Normal Plasma Aldosterone Concentration Research Articles

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with a Normal Plasma Aldosterone Concentration

PurposeTo determine the utility of adrenal vein sampling (AVS) and outcomes after adrenalectomy in patients with normal plasma aldosterone concentration (PAC) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 106 patients with ARR greater than 20 and PAC between 5 and 15 ng/dL (normal PAC group) who underwent AVS from 2005 to 2021. These patients were compared with a cohort of 106 patients with ARR >20 and PAC >15 ng/dL (high PAC group) who underwent AVS during the same period. Data regarding baseline clinical characteristics, lateralization indices from AVS, and outcomes after adrenalectomy were analyzed. ResultsAVS was technically successful in 210 patients (210/212, 99%). A smaller proportion of patients in the normal PAC group showed a lateralization index of >4 compared with those in the high PAC group (44% vs 64%, P <.01). A similar proportion of patients in the normal PAC group experienced improved or cured hypertension after adrenalectomy compared with that in the high PAC group (94% vs 88%, P =.31). Hypokalemia was cured in all patients in the normal PAC group after adrenalectomy compared with 98% of patients in the high PAC group (100% vs 98%, P = 1). ConclusionsAlthough lateralization is less frequent for patients with normal PAC, patients who do lateralize show similar blood pressure response and correction of hypokalemia after adrenalectomy, regardless of initial plasma aldosterone levels. Therefore, patients with PAC <15 ng/dL should still be considered for AVS provided the ARR is elevated.

Hypocortisolism in a dog caused by bilateral pheochromocytoma

AbstractWe present a 12‐year‐old French bulldog with muscle weakness, epigastric pain, weight loss, high systolic blood pressure and cardiac arrhythmias. Physical and laboratory examination revealed no abnormalities. On a computed tomography scan, severely enlarged adrenals were found, and endocrine and biochemical evaluations excluded hypercortisolism and hyperaldosteronism. Urinary metanephrine and normetanephrine/creatinine ratios were elevated, compatible with a diagnosis of pheochromocytoma. Symptomatic treatment with phenoxybenzamine was started and resulted in normalisation of a systolic blood pressure and reduction of arrhythmias. However, the onset of anorexia, vomiting and clinical deterioration prompted exploration of the adrenocortical reserve through an adrenocorticotropic hormone stimulation test, which confirmed glucocorticoid deficiency. Mineralocorticoid deficiency was ruled out by normal plasma aldosterone concentration and renin activity. Finally, an elevated endogenous plasma adrenocorticotropic hormone concentration defined the primary origin of the hypocortisolism. Clinical resolution occurred with prednisolone supplementation. This is the first report of hypocortisolism in a dog caused by a bilateral pheochromocytoma.

Abstract No. 391 Adrenal vein sampling results and surgical outcomes in patients with a normal plasma aldosterone concentration

Abstract No. 391 Adrenal vein sampling results and surgical outcomes in patients with a normal plasma aldosterone concentration

Malignant hypertension and hyperreninemia: primary or secondary hypertension? A case report

Malignant hypertension is a rare condition characterized by severe hypertension and multi-organ ischemic damage. Marked activation of the renin-angiotensin system is observed in many patients, but its persistence over time is not known. We report a case of a 42-year-old woman who presented with severe hypertension and multi-organ damage. Initial evaluation showed an elevated value of direct renin concentration with normal plasma aldosterone concentration and a nodular lesion in the left adrenal gland. The differential diagnosis between the primary and secondary form of hypertension had to be questioned. Consequently, the patient was followed up for 20 months. Repeated checks showed a significant increase in renin levels with a normal aldosterone concentration and regression of organ damage. After 20 months, renin values returned within normal range. Hyperreninemia persisting over a long period of time has not been fully explained. Long-term follow-up allowed us to attribute malignant hypertension to de novo essential hypertension.

PLASMA RENIN ACTIVITY AND ALDOSTERONE IN RENAL TRANSPLANT PATIENTS

(Background) It has become evident in recent year that aldosterone has a pathogenic role in hypertension, heart failure and renal disease. Elevation of aldosterone occurs in a certain fraction of hemodialysis patients, and the adverse effects of hyperaldosteronism could pose a problem after kidney transplantation. Long-term effects of aldosterone level in renal transplant recipients remain unknown. (Materials and methods) All recipients underwent transplantation between 1996 and 2018 in Niigata university hospital were included in the study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were retrospectively analyzed in 210 recipients before and after kidney transplantation. (Results) Sixty percent of recipients had higher PRA than normal upper limit before and after transplantation. The use of angiotensin receptor blocker (ARB) or angiotensin-converting-enzyme inhibitor (ACEI) was significantly more frequent in the patients with hyperreninemia than those without one after transplantation. Sixty percent of recipients had higher PAC than normal upper limit before transplantation and it spontaneously decreased to normal level after transplantation in most of them. There was no significant correlation between PAC and blood pressure, recipient age, and renal graft function after transplantation. We divided the patients into two groups, with and without post-transplant hyperaldosteronemia. The patients with post-transplant hyperaldosteronemia (n=29) had higher diastolic blood pressure and less use of renin-angiotensin-aldosterone system (RAAS) inhibitors than those with normal PAC level. (Conclusions) The use of RAAS inhibitors should be considered in post-transplant hyperaldosteronemia patients to control blood pressure and to save their long-term renal graft and heart function.

Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism

Previous studies showed higher risk of cardiovascular and cerebrovascular (CCV) events in primary aldosteronism compared with essential hypertension, but the patients of these studies were limited to primary aldosteronism patients with high plasma aldosterone concentration (PAC). The introduction of the aldosterone-renin ratio as the screening test for primary aldosteronism led to the recognition of primary aldosteronism patients with normal PAC (nPA). However, there is no information on the risk of primary aldosteronism including nPA. In this retrospectively and cross-sectional study, the clinical features and CCV event risk of primary aldosteronism at diagnosis including nPA were investigated and compared with essential hypertension. The study included 292 consecutive primary aldosteronism patients and 498 essential hypertension outpatients. All primary aldosteronism patients were diagnosed by autonomous aldosterone secretion using confirmatory tests, and then divided into nPA (n = 130) and primary aldosteronism patients with high PAC (hPA: n = 162) using a PAC cutoff level of less than 443 pmol/l (16 ng/dl), representing the normal upper limit of PAC. nPA patients were significantly older at diagnosis of primary aldosteronism and at onset of hypertension compared with hPA patients. They had milder hypokalemia and easier-to-control blood pressure. The results suggested that nPA could be considered a mild type of primary aldosteronism but not an early-stage hPA. Moreover, the risk of all CCV events in nPA was significantly lower than that in hPA (odds ratio 0.42, 95% confidence interval 0.18-0.90, P < 0.05) and not significantly higher than that in essential hypertension (odds ratio 0.95, 95% confidence interval 0.43-1.94, P = 0.899). This study suggests that aggressive diagnostic workout for nPA is less effective to prevent CCV events.

Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin–angiotensin–aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P < 0.05) at an early stage of the disease.In this study, we showed a high prevalence of PA in ADPKD patients, associated to higher LVMI, HOMA-IR, Hcy, lower FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with ADPKD is recommended.

Synergic effects of renin and aldosterone on right ventricular function in hypertension: a tissue Doppler study.

Right ventricular dysfunction (RVD) is associated with poor cardiovascular outcome. The renin-angiotensin-aldosterone system is involved in alterations of the left ventricular geometry and function. Detrimental effects of the renin-angiotensin-aldosterone system on the right ventricular function are being postulated, but data supporting this assumption are still lacking. The aim of the study was to assess the impact of hyperreninemia, hyperaldosteronism or their combination on right ventricular function in hypertensive individuals. Plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) were measured in 116 hypertensive patients, divided as follows: normal PRA and PAC (n = 38); high PRA and normal PAC (hypereninemia) (n = 26); normal PRA and high PAC (hyperaldosternism) (n = 27); high PRA and PAC (HRA) (n = 25). Echocardiographic evaluation of the left and right ventricles (RV), including tissue Doppler imaging, was performed. RVD was identified by tissue Doppler Imaging-derived Myocardial Performance Index, calculated with a multisegmental approach. Indices of the right ventricular structure and function, as well as the prevalence of RVD, were higher in hyperreninemia and hyperaldosternism groups as compared with the normal group, and a further increase was observed in the HRA patients. Regression models showed a similar risk of RVD in the hyperreninemia and hyperaldosternism patients, regardless of systemic and pulmonary pressure, as well as left ventricular dysfunction. Notably, patients with both hyperreninemia and hyperaldosternism exhibited the strongest association with RVD as compared with patients with only hyperreninemia or hyperaldosternism. Isolated hyperreninemia or hyperaldosternism determines a similar impairment of the right ventricular function, whereas their combination is further detrimental. Renin and aldosterone may represent early biomarkers of right ventricular dysfunction in hypertension.

Abstract P211: Normo-aldosteronemic Aldosterone-producing Adenoma: Immunochemical Characterization and Diagnostic Implications

Background: Primary Aldosteronism (PA), the most common form of endocrine hypertension, is usually identified by a high aldosterone-renin ratio (ARR) alongside elevated plasma aldosterone concentration (PAC) values. Normo-aldosteronemic PA is also being diagnosed when only the high ARR was driven by low renin because PAC was normal. However, whether this entity truly exists remains contentious since most such cases did not undergo surgical confirmation and even when adrenalectomy was performed no demonstration of an aldosterone-producing adenoma (APA) could be obtained at immunohistochemistry. Case Description: In 2003 a young lady presented with severe hypertension, low plasma renin activity (PRA), but consistently normal PAC values. She undertook a magnetic resonance that revealed a small adenoma on the right side, but adrenal vein sampling (AVS) showed left lateralization of aldosterone secretion. Therefore, she underwent left laparoscopic adrenal surgery, which determined complete normalization of blood pressure and PRA long term follow up (12 years). In 2014 the development of novel monoclonal antibodies for the human aldosterone synthase CYP11B2 and 11β-hydroxylase CYP11B1, allowed us to immunochemically characterize the resected adrenal gland. Double immunostaining for CYP11B2 and CYP11B1 showed a small CYP11B2-positive adenoma, thus unequivocally proving the presence of an APA. Conclusions: This case provides compelling evidence for the existence of normo-aldosteronemic APA and suggests that many cases that we dismiss as “low renin-essential hypertension” might instead have an undetected surgically curable APA.

Plasma Aldosterone and Heart Failure in the General Community

and 687pg/ml, respectively. BNP decreased in both groups at discharge (60% for MSASV vs. 40% for standard care). However, after 3 days, BNP in the standard care group had increased to a median of 920pg/ml, while BNP in the MV-ASV group demonstrated a continued and marked decrease to a median of 353pg/ml. Compared to admission, the 3 day Likert Breathing scores demonstrated an average 52% increase in the MV-ASV group, versus a 24% increase in the standard care group. Conclusion: The use of MV-ASV in patients with ADHF resulted in a rapid early improvement in dyspnea as well as a marked drop in BNP levels, suggesting mitigations of pulmonary edema and neurohormonal activity.

Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome

Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular disorder resulting from inactivating mutations in the asolateral chloride channel (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely rare, especially in middle age. A 45-year-old Chinese female patient was referred for evaluation of chronic severe hypokalemia despite regular K+ supplementation (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting, diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal. Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8 mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22 mmol/mol), high plasma renin activity, but normal plasma aldosterone concentration. Abdominal sonography revealed neither renal stones nor nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC), revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited from her parents; her SLC12A3 was normal. These two mutations were not identified in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after the addition of spironolactone. Inherited cBS may present with hypokalemic paralysis and should be considered in adult patients with hypokalemia and metabolic alkalosis.

Childhood hypertension due to a rare cause

A 3 year 6 month old child, presented with complaints of fever, loose stools and vomiting. The child had no signs of dehydration and was noted to be hypertensive with blood pressure of 120/76mm Hg (95th centile for age, sex and height: 104/65 mm Hg). All the peripheral pulses were equal and well felt. There was no radiofemoral delay, no abdominal bruit. The child had been reared as a female, had normal female external genitalia and no palpable gonads. Urine evaluation, Renalfunction test and USG abdomen were normal. Child had Metabolic alkalosis with hypokalemia. Elevated Urine chloridesuggested a saline non responsive metabolic alkalosis. Markedly elevated 24 hour urine potassium and TTKG (Transtubular potassium gradient) was suggestive of tubular potassium wasting in the presence of hypokalemia.Plasma Renin Activity (PRA) was low, with low normal plasma aldosterone concentration (PAC). Serum Cortisol (8AM) was low with elevated ACTH. Basal and post ACTH 17 hydroxy progesterone was low with elevated total progesterone levels. The karyotype was 46XX.This clinical and biochemical picture was suggestive of 17 alpha hydroxylase (CYP 17) deficiency. The patient was started on hydrocortisone therapy. With this, the blood pressure got controlled, the patient gained height, weight, the pigmentation decreased, serum potassium normalized. Thus, the diagnosis of, 17 alpha hydroxylase deficiency,a rare form of Congenital Adrenal Hyperplasia, should be considered in any child with systemic hypertension, especially in the presence of concomitant hypokalemia with metabolic alkalosis. More commonly, it presents in the peripubertal period, during evaluation of delayed puberty. The presentation as early childhood hypertension is rare. Plan to confirm the diagnosis by genetic analysis. Table showing various investigations

NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features.

Objective. We retrospectively analyzed all primary aldosteronism (PA) patients undergoing NP-59 SPECT/CT imaging with regard to their clinicolaboratory and imaging features, investigation, and outcomes. Material and Methods. 11 PA patients who presented to our hospital for NP-59 SPECT/CT imaging between April 2007 and March 2012 and managed here were analyzed. Results. Among 11 PA patients, eight (73%) had stage 1 hypertension, three (27%) stage 2 hypertension, four (36%) normal plasma aldosterone concentration, nine (82%) nonsuppressed plasma renin activity (PRA), six (55%) normal aldosterone-renin-ratio (ARR), eight (73%) serum potassium ≧3 mEq/L, seven (64%) subclinical presentation, seven (64%) negative confirmatory testing, and four (36%) inconclusive results on CT scan and seven (64%) on planar NP-59 scan. All 11 (100%) patients had positive results on NP-59 SPECT/CT scan. Two (18%) met typical triad and nine (82%) atypical triad. Among nine atypical PA patients, three (33%) had clinical presentation, six (67%) subclinical presentation, six (67%) negative confirmatory testing, and four (44%) inconclusive results on CT scan and six (67%) on planar NP-59 scan. All patients had improved outcomes. Significant differences between typical and atypical PA existed in PRA and ARR. Conclusions. NP-59 SPECT/CT may provide diagnostic potential in stage 1 hypertensive and atypical PA.

Adrenal corticosteroid effects in the central nervous system on long-term control of blood pressure

Adrenal corticosteroid effects in the central nervous system on long-term control of blood pressure

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

A Case with Primary Aldosteronism Due to Unilateral Multiple Adrenocortical Micronodules

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.

Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism.

An increased plasma aldosterone concentration (PAC) with decreased plasma renin activity (PRA) is the abnormal endocrine finding in primary aldosteronism (PA). However, it remains unknown whether this profile is universal when blood samples are obtained in a random manner. We retrospectively evaluated the renin/aldosterone profile in 71 patients with PA due to unilateral adrenal adenoma. Blood samples were obtained randomly at an out-patient clinic and under standardized conditions during hospitalization before surgery. The frequency of PAC above 15 ng/dl, PRA below 0.5 ng angiotensin I/ml x h, and a PAC/PRA ratio greater than 35 was determined. These three variables showed a large intra- and interpatient variation. At least one measurement of PAC, PRA, and PAC/PRA ratio was in the normal range in 39%, 48%, and 31% of patients, respectively. Only 37% of patients always had the characteristic profile associated with PA. The mean values of PAC at the out-patient clinic were slightly, but significantly, lower than those in the hospital. These results clearly demonstrated that the renin/aldosterone profile in PA is not always abnormal due in part to conditions for blood sampling. We conclude that a single normal PAC, PRA, or PAC/PRA ratio does not excluded the diagnosis of PA in a hypertensive patient, but repeated measurements yields one or more abnormal parameters in the vast majority of patients. The PAC/PRA ratio is recommended to use as a screening, but other testing is required to arrive at the correct diagnosis.

Tissue-Specific Regulation of Growth Factors and Clusterin by Angiotensin II

Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-β 1 (TGF-β 1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-β 1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF-β 1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-β 1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.

Renin-angiotensin-aldosterone system in cirrhosis.

According to traditional concepts, ascites formation and portal hypertension in cirrhosis lead to a deficit in the 'effective' extracellular fluid (ECF) and blood volumes respectively. The renin-angiotensin-aldosterone (RAA) system is thus stimulated and the kidneys retain fluid as a homeostatic mechanism to restore the ECF and blood volumes. Recent studies, however, show that approximately two-thirds of patients with ascites do not have a stimulated RAA system and in those without clinical evidence of fluid retention the RAA system is actually suppressed. These findings are incompatible with the concepts of reduced effective ECF and blood volumes. Despite the fact that most patients retaining sodim and accumulating ascites have a normal plasma aldosterone concentration, other evidence strongly suggests a dominant role for aldosterone in the regulation of renal sodium excretion. There might therefore be an increased renal tubular sensitivity to aldosterone in cirrhosis. For the one-third of patients with ascites who do have a stimulated RAA system this may well be a response to reduced effective ECF and/or blood volumes in accord with traditional concepts.