Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism / 中华内科杂志

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

Advances in Medical Treatment of Primary Aldosteronism / 中国医学科学杂志(英文版)

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Classic and current concepts in adrenal steroidogenesis: a reappraisal

ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a "mineralocorticoid (MC) pathway of zona fasciculata (ZF)", where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme - CYP11B1/CYP11B2 -, responsible for aldosterone formation in ZF under ACTH control, in "type I familial hyperaldosteronism" (dexamethasone suppressible). In "apparent MC excess syndrome", peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the "backdoor pathway", through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.

A retrospective cohort study on the treatment outcome after Unilateral Adrenalectomy among patients with Aldosterone-Producing Adenoma at the University of Santo Tomas Hospital

Background@#Unilateral adrenalectomy is indicated for patients with unilateral primary aldosteronism resulting in normalization of hypokalemia and resolution of hypertension. This study aims to determine the proportion of patients with cure of hypertension and improvement of hypokalemia after unilateral adrenalectomy among patients with aldosterone-producing adenoma and assess the association of preoperative factors with these outcomes.@*Methods@#This is a retrospective cohort study among patients with aldosterone-producing adenoma who underwent unilateral adrenalectomy with at least one month follow-up after the operation. Patients were selected from admissions to the University of Santo Tomas Hospital from January 2008 to November 2018. The proportion of patients with cure of hypertension and resolution of hypokalemia were determined. Binary logistic regression was used to determine preoperative factors associated with these outcomes.@*Results@#Twenty-one patients were included in this study. Cure of hypertension was noted in 47.62% and 42.86% of patients within 24 hours of adrenalectomy and on follow-up, respectively. Improvement of hypokalemia was noted in 61.90% of patients within 24 hours of operation while all patients had improvement of hypokalemia on follow-up. Patients without preoperative hypokalemia were more likely to have cure of hypertension within 24 hours of adrenalectomy (OR=0.0250, p=0.005) and on follow-up (OR=0.0571, p=0.010).@*Conclusion@#Unilateral adrenalectomy results in improvement of hypertension and hypokalemia in the majority of patients with aldosterone-producing adenoma. Shorter duration of hypertension and absence of preoperative hypokalemia were significantly associated with cure of hypertension after unilateral adrenalectomy.

Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Diagnostic value of aldosterone to renin ratio calculated by plasma renin activity or plasma renin concentration in primary aldosteronism: a meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Since the diagnostic value of aldosterone to renin ratio (ARR) calculated by plasma renin concentration (PRC) or plasma renin activity (PRA) is still inconclusive, we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA, so as to provide guidance for clinical diagnosis.@*METHODS@#We searched PubMed, Embase, and Cochrane Library from the establishment of the database to March 2021. We included studies that report the true positive, false positive, true negative, and false negative values for the diagnosis of primary aldosteronism, and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data.@*RESULTS@#The pooled results showed that ARR (plasma aldosterone concentration [PAC]/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78-0.86), a specificity of 0.94 (95% CI: 0.92-0.95), a positive-likelihood ratio (LR) of 12.77 (95% CI: 7.04-23.73), a negative LR of 0.11 (95% CI: 0.07-0.17), and symmetric area under the curve (SAUC) of 0.982, respectively. Furthermore, the diagnostic odds ratio (DOR) of ARR (PAC/PRC) was 180.21. Additionally, the pooled results showed that ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86-0.95), a specificity of 0.91 (95% CI: 0.90-0.93), a positive LR of 7.30 (95% CI: 2.99-17.99), a negative LR of 0.10 (95% CI: 0.04-0.26), and SAUC of 0.976, respectively. The DOR of ARR (PAC/PRA) was 155.52. Additionally, we conducted a subgroup analysis for the different thresholds (<35 or ≥35) of PAC/PRC. The results showed that the DOR of the cut-off ≥35 groups was higher than the cut-off <35 groups (DOR = 340.15, 95% CI: 38.32-3019.66; DOR = 116.40, 95% CI = 23.28-581.92).@*CONCLUSIONS@#The research results suggest that the determination of ARR (PAC/PRC) and ARR (PAC/PRA) was all effective screening tools for PA. The diagnostic accuracy and diagnostic value of ARR (PAC/PRC) are higher than ARR (PAC/PRA). In addition, within a certain range, the higher the threshold, the better the diagnostic value.

Persistent and serious hyperkalemia after surgery of primary aldosteronism: A case report / 北京大学学报(医学版)

Hyperkalemia was one of the complications after primary aldosteronism surgery. Hyperkalemia after primary aldosteronism surgery was uncommon in clinical practice, especially persistent and serious hyperkalemia was rare. This complication was not attached great importance in clinical work. A case about persistent and serious hyperkalemia after primary aldosteronism adrenal adenoma surgery was reported and the patient was followed-up for fourteen months in this study. This patient had a laparoscopic adrenalectomy due to primary aldosteronism. Hyperkalemia was detected one month after surgery of this patient, the highest level of plasma potassium was 7.0 mmol/L. The patient felt skin itchy, nausea, palpitation. Plasma aldosterone concentration fell to 2.12 ng/dL post-operation from 35.69 ng/dL pre-operation, zona glomerulosa insufficiency was confirmed by hormonal tests in this patient after surgery. And levels of 24 hours urinary potassium excretion declined. Decrease of aldosterone levels after surgery might be the cause of hyperkalemia. Hyperkalemia lasted for 14 months after surgery and kalemia-lowering drugs were needed. A systemic search with "primary aldosteronism", "hyperkalemia", "surgical treatment" was performed in PubMed and Wanfang Database for articles published between January 2009 and December 2019. Literature review indicated that the incidence of hyperkalemia after primary aldosteronism surgery was 6% to 29%. Most of them was mild to moderator hyperkalemia (plasma potassium 5.5 to 6.0 mmol/L) and transient. 19% to 33% in hyperkalemia patients was persistent hyperkalemia. Previous studies in the levels of plasma potassium reached the level as high as 7 mmol/L in our case were rare. Whether hypoaldosteronemia was the cause of hyperkalemia was not consistent in the published studies. Risk factors of hyperkalemia after primary aldosteronism surgery included kidney dysfunction, old age, long duration of hypertention. This paper aimed to improve doctors' aweareness of hyperkalemia complication after primary aldosteronism surgery. Plasma potassium should be monitored closely after primary aldosteronism surgery, especially in the patients with risk factors. Some patients could have persistent and serious hyperkalemia, and need medicine treatment.

Hipertensão resistente em paciente com diagnótico de hiperaldosteronismo primário: resposta ao eplerenone / Resistant hypertension in a patient with primary hypereraldosteronism diagnosis: response to eplerenone

A maioria dos pacientes com hipertensão arterial (HA) não tem etiologia clara e é classificada como hipertensão primária. No entanto, 5% a 10% desses pacientes podem ter hipertensão secundária, o que indica presença de uma causa subjacente e potencialmente reversível. Em adultos com 65 anos ou mais, estenose da artéria renal aterosclerótica, insuficiência renal e hipotireoidismo são causas comuns. A hipertensão secundária deve ser considerada na presença de sintomas e sinais sugestivos, como hipertensão grave ou resistente, idade de início inferior a 30 anos (especialmente antes da puberdade), hipertensão maligna ou acelerada e aumento agudo da pressão arterial a partir de leituras previamente estáveis. Outras causas subjacentes da hipertensão secundária incluem hiperaldosteronismo, apneia obstrutiva do sono, feocromocitoma, síndrome de Cushing, doença da tireoide, coarctação da aorta e uso de certos medicamentos. A hipertensão arterial resistente (HAR) é definida quando a pressão arterial (PA) permanece acima das metas recomendadas com o uso de três anti-hipertensivos de diferentes classes, incluindo um bloqueador do sistema renina- -angiotensina (inibidor da enzima conversora da angiotensina [IECA] ou bloqueador do receptor de angiotensina [BRA]), um bloqueador dos canais de cálcio (BCC) de ação prolongada e um diurético tiazídico (DT) de longa ação em doses máximas preconizadas e toleradas, administradas com frequência, dosagem apropriada e comprovada adesão. Hipertensão arterial acompanhada de supressão da atividade da renina plasmática (ARP) e aumento da excreção de aldosterona caracteriza a síndrome de aldosteronismo primário. Esse quadro foi descrito, pela primeira vez em 1955 por Conn, em um paciente hipertenso grave hipocalêmico e com secreção elevada de aldosterona, que submetido à adrenalectomia direita resultou em cura da HA

Patients with arterial hypertension have no clear etiology and are classified as primary hypertension. However, 5% to 10% of these with hypertension may have the secondary form of disease, which indicates the presence of an underlying and potentially reversible cause. In adults aged 65 and over, the common causes of secondary hypertension are atherosclerotic renal artery stenosis, renal failure and hypothyroidism. Secondary hypertension should be considered in the presence of suggestive symptoms and signs, such as severe or resistant hypertension, age at onset less than 30 years (especially before puberty), malignant or accelerated hypertension and acute increase in blood pressure from previously stable readings. Other underlying causes of secondary hypertension include hyperaldosteronism, obstructive sleep apnea, pheochromocytoma, Cushing's syndrome, thyroid disease, coarctation of the aorta and use of others medications. Resistant arterial hypertension is defined when blood pressure remains above the recommended targets with the use of three antihypertensives of different classes, including a blocker of the renin-angiotensin system (inhibitor of the angiotensin-converting enzyme or angiotensin receptor blocker ), a calcium channel blocker and a thiazide diuretic in maximum recommended and tolerated doses, administered frequently, appropriate dosage and proven adherence. Arterial hypertension accompanied by suppression of plasma renin activity and increased aldosterone excretion characterizes the primary aldosteronism syndrome. This condition was described in 1955 by Conn, in a severe hypohypokalemic hypertensive patient with high aldosterone secretion, who underwent right adrenalectomy resulted in a cure for the hypertension

Chronic kidney disease after adrenalectomy in a patient with primary aldosteronism / 北京大学学报(医学版)

We report one case of estimated glomerular filtration rate (eGFR) decline after taking unilateral adrenalectomy due to aldosterone adenoma. A 60-year-old male with 23-year history of hypertension was reported to the endocrinologist due to hypokalemia (serum potassium 3.01 mmol/L). Urine microalbumin/creatinine (ALB/CR) was 70.15 mg/g, serum creatinine was 82 μmol/L and eGFR was 89.79 mL/(min·1.73 m2). Random serum aldosterone was 172.2-203.5 ng/L, and random plasma rennin activity was 0-0.17 μg/(L·h). His captopril challenge test suggested that his aldosterone le-vels were suppressed by 8% (< 30%) and the adrenal enhanced computed tomography scan revealed a left adrenal tumor. The patient was diagnosed with primary hyperaldosteronism (PA), aldosterone adenoma and underwent left laparoscopic adrenalectomy. Histological examination confirmed adrenal cortical adenoma. One week after the operation, his serum creatinine was increased to 127 μmol/L compared with preoperative level; eGFR was 32.34 mL/(min·1.73 m2). His systolic blood pressure (SBP) was 110 mmHg and diastolic blood pressure (DBP) was 60 mmHg (hypotensive drugs discontinued), and serum potassium level was 5.22 mmol/L. At the end of the 2-year follow up, the serum creatinine of this patient remained at 109-158 μmol/L and eGFR fluctuated from 63.28-40.12 mL/(min·1.73 m2). PA is one of the most common causes of secondary hypertension. Several studies have reported renal function deterioration of PA patients after unilateral adrenalectomy, like the patient in this article. Age, preoperative plasma aldosterone concentration, albuminuria and preoperative potassium level might be significant predictors of a decrease in the eGFR. Growing evidence suggests that aldosterone could contribute to structural kidney damage, arterial injury and hemodynamic disorder. At the same time, patients with PA exhibit glomerular hyperfiltration and glomerular vascular hypertension, leading to the misinterpretation of renal function in PA patients as subtle kidney damage may be masked by the glomerular hyperfiltration before treatment. After a unilateral adrenalectomy, glomerular hyperfiltration by aldosterone excess is resolved and renal damage can be unmasked. In conclusion, kidney function deterioration after adrenalectomy can be detected in some patients with PA. Thus, accurate evaluation of kidney function in patients with PA may be essential, especially for those with preoperative risk factors for postoperative renal impairment. After unilateral adrenalectomy, close monitoring of renal function and adequate management are required for PA patients.

Advance in Surgical Treatment for Primary Aldosteronism / 中国医学科学院学报

Primary aldosteronism is the most common cause of secondary hypertension.This review focuses on the procedures related to surgical treatment and summarizes the available evidence.We analyzed the impact of primary aldosteronism on the body,the advantages of surgical treatment,the choice of patients and surgical methods,perioperative management,and surgical efficacy evaluation.Finally,we put forward the prospect of scientific research in this field,with a view to providing reference for clinical work.

Hipertensión Arterial Secundaria ¿por dónde empezar? / Secondary Arterial Hypertension, where to start?

30 to 40% of the adult population worldwide has been diagnosed with hypertension, among these patients 5 to 10% of them could have a possibly curable condition. In order to recognize this special population, the clinician must perform a complete work up and be aware of the main underlying causes of secondary hypertension. Often this could be a goal difficult to accomplish. The purpose of this article is to discuss the most frequent causes of secondary hypertension and offer a diagnostic approach for these patients. Clinicians should never forget that drug-related hypertension is a common cause that is discovered only with the help of a good medical history.

Polimiopatia hipocalêmica e hipertensão secundária a hiperaldosteronismo primário felino / Hypokalemic polymyopathy and secondary hypertension to feline primary hyperaldosteronism

O hiperaldosteronismo se define pela hipersecreção de aldosterona pelas suprarrenais, resultando em excesso de sódio e redução de potássio sanguíneo. Esta hipersecreção deve-se à síntese autônoma de aldosterona por células adrenais hiperplásicas ou neoplásicas, que agem independentemente da estimulação pelo sistema renina-angiotensina. A doença acomete felinos de adultos maduros a idosos. O excesso de aldosterona culmina em hipertensão sistêmica e/ou hipocalemia, que levam à fraqueza muscular e alterações oculares. O diagnóstico é baseado em exames laboratoriais e de imagem, e o tratamento pode ser clínico ou cirúrgico. O prognóstico é considerado favorável quando as medicações são capazes de melhorar as manifestações clínicas ou quando é possível realizar o procedimento cirúrgico. O presente trabalho visa relatar o caso de um felino macho de 13 anos, castrado, sem raça definida, com hipocalemia persistente secundária a um presuntivo tumor adrenal.

Hyperaldosteronism is defined by the hypersecretion of aldosterone by the adrenal glands resulting in excess sodium and reduced blood potassium. This hypersecretion is due to the autonomous synthesis of aldosterone by hyperplastic or neoplastic adrenal cells, which act independently of stimulation by the renin-angiotensin system. The disease affects felines in the age group from mature adults to the elderly. The excess of aldosterone culminates in systemic hypertension and/or hypokalemia, which leads to muscle weakness and ocular changes. The diagnosis is based on laboratory and imaging tests and treatment can be clinical or surgical. The prognosis is considered favorable when the medications are able to improve the clinical manifestations or when it is possible to perform the surgical procedure. The present paper aims to report the case of a 13-year-old male cat, castrated, crossbred, with persistent hypokalemia secondary to a presumptive adrenal tumor.

Polimiopatia hipocalêmica e hipertensão secundária a hiperaldosteronismo primário felino / Hypokalemic polymyopathy and secondary hypertension to feline primary hyperaldosteronism

O hiperaldosteronismo se define pela hipersecreção de aldosterona pelas suprarrenais, resultando em excesso de sódio e redução de potássio sanguíneo. Esta hipersecreção deve-se à síntese autônoma de aldosterona por células adrenais hiperplásicas ou neoplásicas, que agem independentemente da estimulação pelo sistema renina-angiotensina. A doença acomete felinos de adultos maduros a idosos. O excesso de aldosterona culmina em hipertensão sistêmica e/ou hipocalemia, que levam à fraqueza muscular e alterações oculares. O diagnóstico é baseado em exames laboratoriais e de imagem, e o tratamento pode ser clínico ou cirúrgico. O prognóstico é considerado favorável quando as medicações são capazes de melhorar as manifestações clínicas ou quando é possível realizar o procedimento cirúrgico. O presente trabalho visa relatar o caso de um felino macho de 13 anos, castrado, sem raça definida, com hipocalemia persistente secundária a um presuntivo tumor adrenal.

Hyperaldosteronism is defined by the hypersecretion of aldosterone by the adrenal glands resulting in excess sodium and reduced blood potassium. This hypersecretion is due to the autonomous synthesis of aldosterone by hyperplastic or neoplastic adrenal cells, which act independently of stimulation by the renin-angiotensin system. The disease affects felines in the age group from mature adults to the elderly. The excess of aldosterone culminates in systemic hypertension and/or hypokalemia, which leads to muscle weakness and ocular changes. The diagnosis is based on laboratory and imaging tests and treatment can be clinical or surgical. The prognosis is considered favorable when the medications are able to improve the clinical manifestations or when it is possible to perform the surgical procedure. The present paper aims to report the case of a 13-year-old male cat, castrated, crossbred, with persistent hypokalemia secondary to a presumptive adrenal tumor.

Hiperaldosteronismo primario en una población de pacientes hipertensos / Primary hyperaldosteronism in a population of hypertensive patients

El diagnóstico de hiperaldosteronismo primario (HPAP) aumentó en los últimos años y algunos autores lo consideran la principal causa de hipertensión arterial secundaria. Estudiamos la prevalencia de HPAP en el total de pacientes hipertensos atendidos en la Unidad de Hipertensión Arterial, en el período comprendido entre julio 1999 a julio 2017. Se incluyeron 2500 pacientes y en 79 se diagnosticó HPAP (3.2%). El HPAP fue más frecuente en mujeres (55.7%), observándose un incremento en la edad geriátrica con relación a estudios previos (27.8%). El diagnóstico se sospechó ante la presencia de kaliuria inapropiada y alcalosis metabólica, acompañada de un cociente aldosterona/actividad de renina plasmática superior a 30 (ng/dl)/(ng/ ml/h). Tras su confirmación se realizaron estudios de imagen para determinar la etiología. Se detectaron así 29 casos (36.8%) de adenomas productores de aldosterona y 5 de hiperplasia bilateral suprarrenal con nódulos. La tomografía computarizada identificó el 100% de los adenomas y de las hiperplasias con nódulos corticales bilaterales. El tratamiento con suprarrenalectomía y/o antialdosterónicos resultó eficaz en el control de la presión arterial en el 69.9% de los casos. Se comentan aspectos particulares de esta serie, como la remisión de la insuficiencia renal, la elevada presencia de litiasis urinaria hipercalciúrica y la detección de un carcinoma de mama tras dosis prolongadas de espironolactona.

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/o r 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.

Surgical outcomes of laparoscopic adrenalectomy for primary hyperaldosteronism: 20 years of experience in a single institution

PURPOSE: Recently, posterior retroperitoneoscopic adrenalectomy (PRA) has been reported to have some advantages over laparoscopic transperitoneal adrenalectomy (LTA). The objectives of this study were to report our experience over 12 years with laparoscopic adrenalectomy for primary hyperaldosteronism (PHA) and to examine surgical outcomes of PRA compared with LTA in patients with PHA. METHODS: The medical records of 527 patients who underwent minimally invasive adrenalectomy, including LTA or PRA, from January 2006 until May 2017 were reviewed at Severance Hospital (Seoul, Korea). Clinicopathologic characteristics and surgical outcomes of 146 patients with PHA who underwent LTA (19 patients) or PRA (127 patients) were analyzed retrospectively by complete chart review. RESULTS: The overall rates of biochemical and clinical cure were 91.1% and 93.1%, respectively. The mean operation time of the PRA group was significantly shorter than that of the LTA group (72.3 ± 24.1 minutes vs. 115.7 ± 69.7 minutes, P = 0.015). The length of hospital stay in the PRA group was significantly shorter than in the LTA group (3.5 ± 1.3 days vs. 4.2 ± 1.6 days, P = 0.029), and the first meal after surgery came earlier in the PRA group (0.3 ± 0.5 days vs. 0.6 ± 0.5 days, P = 0.049). The number of pain-killers used was also significantly smaller in the PRA group (2.3 ± 2.1 vs. 4.3 ± 2.3, P < 0.001). CONCLUSION: PRA offers an alternative or likely superior method for treatment of small adrenal diseases such as PHA, with improved surgical outcomes.

Rabdomiólisis por hipopotasemia severa en paciente con síndrome de Conn / Rhabdomyolysis and profound hypokalemia in a patient with Conn´s syndrome

El Síndrome de Conn o hiperaldosteronismo primario se caracteriza por hipertensión, hipopotasemia con alcalosis metabólica y una masa adrenal. La rabdomiólisis puede ser secundaria a traumatismos, excesiva actividad muscular, enfermedades musculares hereditarias y otras causas médicas, como la hipopotasemia. Presentamos el caso de un hombre de 46 años con rabdomiólisis secundaria e hipopotasemia severa como expresión de hiperaldosteronismo primario por un adenoma suprarrenal(AU)

Conn's syndrome or primary hyperaldosteronism is characterized by hypertension, hypokalemia with metabolic alkalosis and the presence of an adrenal mass. Rhabdomyolysis can be secon- dary to trauma, excessive muscle activity, hereditary muscle diseases and other medical causas, such as hypokalemia. We present the case of a 46-year-old man with secondary rhabdomyolisis and hypokalemia as an-expresión of primary hyperaldosteronism due to an adrenal adenoma(AU)

Systemic hormonal unloading in unilateral adrenalectomy in a patient with bilateral adrenal hyperplasia: A case report

Background @#Unilateral adrenalectomy has not been recommended in the guidelines as a treatment for primary hyperaldosteronism secondary to bilateral adrenal hyperplasia (BAH). Interestingly, recent studies have shown that increased circulation of aldosterone increased oxidative stress, cardiovascular (CV) complications such as atrial fi brillation, myocardial infarction and heart failure; and that unilateral adrenalectomy led to improved CV function. Therefore, recognizing the role of unilateral adrenalectomy in BAH, specifi cally for improved quality of life is important.@*Clinical case@# A 47‐year-old hypertensive (highest blood pressure [BP] 150/90 mmHg) woman had a severe headache, muscle weakness, polyuria, and polydipsia. Her serum potassium (K) was low at 3.1 mmol/L (3.5–5 mmol/L). Initial tests showed elevated plasma aldosterone, suppressed plasma renin activity and elevated aldosterone-renin ratio (6.61 ng/ dL, <0.1 ng/mL and 66, respectively). Plasma aldosterone after saline suppression test (12.70 ng/dL) confi rmed the diagnosis of primary aldosteronism (PA). MRI showed a well-defi ned, oval-shaped solid nodule in the medial limb of the left adrenal gland (1.8 x 1.2 cm). Bilateral adrenal vein sampling with adrenocorticotropic hormone (ACTH) stimulation test was compatible with BAH (cortisol-corrected aldosterone ratio pre-ACTH stimulation 1.29 and postACTH 1.66), with dominant aldosterone secreting left adrenal gland (7200 vs 3760 ng/dL). She was started on spironolactone 200 mg/day and amlodipine 10 mg/day and eventually shifted to eplerenone. Despite the optimal dose of eplerenone and amlodipine, she still experienced severe headaches, palpitations and breakthrough elevations of BP that led to her recurrent admissions. Eplerenone was shifted back to spironolactone (150-200 mg/day) with amlodipine dose (10 mg/day) normalizing her blood pressure and potassium level, yet with persistent headache and muscle weakness. Repeat imaging using CT scan with contrast showed consistent results. Postoperatively, with all medications discontinued the patient was asymptomatic, normotensive (110/70 mmHg) and normokalemic (4.0 mmol/L). One month later, her BP started to increase again at 140/80 mmHg and her K decreased to 3.4 mmol/L. Normalization of said parameters (BP:120/70 mmHg K: 4.1 mmol/L), with stabilization following lower doses of amlodipine (5mg/day) and spironolactone (25 mg/day). Also, all the symptomatology of the patient resolved completely.@*Conclusion@#This present case exemplifi es a unilateral adrenalectomy approach in BAH, which led to improvement in BP and K levels, despite low medication doses. Furthermore, symptom relief and improved quality of life, as desired outcomes, were achieved.

Molecular Mechanisms of Primary Aldosteronism

Primary aldosteronism (PA) results from excess production of mineralocorticoid hormone aldosterone by the adrenal cortex. It is normally caused either by unilateral aldosterone-producing adenoma (APA) or by bilateral aldosterone excess as a result of bilateral adrenal hyperplasia. PA is the most common cause of secondary hypertension and associated morbidity and mortality. While most cases of PA are sporadic, an important insight into this debilitating disease has been derived through investigating the familial forms of the disease that affect only a minor fraction of PA patients. The advent of gene expression profiling has shed light on the genes and intracellular signaling pathways that may play a role in the pathogenesis of these tumors. The genetic basis for several forms of familial PA has been uncovered in recent years although the list is likely to expand. Recently, the work from several laboratories provided evidence for the involvement of mammalian target of rapamycin pathway and inflammatory cytokines in APAs; however, their mechanism of action in tumor development and pathophysiology remains to be understood.

Resistant Hypertension: A Clinical Case / Hipertensión resistente: un caso clínico / Hipertensão resistente: um caso clínico

Abstract Introduction: Secondary hypertension corresponds to 15 % of the causes of arterial hypertension, and among them, primary hyperaldosteronism presents a variable incidence of about 3 % in hypertensive patients. It has a slightly higher prevalence in women, between 30 and 60 years, and is usually unilateral. Case presentation: The authors describe the clinical case of a patient, followed by a severe hypertension medicated with four antihypertensive drugs for tension stabilization, maintaining systolic arterial tensions superior to 170 mmHg. In the aetiological study of hypertension, analytical alterations suggested hyperaldosteronism and a nodular lesion was detected in the left adrenal gland. The patient was submitted to surgery and excision of the lesion was done with histological confirmation of the diagnosis of corticomedullary adenoma of the adrenal gland. The patient presented improvement of the tension profile, with need to suspend two of the four antihypertensive drugs and to reduce the dose of the remaining ones. Conclusion: A tumor of the adrenal cortex producing aldosterone is the main cause of primary hyperaldosteronism and should always be excluded when the presence of difficult to control, severe hypertension is detected, since the standard treatment is surgical, leading to a stabilization of the tension pattern after a few months.

Resumen Introducción: la hipertensión secundaria corresponde al 15 % de las causas de hipertensión arterial, y entre ellas, el hiperaldosteronismo primario presenta una incidencia variable de sobre 3 % en pacientes hipertensos. Tiene una prevalencia ligeramente mayor en mujeres, entre 30 y 60 años, y generalmente es unilateral. Presentación del caso: los autores describen el caso clínico de un paciente, seguido por una hipertensión resistente medicada con cuatro fármacos antihipertensivos para la estabilización de la tensión, con mantenimiento de las tensiones arteriales sistólicas superiores a 170 mmHg. Las alteraciones analíticas en el estudio etiológico de la hipertensión sugirieron hiperaldosteronismo y una lesión nodular en la glándula suprarrenal izquierda. El paciente fue sometido a cirugía y se realizó la escisión de la lesión con confirmación histológica del diagnóstico de adenoma corticomedular de la glándula suprarrenal. El paciente presentó una mejora en el perfil de tensión, con la necesidad de suspender dos de los cuatro fármacos antihipertensivos y reducir la dosis de los restantes. Discusión: un tumor de la corteza suprarrenal que produce la aldosterona es la principal causa de hiperaldosteronismo primario y siempre debe excluirse cuando se presenta hipertensión grave, difícil de controlar, ya que el tratamiento estándar es quirúrgico y conduce a una estabilización del patrón de tensión después de unos meses.

Resumo Introdução: a hipertensão secundária corresponde ao 15 % das causas de hipertensão arterial, e entre elas, o hiperaldosteronismo primário apresenta uma incidência variável de sobre 3 % em pacientes hipertensos. Tem uma prevalência ligeiramente maior em mulheres, entre 30-60 anos, e geralmente é unilateral. Apresentação do caso: os autores descrevem o caso clínico de um paciente, seguido por uma hipertensão resistente medicada com quatro fármacos anti-hipertensivos para a estabilização da tensão, com manutenção das tensões arteriais sistólicas a 170 mmHg. As alterações analíticas no estudo etiológico da hipertensão sugeriram hiperaldosteronismo e uma lesão nodular na glândula suprarrenal esquerda. O paciente foi submetido a cirurgia e se realizou a incisão da lesão com confirmação histológica do diagnóstico de adenoma córtico-medular da glândula suprarrenal. O paciente apresentou uma melhora no perfil de tensão, com a necessidade de suspender dois dos quatro fármacos anti-hipertensivos e reduzir a dose dos restantes. Discussão: um tumor do córtex suprarrenal que produz a aldosterona é a principal causa de hiperaldosteronismo primário e sempre deve excluir-se quando se apresenta hipertensão grave, difícil de controlar, pois o tratamento standard é cirúrgico e conduz a uma estabilização do patrão de tensão depois de uns meses.