scholarly journals Treatment of Primary Aldosteronism and Organ Protection

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Cristiana Catena ◽  
GianLuca Colussi ◽  
Leonardo A. Sechi
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Organ Damage ◽  
Secondary Hypertension ◽  
Renal Protection ◽  
Organ Protection ◽  
Unilateral Adrenalectomy ◽  
Renal Complications ◽  
Aldosterone Producing Adenoma ◽  
The Impact

Primary aldosteronism is a frequent form of secondary hypertension that had long been considered relatively benign. Experimental and clinical evidence collected in the last two decades, however, has clearly demonstrated that this endocrine disorder is associated with excess cardiovascular and renal complications as compared to essential hypertension. These complications reflect the ability of inappropriate elevation of plasma aldosterone to cause tissue damage beyond that induced by high blood pressure itself, thereby setting the stage for major cardiovascular and renal disease. Because of the impact of elevated aldosterone on organ damage, goals of treatment in patients with primary aldosteronism should not be limited to normalization of blood pressure, and prevention or correction of organ complications is mandatory. Treatment with mineralocorticoid receptor antagonists or unilateral adrenalectomy is the respective options for treatment of idiopathic adrenal hyperplasia or aldosterone-producing adenoma. Last years have witnessed a rapid growth in knowledge concerning the effects of these treatments on cardiovascular and renal protection. This paper is an overview of the cardiovascular and renal complications that occur in patients with primary aldosteronism and a summary of the results that have been obtained in the long term on cardiovascular and renal outcomes with either medical or surgical treatment.

scholarly journals SAT-558 A Dedicated Endocrine Hypertension Service Increases the Timely Diagnosis of Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jun Yang ◽  
Yin Y Lim ◽  
Renata Libianto ◽  
Jimmy Shen ◽  
Morag Jennifer Young ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Care ◽  
Primary Aldosteronism ◽  
Pressure Control ◽  
Organ Damage ◽  
Antihypertensive Medications ◽  
Endocrine Hypertension ◽  
Treatment Naïve ◽  
Hypertension Diagnosis ◽  
The Impact

Abstract Background: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk that could be averted with targeted treatment. An Endocrine Hypertension Service (EHS), encompassing an education program, streamlined diagnostic tests and dedicated PA clinic, was developed to address this issue. Aims: To analyse the impact of Victoria’s first dedicated EHS on the pattern of PA diagnoses. Methods: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (N=267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2), and Year 3 (Y3), based on their first visit. Results: The proportion of referrals from primary care increased (20% in Y1 to 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1 to 19% in Y3). Patients with a hypertension diagnosis of 5 years or less at the time of referral to EHS increased from 34% in Y1 to 45% in Y3 whilst the percentage of patients with a hypertension diagnosis of more than 10 years decreased from 50% in Y1 to 35% in Y3. Consistent with an earlier presentation, the proportion of patients with end-organ damage at the time of referral decreased from 44% in Y1 to 29% in Y3. Almost a third of the PA patients had unilateral disease; all of those who underwent adrenalectomy had biochemical cure. Patients with bilateral PA were treated with spironolactone. Their systolic/diastolic blood pressure decreased by 15/12 mmHg in Y1, 17/13 mmHg in Y2 and 23/11 mmHg in Y3; while the mean number of antihypertensive medications decreased from 2.9 to 1.8 in Y1, 2.7 to 2.0 in Y2 and 2.2 to 1.6 in Y3 Conclusion: The EHS has facilitated an increase in referrals for PA screening from primary care, resulting in the earlier diagnosis of PA, when less complications are present, and optimised patient outcomes. A broader uptake of such a clinical service, integrated with education outreach, will bridge the gap between the reported high prevalence of PA and the actual low diagnostic rates.

scholarly journals A case of primary aldosteronism with a negative aldosterone-to-renin ratio

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fengyi Liu ◽  
Liang Wang ◽  
Yanchun Ding
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Antihypertensive Drugs ◽  
Target Organ Damage ◽  
Screening Method ◽  
Organ Damage ◽  
Secondary Hypertension ◽  
Cardiovascular Damage ◽  
Aldosterone To Renin Ratio ◽  
Clinical Conditions

Abstract Background Primary aldosteronism (PA), as a cause of secondary hypertension, can cause more serious cardiovascular damage than essential hypertension. The aldosterone-to-renin ratio (ARR) is recommended as the most reliable screening method for PA, but ARR screening is often influenced by many factors. PA cannot be easily excluded when negative ARR. Case presentation We report the case of a 45-year-old Chinese man with resistant hypertension. Three years ago, he underwent a comprehensive screening for secondary hypertension, including the ARR, and the result was negative. After that, the patient's blood pressure was still poorly controlled with four kinds of antihypertensive drugs, the target organ damage of hypertension progressed, and hypokalaemia was difficult to correct. When the patient was hospitalized again for comprehensive examination, we found that aldosterone levels had significantly increased, although the ARR was negative. An inhibitory test with saline was further carried out, and the results suggested that aldosterone was not inhibited; therefore, PA was diagnosed. We performed a unilateral adenoma resection for this patient, and spironolactone was continued to control blood pressure. After the operation, blood pressure is well controlled, and hypokalaemia is corrected. Conclusion When the ARR is negative, PA cannot be easily excluded. Comprehensive analysis and diagnosis should be based on the medication and clinical conditions of patients.

scholarly journals Patients With Primary Aldosteronism Respond to Unilateral Adrenalectomy With Long-Term Reduction in Salt Intake

2019 ◽  
Vol 105 (3) ◽  
pp. e484-e493
Author(s):  
Christian Adolf ◽  
Daniel A Heinrich ◽  
Finn Holler ◽  
Benjamin Lechner ◽  
Nina Nirschl ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Sodium Excretion ◽  
Salt Intake ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Care Hospital ◽  
Unilateral Adrenalectomy ◽  
The Impact

Abstract Context High dietary salt intake is known to aggravate arterial hypertension. This effect could be of particular relevance in the setting of primary aldosteronism (PA), which is associated with cardiovascular damage independent of blood pressure levels. The aim of this study was to determine the impact of therapy on salt intake in PA patients. Patients and Methods A total of 148 consecutive PA patients (66 with unilateral and 82 with bilateral PA) from the database of the German Conn’s Registry were included. Salt intake was quantified by 24-hour urinary sodium excretion before and after initiation of PA treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results At baseline, unilateral PA patients had a significantly higher urinary sodium excretion than patients with bilateral disease (205 vs 178 mmol/d, P = 0.047). Higher urinary sodium excretion correlated with an increased cardiovascular risk profile including proteinuria, impaired lipid, and glucose metabolism and was associated with higher daily doses of antihypertensive drugs to achieve blood pressure control. In unilateral disease, urinary sodium excretion dropped spontaneously to 176 mmol/d (P = 0.012) 1 year after unilateral adrenalectomy and remained low at 3 years of follow-up (174 mmol/d). In contrast, treatment with mineralocorticoid receptor antagonists (MRA) in bilateral PA patients was not associated with a significant change in urinary sodium excretion at follow-up (179 mmol/d vs 183 mmol/d). Conclusion PA patients consuming a high-salt diet, estimated based on urinary sodium excretion, respond to adrenalectomy with a significant reduction of salt intake, in contrast to MRA treatment.

scholarly journals Genetics in endocrinology: Genetics of mineralocorticoid excess: an update for clinicians

2013 ◽  
Vol 169 (1) ◽  
pp. R15-R25 ◽  
Author(s):  
Maria-Christina Zennaro ◽  
Amanda Jane Rickard ◽  
Sheerazed Boulkroun
Keyword(s):  
Blood Pressure ◽  
Current Knowledge ◽  
Organ Damage ◽  
Secondary Hypertension ◽  
Genetic Determinants ◽  
Increased Risk ◽  
Aldosterone Production ◽  
Aldosterone Producing Adenoma ◽  
Inherited Mutations ◽  
Type 3

Aldosterone plays a major role in the regulation of sodium and potassium homeostasis and blood pressure. More recently, aldosterone has emerged as a key hormone mediating end organ damage. In extreme cases, dysregulated aldosterone production leads to primary aldosteronism (PA), the most common form of secondary hypertension. However, even within the physiological range, high levels of aldosterone are associated with an increased risk of developing hypertension over time. PA represents the most common and curable form of hypertension, with a prevalence that increases with the severity of hypertension. Although genetic causes underlying glucocorticoid-remediable aldosteronism, one of the three Mendelian forms of PA, were established some time ago, somatic and inherited mutations in the potassium channel GIRK4 have only recently been implicated in the formation of aldosterone-producing adenoma (APA) and in familial hyperaldosteronism type 3. Moreover, recent findings have shown somatic mutations in two additional genes, involved in maintaining intracellular ionic homeostasis and cell membrane potential, in a subset of APAs.This review summarizes our current knowledge on the genetic determinants that contribute to variations in plasma aldosterone and renin levels in the general population and the genetics of familial and sporadic PA. Various animal models that have significantly improved our understanding of the pathophysiology of excess aldosterone production are also discussed. Finally, we outline the cardiovascular, renal, and metabolic consequences of mineralocorticoid excess beyond blood pressure regulation.

scholarly journals Impact of immunohistochemistry on the diagnosis and management of primary aldosteronism: An important tool for improved patient follow-up

2019 ◽  
Vol 109 (2) ◽  
pp. 133-142 ◽  
Author(s):  
C. Volpe ◽  
B. Hamberger ◽  
J. Zedenius ◽  
C. C. Juhlin
Keyword(s):  
Primary Aldosteronism ◽  
Significant Risk ◽  
Final Diagnosis ◽  
Secondary Hypertension ◽  
Histopathological Diagnosis ◽  
Unilateral Adrenalectomy ◽  
Aldosterone Producing Adenoma ◽  
Histopathological Workup ◽  
Cure Rates

Background and Aims: Primary aldosteronism is a common cause of secondary hypertension. Primary aldosteronism is caused by an aldosterone-producing adenoma or bilateral hyperplasia that in some cases is asymmetrical with one adrenal dominating aldosterone secretion. Most patients with aldosterone-producing adenoma are biochemically cured by unilateral adrenalectomy, but patients with bilateral hyperplasia have a significant risk of residual or recurrent disease. Here, immunohistochemistry of CYP11B1 and B2 was used to investigate whether these markers could aid in the diagnostic workup of primary aldosteronism patients. Materials and Methods: A total of 39 patients with primary aldosteronism who underwent unilateral adrenalectomy for a presumed adenoma during 2013–2016 were included. Immunohistochemistry using monoclonal antibodies identifying the enzymes CYP11B1 and B2 was part of routine histopathological workup in 6 cases; in 33 cases, it was applied retrospectively. The hyperplasia diagnosis was suggested when there was no dominating nodule but immunoreactivity for CYP11B2 was seen in several nodules, which were also seen on routine sections. To distinguish between adenoma and hyperplasia, a ratio between the largest and second largest CYP11B2-positive nodules was calculated. Results: In all, 22 patients had an aldosterone-producing adenoma, while 13 patients were judged to have hyperplasia. In four cases, a final diagnosis could not be established, thus these were judged equivocal. Among the 33 cases investigated retrospectively, the primary histopathological diagnosis was altered from hyperplasia to aldosterone-producing adenoma in 9 cases (27%) after immunohistochemistry, and the immunohistochemically rectified adenoma group displayed improved clinical cure rates compared to the routine H&E-diagnosed cohort. Moreover, the B2 ratio was significantly higher in adenoma than in hyperplasia and equivocal cases. Conclusion: Immunohistochemistry detecting CYP11B1 and B2 expression is of great help in establishing a final histopathological diagnosis in patients with primary aldosteronism. This procedure should be part of the histopathological routine in all operated primary aldosteronism patients.

Abstract 12591: Impact of Aldosterone Producing Adenoma on Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takeshi Matsumoto ◽  
Yukihito Higashi ◽  
Nozomu Oda ◽  
Akimichi Iwamoto ◽  
Yumiko Iwamoto ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Primary Aldosteronism ◽  
Vascular Function ◽  
Cardiovascular Events ◽  
Plasma Renin ◽  
Secondary Hypertension ◽  
Plasma Aldosterone Concentration ◽  
Significant Difference ◽  
Aldosterone Producing Adenoma ◽  
Rock Activity

Background: Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs) activity. Primary aldosteronism (PA) is a most common cause of secondary hypertension. Recent studies have shown that risk of cardiovascular events is higher in patients with PA than in patients with essential hypertension (EH). However, there is little information on the relationship between subtype of PA and the grade of atherosclerosis. The purpose of this study was to evaluate the vascular function and ROCK activity in patients with PA. Methods: Vascular function, including flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation, and ROCK activity in peripheral leukocytes were evaluated in 21 patients with aldosterone producing adenoma (APA) group (50.7±14.3 years, 9 males), 23 patients with idiopathic hyperaldosteronism (IHA) group (55.8±9.9 years, 12 males), and 33 age-, gender-, and blood pressure-matched EH group (54.9 ± 10.7 years, 18 males). Results: FMD was significantly lower in the APA group than in the IHA group and EH group (3.2±2.0% vs. 4.6±2.3% and 4.4±2.2%, P<0.05, respectively), whereas there was no significant difference in FMD between the IHA group and EH group. There was no significant difference in the response of nitroglycerine in three groups. ROCK activity was significantly higher in the APA group than in the IHA group and EH group (1.29±0.57 vs. 1.00±0.46 and 0.81±0.36, P<0.05 and P<0.001, respectively), whereas there was no significant difference in ROCK activity between the IHA group and EH group. FMD correlated with age (r=-0.31, P<0.01), brachial arterial diameter (r=-0.44, P<0.01), plasma aldosterone concentration (PAC) (r=-0.35, P<0.01) and plasma renin activity ratio (ARR) (r=-0.34, P<0.01). ROCK activity correlated with age (r=-0.24, P=0.04), PAC (r=0.33, P<0.01) and ARR (r=0.46, P<0.01). Conclusions: APA was associated with both endothelial dysfunction and increased ROCK activity compared with those in IHA and EH. These findings suggest that APA may have a higher risk of future cardiovascular events.

Primary Aldosteronism: Novel Insights

2020 ◽  
Vol 16 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Konstantinos Stavropoulos ◽  
Konstantinos Imprialos ◽  
Vasilios Papademetriou ◽  
Charles Faselis ◽  
Kostas Tsioufis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Molecular Basis ◽  
Diagnostic Procedure ◽  
Secondary Hypertension ◽  
Future Research ◽  
The Novel ◽  
Future Perspectives ◽  
Common Causes ◽  
Existing Data

Background: Primary aldosteronism is one of the most common causes of secondary hypertension. Patients with this endocrine syndrome are at increased cardiovascular risk, higher than hypertensive individuals with equal blood pressure levels. Objectives: The study aimed to thoroughly present and critically discuss the novel insights into the field of primary aldosteronism, focusing on the clinically meaningful aspects. Method: We meticulously evaluated existing data in the field of primary aldosteronism in order to summarize future perspectives in this narrative review. Results: Novel data suggests that a subclinical form of primary aldosteronism might exist. Interesting findings might simplify the diagnostic procedure of the disease, especially for the localization of primary aldosteronism. The most promising progress has been noted in the field of the molecular basis of the disease, suggesting new potential therapeutic targets. Conclusion: Several significant aspects are at early stages of evaluation. Future research is essential to investigate these well-promising perspectives.

scholarly journals KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism

2019 ◽  
Vol 104 (10) ◽  
pp. 4695-4702 ◽  
Author(s):  
Leticia A P Vilela ◽  
Marcela Rassi-Cruz ◽  
Augusto G Guimaraes ◽  
Caio C S Moises ◽  
Thais C Freitas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Somatic Mutation ◽  
Primary Aldosteronism ◽  
Antihypertensive Drugs ◽  
Independent Predictor ◽  
Blood Pressure Response ◽  
Antihypertensive Medications ◽  
Unilateral Adrenalectomy ◽  
Molecular Features ◽  
Endocrine Hypertension

AbstractContextPrimary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear.ObjectiveTo determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.MethodsWe retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.ResultsKCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004).ConclusionThe presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

Study on clinical and endocrine characteristics of dexamethasone-suppressible hyperaldosteronism compared with those in primary aldosteronism owing to aldosterone-producing adenoma

1989 ◽  
Vol 121 (3) ◽  
pp. 334-344 ◽  
Author(s):  
Noriyoshi Yamakita ◽  
Keigo Yasuda ◽  
Nobuyasu Noritake ◽  
Leilani B. Mercado-Asis ◽  
Hiroshi Murase ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Blood Pressure Response ◽  
Laboratory Data ◽  
Japanese Patients ◽  
Pressure Response ◽  
Plasma Aldosterone ◽  
Vascular Damage ◽  
Aldosterone Producing Adenoma

Abstract. The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasonesuppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.

scholarly journals Disordered CYP11B2 Expression in Primary Aldosteronism

2017 ◽  
Vol 49 (12) ◽  
pp. 957-962 ◽  
Author(s):  
Celso Gomez-Sanchez ◽  
Maniselvan Kuppusamy ◽  
Martin Reincke ◽  
Tracy Williams
Keyword(s):  
Primary Aldosteronism ◽  
Secondary Hypertension ◽  
Zona Glomerulosa ◽  
Common Type ◽  
Older Individuals ◽  
Cell Clusters ◽  
Cellular Expression ◽  
Normal Individuals ◽  
Aldosterone Producing Adenoma

AbstractPrimary aldosteronism is the most common type of secondary hypertension affecting 6–10% of patients with primary hypertension. PA is mainly caused by unilateral hyperaldosteronism due to an aldosterone-producing adenoma, unilateral hyperplasia with or without micronodules or bilateral zona glomerulosa hyperplasias with or without macro or micronodules. The development of antibodies against the terminal enzyme of aldosterone biosynthesis (CYP11B2) has permitted the further characterization of normal adrenals and resected adrenals from patients with primary aldosteronism. Normal adrenals exhibit two different patterns of cellular expression of CYP11B2: young individuals display a relatively uniform expression of the enzyme throughout the zona glomerulosa while the adrenals of older individuals have dispersed CYP11B2-expressing cells but have more groups of cells called aldosterone-producing cell clusters (APCC). APAs exhibit different patterns of CYP11B2 staining that vary from uniform to homogeneous. There are also a proportion of cells within the APA that co-express different enzymes that are not normally co-expressed in normal individuals. Approximately 30% of patients with unilateral hyperaldosteronism do not have an APA, but either have an increased number of CYP11B2 expressing micronodules or hyperplasia of the zona glomerulosa. In summary, the studies reported in this review are shedding new light on the pathophysiology of primary aldosteronism. The wide variation in histopathological features of the adenomas and concurrent presence of APCCs raises the possibility that most cases of unilateral production of aldosterone actually might represent bilateral asymmetric hyperplasia with nodules frequently due to the development of somatic aldosterone-driving mutations.

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