Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma / 中华内科杂志

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2<PRC≤4 mU/L. PRC was not suppressed (PRC>8.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Hipertensión secundaria: ¿cuándo y cómo buscarla? / Secondary hypertension: when and how to look for it?

Resumen En la población hipertensa se detecta una causa subyacente en 5% a 10%. Identificar etiología y establecer un tratamiento específico reduce el riesgo de daño de órgano blanco y, en algunos casos, puede curar la enfermedad primaria y la hipertensión. Dada su baja prevalencia, no se recomienda realizar una búsqueda exhaustiva de causas secundarias en todos los pacientes hipertensos. En este artículo se analiza cuándo y cómo debe estudiarse una hipertensión secundaria.

Abstract In the hypertensive population, between 5-10%, an underlying cause is detected. Identifying the etiology and giving specific treatment reduces the risk of hypertension-mediated organ damage and, in some cases, can cure the disease and high blood pressure. Due to its low prevalence, an exhaustive search for secondary causes is not recommended in all patients with hypertension. This article will discuss when and how to study secondary hypertension.

Clinical application of 68Ga-pentixafor PET/CT in surgical diagnosis and prognosis evaluation of primary aldosteronism and correlation analysis of clinical prognosis / 中华泌尿外科杂志

Objective:To explore the clinical value of 68Ga-pentixafor PET/CT targeting for CXCR4 in the diagnosis and prognosis evaluation of primary aldosteronism (PA). Methods:Retrospective analysis was performed on information of 72 patients diagnosed with PA who received operations according to the results of 68Ga-pentixafor PET/CT in our hospital. There were 37 males and 35 females, with the average age of (48.3±9.5) years old. The average lesion diameter was (1.60 ± 0.54)cm. The preoperative systolic and diastolic blood pressure were (177.3 ± 23.9)mmHg and (107.6 ± 13.2)mmHg, respectively. The average preoperative potassium level was (2.62 ± 0.56)mmol/L. The average aldosterone concentration was (17.98 ± 4.66)ng/dl, and the median plasma renin activity was 0.01 (0.01, 0.09) ng/(ml·h). All patients underwent 68Ga-pentixafor PET/CT examination, which lead to the decision of surgical strategies. For those patients with single lesion, multiple lesions in one side or positive lesion in one side but negative in the opposite side, surgical resection of the positive side lesion or total adrenalectomy was considered. For those patients with bilateral positive lesions, surgical resection of the side with more significant positive lesions or total adrenalectomy was considered. For those with negative multiple lesions, the surgical strategy was designed according to the results of CT examination or AVS. The positive rate of 68Ga-pentixafor PET/CT and its relationship with the clinical characteristics and prognosis of patients were analyzed. Results:The results of 68Ga-pentixafor PET/CT were positive in 62 of 72 patients diagnosed with PA (86.1%), and the median SUVmax value was 11.1 (7.1, 16.2). The SUVmax value was positively correlated with the maximum diameter of adrenal lesion ( r=0.468) and negatively correlated with blood potassium levels ( r=-0.437), while not significantly correlated with other clinical characteristics. The positive rate of adenoma by 68Ga-pentixafor PET/CT was higher than that of nodular hyperplasia [90.5%(57/63) vs. 55.6%(5/9), P=0.018], and the SUVmax value in adenoma was also higher than that in nodular hyperplasia [11.9(7.8, 16.2) vs. 4.3(3.4, 11.3), P=0.022]. 32 cases were cured after operations, and 37 cases were improved. And 3 cases were not cured. The SUVmax value of lesions in the cured patients was higher than that in the improved patients [15.4(8.1, 22.7) vs. 10.1(6.8, 13.3), P=0.013]. Among 59 cases of PA patients with single adrenal lesions, 50 cases represented positive results of 68Ga-pentixafor PET/CT. 23 cases in 50 positive cases were cured and 27 cases were improved after resection of positive lesions. In the 13 PA patients with multiple adrenal lesions who underwent surgery according to the results of 68Ga-pentixafor PET/CT, 12 patients (92.3%) showed postoperative prognosis in line with preoperative expectations. Conclusions:68Ga-pentixafor PET/CT showed high positive rate in the diagnosis of PA, especially for adenoma.The SUVmax value of the adrenal lesion was correlated with the blood potassium level, the size of the lesion and the postoperative prognosis. In addition, 68Ga-pentixafor PET/CT could effectively guide the surgical decision of PA.

Atractylenolide-I covalently binds to CYP11B2, selectively inhibits aldosterone synthesis, and improves hyperaldosteronism

Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11B2 (CYP11B2), an important enzyme in aldosterone (ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1. In this study, atractylenolide-I (AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2, leading to the suppression of ALD synthesis; AT-I shows a significant therapeutic effect for improving hyperaldosteronism.

Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism / 中华内科杂志

Objective:The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA).Methods:This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy.Results:A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUC ROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions:CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

The research progress in surgical treatment of primary hyperaldosteronism / 中华泌尿外科杂志

Surgery is the first choice for patients with primary hyperaldosteronism diagnosed with aldosterone-producing adenoma and unilateral adrenal hyperplasia.The objective of surgical treatment is to excise the adrenal aldosterone hypersecretion tissue and improve the prognosis. However, the choice of partial adrenalectomy or total adrenalectomy is still controversial. In this paper, the efficacy, safety, postoperative cortisol level, postoperative recurrence and surgical techniques of primary hyperaldosteronism subtypes treated by different surgical methods were discussed.

HIPERTENSI SEKUNDER: GEN-GEN YANG MERANGSANG PEREMBESAN ALDOSTERON YANG BERLEBIHAN (SECONDARY HYPERTENSION: GENES THAT STIMULATE EXCESSIVE SECRETION OF ALDOSTERONE) / Jurnal Sains Kesihatan Malaysia

@#Hypertension is highly prevalent in Malaysia and even the rest of the world. Primary aldosteronism (PA) is one of the most common treatable cause of secondary hypertension. PA occurs due to excessive secretion of aldosterone in the adrenal glands. Up to one in five resistant hypertension cases are due to PA. Therefore, there are a high number of individuals who have the potential to be cured of their hypertension. However, this is difficult to achieve due to limitations in the procedure of diagnosing the PA disease. The challenge now is to know the best usage of available diagnostic methods to detect those who would most likely be cured of hypertension which may be associated with the genotype of the disease. In the past decade, five genes have been found to cause excess aldosterone production in aldosteroneproducing adenomas (APAs), namely KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1. These somatic mutations have been found to activate the intracellular signaling pathway that regulates aldosterone production. Studies on bilateral adrenal hyperplasia (BAH) samples also have identified the genetic causes for the many hereditary hyperaldosteronism, namely familial hyperaldosteronism types I, II, III, and IV/V. Herein we review the genetic factors of PA as a result of either aldosterone-stimulating somatic mutations or germline variants, and the associated clinical phenotype.

Tratamiento del hiperaldosteronismo primario durante el embarazo: reporte de un caso / Management of primary hyperaldosteronism during pregnancy: Case report

Resumen ANTECEDENTES: El hiperaldosteronismo primario es la principal causa de hipertensión arterial de origen endocrino en la población general; su manifestación durante el embarazo es poco frecuente, casi siempre provocado por un adenoma adrenal productor de aldosterona. De 1962 a la fecha se han descrito alrededor de 50 casos. Objetivo: Reportar un caso de hiperaldosteronismo durante el embarazo y revisar la bibliografía relacionada. CASO CLÍNICO: Paciente de 39 años, con antecedente médico de hipertensión arterial, en curso del segundo trimestre del quinto embarazo, que acudió a consulta por hipertensión no controlada e hipocalemia. El tratamiento incluyó un antagonista del receptor de aldosterona, que permitió el control de la tensión arterial y la finalización del embarazo. Posteriormente se identificó un nódulo adrenal, cuya resección resultó en normalización de las concentraciones de aldosterona, la actividad de renina plasmática, calemia y remisión de la hipertensión hasta la actualidad. CONCLUSIÓN: Las recomendaciones para el tratamiento de pacientes con hiperaldosteronismo durante el embarazo se basan en los casos publicados y los datos de toxicidad generados de estudios en animales. De ahí la importancia de este caso, que aporta información importante y puede considerarse en situaciones similares.

Abstract BACKGROUND: Primary hyperaldosteronism is the main cause of arterial hypertension of endocrine origin in the general population; its presentation during pregnancy is infrequent; having described about 50 cases since 1962, the most common cause is the presence of an adrenal adenoma. OBJECTIVE: To report the first case of hyperaldosteronism treated during pregnancy in Peru and reviews the literature. CLINICAL CASE: A 39-year-old patient with a history of arterial hypertension and poor obstetric history, who was referred to our center in the second trimester of the 5th pregnancy due to uncontrolled hypertension and symptomatic hypokalemia. Management included an aldosterone receptor antagonist, allowing the control of blood pressure and the culmination of the pregnancy with the delivery of a healthy girl. Subsequently, the presence of an adrenal nodule was confirmed, the resection of which resulted in normalization of aldosterone concentration, plasma renin activity, kalemia, and remission of hypertension to date. CONCLUSION: Recommendations on the management of hyperaldosteronism during pregnancy are based only on published cases and drug toxicity data were generated in animal studies. Hence the importance of this report, which provides information that can be considered in similar situations.

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.

Clinical value of captopril test in noninvasive diagnosis of aldosterone-producing adenoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA.@*METHODS@#The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA.@*RESULTS@#Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%.@*CONCLUSION@#ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

Clinical features of endocrine diseases complicated with rhabdomyolysis / 西安交通大学学报(医学版)

Objective: To investigate the clinical and laboratory characteristics of endocrine diseases complicated with rhabdomyolysis (RM). Methods: We made a retrospective analysis of clinical features, diagnosis and treatment of 10 cases of endocrine diseases induced RM among 144 RM patients admitted to The First Affiliated Hospital of Xi'an Jiaotong University from June 2008 to May 2019. Results: Primary hypothyroidism was the most common endocrine etiology leading to RM. Other etiologies included diabetic ketosis, hyperglycemic hyperosmolar syndrome, diabetic nephropathy, hyperaldosteronism and Cushing syndrome. The onset of RM caused by endocrine diseases was insidious, lacking the typical triad of myalgia, muscle weakness and colored urine. Complications such as acute kidney injury and multiple-organ dysfunction syndrome were less common in RM caused by endocrine diseases. These patients seldom needed continuous renal replacement therapy, and good prognosis could be attained via routine fluid infusion and alkalization treatment. Conclusion: Many endocrine diseases can cause RM and their clinical manifestations are often atypical. Clinicians should be vigilant for early identification. Treatment should be comprehensive to improve the prognosis.

Resistant and refractory hypertension: two sides of the same disease? / Hipertensão resistente e refratária: duas faces de uma mesma doença?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.

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.

Hipertensão arterial resistente (HAR) / Resistant arterial hypertension (RAH)

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. Nesta definição está incluído o subgrupo de pacientes hipertensos resistentes, cuja PA é controlada com quatro ou mais medicamentos anti-hipertensivos, chamada de HAR controlada (HAR-C). A classificação da doença em HAR-C e HAR não controlada (HAR-NC), incluindo a HAR refratária (HAR-Ref), um fenótipo extremo de HAR-NC em uso de cinco ou mais anti-hipertensivos, é uma proposta que ganha espaço na literatura. Diante da suspeita clínica de HAR, é necessário verificar a confirmação diagnóstica, e a primeira etapa na investigação é a exclusão das causas de pseudorresistência, tais como falta de adesão ao tratamento (farmacológico e não farmacológico), posologia inadequada, técnica imprópria de aferição da PA e efeito do avental branco. O MAPA e o monitoramento residencial da pressão arterial (MRPA) são os exames para confirmação do controle inadequado da PA. Uma vez afastada a pseudorresistência, confirma-se a existência da HAR e inicia-se uma investigação diagnóstica com exames específicos, conforme a orientação das Diretrizes de Hipertensão em relação ao comprometimento de lesões em órgãos-alvo e hipertensão secundária. A ocorrência de comorbidades associadas deve ser detectada com exames especializados de acordo com a suspeita clínica. O objetivo do tratamento medicamentoso na HAR é detectar as causas do não controle e encontrar a melhor combinação de fármacos, visando o alcance das metas pressóricas com menor ocorrência de efeitos adversos e maior adesão. Em geral, busca-se otimizar o tratamento tríplice com os fármacos preferenciais, que são: IECA ou BRA, BCC di-hidropiridínico e DT.

Resistant hypertension (RHTN) is defined as blood pressure (BP) persistently above the recommended target values despite the use of three antihypertensive agents of different classes, including one blocker of the renin- angiotensin system (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]), one long- acting calcium channel blocker (CCB), and one long-acting thiazide diuretic (TD) at maximum recommended and tolerated doses, administered with appropriate frequency and doses and with proven adherence. The definition above includes a subgroup of patients with RHTN whose BP is controlled with four or more antihypertensive medications, known as controlled RHTN (C-RHTN). On clinical suspicion of RHTN, diagnostic confirmation is required, and the first step in the investigation is the exclusion of causes of pseudoresistance, such as lack of treatment adherence (pharmacological and non-pharmacological), inadequate dosing, improper BP measurement technique, and white-coat effect. Lack of BP control should be confirmed by ABPM and home blood pressure monitoring (HBPM). Secondary hypertension (SecH) is defined as increased BP due to an identifiable cause. Patients with RH should be investigated for the most prevalent causes of "non-endocrine" and "endocrine" SecH after exclusion of use of medications that may interfere with BP values: antiinflammatory drugs, glucocorticoids, nasal decongestants, appetite suppressants, antidepressants, immunosuppressants, erythropoietin, contraceptives, and illicit drugs. The objective of pharmacological treatment in RHTN is to identify the causes of lack of control and find the best combination of drugs, aiming at achieving the target BP with few adverse effects and greater adherence. In general, triple treatment optimization is attempted with preferred drugs, namely, ACEIs or ARBs, dihydropyridine CCBs, and TDs

Hipertensión arterial secundaria a hiperaldosteronismo primario / Hypertension secondary to primary hyperaldosteronism

RESUMEN La hipertensión arterial es una afección pandémica responsable de varias complicaciones cardiovasculares, neurológicas y renales. La gran mayoría se debe a la hipertensión esencial o primaria, pero cada vez se diagnostican más casos de hipertensión arterial secundaria, ya sea de causa endocrinológica, renal o neurológica. Se presenta un caso de hipertensión secundaria a hiperaldosteronismo primario.

ABSTRACT Hypertension is a pandemic worldwide, being responsible for several cardiovascular, neurological and renal complications. The vast majority is due to essential or primary hypertension, but more and more cases of secondary arterial hypertension are diagnosed, either due to endocrinological, renal or neurological causes. Next, an hypertension case of secondary to primary hyperaldosteronism is presented.

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)

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.

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.

Comparison of the ratio of plasma aldosterone to renin concentrationmeasured by two chemiluminescent immunoassays in screening for primary aldosteronism / 中华内分泌外科杂志

Objective@#To compare the detection efficiency of the ratio of plasma aldosterone concentration to renin concentration (ARR) measured by imported and domestic chemiluminescent immunoassay kits for screening primary aldosteronism (PA) .@*Methods@#A total of 164 patients with essential hypertension and 64 patients with PA were recruited in this study. Plasma aldosterone concentration (PAC) and renin concentration (PRC) were measured concurrently by imported chemiluminescent immunoassay kit (Diasorin, Italy) and domestic kit (Mindray, Shenzhen, China) , and then ARR were calculated. A ROC curve analysis was performed to compare the screening efficacy of the two kits and the optimal ARR cut-offs for PA screening were recommended according to Youden’s index.@*Results@#The areas under the ROC curves (AUCROC) of ARR were 0.937 (95% CI 0.897-0.965, P<0.0001) detected by imported kit and 0.942 (95% CI 0.903-0.968, P<0.0001) detected by domestic kit. The difference of AUCROC of ARR detected by two kits was 0.00457 (95% CI -0.0210-0.0302, P<0.7263) .The highest Youden’s indexes of ARR were 0.749 (detected by imported kit) with the cut-off value of 12.8 (pg/ml) / (μIU/ml) (sensitivity 96.87%, specificity 78.05%) and 0.756 (detected by domestic kit) with the cut-off value of 12.5 (pg/ml) / (μIU/ml) (sensitivity 89.06%, specificity 86.59%) .@*Conclusions@#There was no significant difference between domestic and imported chemiluminescent immunoassays in the screening efficiency of ARR for PA.