external quality assessment (EQA) and biological variation. Materials and methods: External quality assessment data of the Reference Institute for Bioanalytics (RfB, Bonn, Germany) for serum creatinine, calcium, aldosterone, PSA, and of whole blood HbA1c from campaigns sent out in 2019 were analysed. The median CVs of all EQA participants were calculated based on 8 samples from 4 EQA campaigns per analyte. Using intra-individual biological variation data from the EFLM database, positive and negative IL-RCV were estimated with a formula based on log transformation under the assumption that the analytes under examination have a skewed distribution. Results: We estimated IL-RCVs for all exemplary analytes, ranging from 13.3% to 203% for the positive IL-RCV and - 11.8% to - 67.0% for the negative IL-RCV (serum calcium - serum aldosterone), respectively. Conclusion: External quality assessment data together with data on the biological variation - both freely available - allow the estimation of inter-laboratory RCVs. These differ substantially between different analytes and can help to assess the boundaries of interoperability in laboratory medicine.


Assuntos
Análise Química do Sangue/normas , Técnicas de Laboratório Clínico , Mineração de Dados/métodos , Aldosterona/sangue , Cálcio/sangue , Creatinina/sangue , Coleta de Dados , Tomada de Decisões , Desenho de Equipamento , Hemoglobina A Glicada/biossíntese , Humanos , Modelos Teóricos , Antígeno Prostático Específico/sangue , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes
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