A Reappraisal of the Diagnostic Criteria for Primary Aldosteronism

1982 ◽  
Vol 63 (s8) ◽  
pp. 97s-100s ◽  
Author(s):  
E. L. Bravo ◽  
R. C. Tarazi ◽  
F. M. Fouad ◽  
S. C. Textor
Keyword(s):  
Primary Aldosteronism ◽  
Excretion Rate ◽  
False Negative ◽  
False Negative Rate ◽  
Plasma Renin ◽  
Dietary Sodium ◽  
Screening Tests ◽  
Plasma Aldosterone Concentration ◽  
Salt Loading ◽  
Aldosterone Producing Adenoma

1. Results in 80 patients with primary aldosteronism (70 with tumour, 10 with hyperplasia) who underwent stimulation and suppression tests were analysed to assess the usefulness of several screening techniques. 2. On normal dietary sodium, normokalaemia was found in 27.5% of patients; 12.5% remained so despite 3 days of salt loading. Suppressed plasma renin activity (PRA: less than 1.43 pmol/l after stimulated conditions) gave a false-negative rate of 36%. Thus sole reliance on either hypokalaemia (serum potassium less than 3.5 mmol/l) or suppressed PRA as primary screening tests would have overlooked about a third of the patients in this series. 3. The single best diagnostic test for primary aldosteronism was the measurement of aldosterone excretion rate after 3 days of salt loading. 4. An anomalous postural fall in plasma aldosterone concentration when present, coupled with adrenal venous sampling, provided the best indicators of the presence of an aldosterone-producing adenoma.

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.

scholarly journals Effects of Ramipril on the Aldosterone/Renin Ratio and the Aldosterone/Angiotensin II Ratio in Patients With Primary Aldosteronism

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 488-496 ◽  
Author(s):  
Zeng Guo ◽  
Marko Poglitsch ◽  
Diane Cowley ◽  
Oliver Domenig ◽  
Brett C. McWhinney ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Ace Inhibitors ◽  
Primary Aldosteronism ◽  
Characteristic Curve ◽  
False Negative ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Plasma Aldosterone Concentration

The aldosterone/renin ratio (ARR) is currently considered the most reliable approach for case detection of primary aldosteronism (PA). ACE (Angiotensin-converting enzyme) inhibitors are known to raise renin and lower aldosterone levels, thereby causing false-negative ARR results. Because ACE inhibitors lower angiotensin II levels, we hypothesized that the aldosterone/equilibrium angiotensin II (eqAngII) ratio (AA2R) would remain elevated in PA. Receiver operating characteristic curve analysis involving 60 patients with PA and 40 patients without PA revealed that the AA2R was not inferior to the ARR in screening for PA. When using liquid chromatography-tandem mass spectrometry to measure plasma aldosterone concentration, the predicted optimal AA2R cutoff for PA screening was 8.3 (pmol/L)/(pmol/L). We then compared the diagnostic performance of the AA2R with the ARR among 25 patients with PA administered ramipril (5 mg/day) for 2 weeks. Compared with basally, plasma levels of equilibrium angiotensin I (eqAngI) and direct renin concentration increased significantly ( P <0.01 or P <0.05) after ramipril treatment, whereas eqAngII and ACE activity (eqAngII/eqAngI) decreased significantly ( P <0.01). The changes of plasma renin activity and plasma aldosterone concentration in the current study were not significant. On day 14, 4 patients displayed false-negative results using ARR_direct renin concentration (plasma aldosterone concentration/direct renin concentration), 3 of whom also showed false-negative ARR_plasma renin activity (plasma aldosterone concentration/plasma renin activity). On day 15, 2 patients still demonstrated false-negative ARR_plasma renin activity, one of whom also showed a false-negative ARR_direct renin concentration. No false-negative AA2R results were observed on either day 14 or 15. In conclusion, compared with ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in detecting PA among subjects receiving ACE inhibitors.

scholarly journals Minireview: Primary Aldosteronism—Changing Concepts in Diagnosis and Treatment

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2208-2213 ◽  
Author(s):  
William F. Young
Keyword(s):  
Plasma Renin Activity ◽  
Primary Aldosteronism ◽  
Activity Ratio ◽  
Cardiovascular Effects ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Receptor Blockade ◽  
Plasma Aldosterone Concentration ◽  
Aldosterone Producing Adenoma

Abstract Primary aldosteronism affects 5–13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of primary aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with primary aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperaldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.

scholarly journals Stable Serum Potassium After Intracerebral Hemorrhage Is Predictive of Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A298-A299
Author(s):  
Makoto Arai ◽  
Katsunari Kiko ◽  
Shigeru Oya
Keyword(s):  
Intracerebral Hemorrhage ◽  
Serum Potassium ◽  
Primary Aldosteronism ◽  
Functional Independence Measure ◽  
Plasma Renin ◽  
Functional Independence ◽  
Screening Tests ◽  
Negative Group ◽  
Plasma Aldosterone Concentration ◽  
Positive Group

Abstract Background: Primary aldosteronism (PA) is a well-known risk factor for cardiovascular complications including intracerebral hemorrhage (ICH). Still, there seem to be many PA patients who have been missing the opportunities for the diagnosis of PA even after stroke. PA screening tests in all stroke patients are, however, inefficient. Here we focused on ICH, where hypertension has a great contribution, and searched for the indications of performing PA screening tests in ICH patients. Methods: 1) Out of 181 ICH patients admitted to our hospital between June 2016 and February 2017, 126 patients of hypertensive ICH were enrolled in this study. Plasma aldosterone concentration (PAC), plasma renin activity (PRA) and other hormones were measured in the morning two days after admission. 2) 1,242 hypertensive ICH patients admitted to our hospital after January 2013 were retrospectively reviewed Results: 1) After excluding those who had been taking medications which could intervene with PAC or PRA on admission, nine patients were positive for PA screening (PAC/PRA ratio &gt;200 and PAC &gt;120 pg/mL) and 46 were negative. Age (68.6 vs 67.1 y), sex (male 66.7 vs 67.3 %) and blood pressure (172/97 vs 177/100 mmHg) were similar between these two groups. Serum potassium was slightly lower in positive group on admission (3.6 vs 3.9 mmol/L; P=0.108), and the difference became more evident two days later (3.7 vs 4.0 mmol/L; P=0.042). There were no differences in other hormones including cortisol and catecholamine on day 2. PA positive patients had more severe motor or cognitive impairments (Functional independence measure 58 vs 95; P=0.015). 2) After collecting 25 clinical parameters in 1,242 hypertensive ICH patients, dimension reduction procedure using t-SNE certainly divided these patients into clusters compatible with PA screening tests. Only 4% of PA positive group showed serum potassium lower than 3.5 mmol/L on admission (sensitivity 97%), and the increase in serum potassium during the first 2 days were milder in PA positive group (P=0.001). Discussion: This is the largest study ever that investigated the clinical features of PA in ICH patients. We uncovered that transitional changes of serum potassium after the onset of ICH were efficient markers to decide who should go on to PA screening tests. ICH increases sympathetic activity and subsequent renin secretion, resulting in low serum potassium even in PA negative group. But about two days later, when its activity peaked out, serum potassium in PA negative group restores to their original states while that in PA positive group are stable due to constitutive secretion of aldosterone. Since ICH patients with PA are at higher risk for recurrent hemorrhage and other complications, diagnosis of PA is important even after the occurrence of ICH. PA screening should not be awaited just because they have developed ICH.

scholarly journals Screening for Primary Aldosteronism in Essential Hypertension: Diagnostic Accuracy of the Ratio of Plasma Aldosterone Concentration to Plasma Renin Activity

2005 ◽  
Vol 51 (2) ◽  
pp. 386-394 ◽  
Author(s):  
Gary L Schwartz ◽  
Stephen T Turner
Keyword(s):  
Drug Therapy ◽  
Diagnostic Accuracy ◽  
Antihypertensive Drug ◽  
Primary Aldosteronism ◽  
Plasma Renin ◽  
Dietary Sodium ◽  
Antihypertensive Drug Therapy ◽  
Sodium Balance ◽  
Likelihood Ratios ◽  
Plasma Aldosterone Concentration

Abstract Background: The ratio of plasma aldosterone concentration to plasma renin activity (PRA) is considered the screening test of choice for primary aldosteronism. Uncertainty exists, however, regarding its diagnostic accuracy and the effects of antihypertensive drugs and dietary sodium balance on test characteristics. Methods: We measured PRA and aldosterone in 118 white adults [71 men and 47 women; mean (SD) age, 51 (7) years] with previously diagnosed essential hypertension. Measurements were made while individuals were on antihypertensive drug therapy, after a 2-week drug-free period, after 4 days of dietary sodium loading, and after acute furosemide diuresis. We measured 24-h urine aldosterone excretion and PRA on the 4th day of dietary sodium loading to establish the diagnosis of primary aldosteronism. ROC curves were constructed for ratios measured under each clinical condition, and likelihood ratios were determined for individuals on or off antihypertensive drug therapy. Results: Fifteen patients [13%; 95% confidence interval (CI), 7–20%] met the reference standard for primary aldosteronism. The mean (SD) areas under the ROC curves did not differ significantly across conditions of measurement [range, 0.80 (0.10) to 0.85 (0.04); P = 0.72]. When measured on and off antihypertensive drug therapy, the 95% CIs for the optimum cutpoint for the ratio overlapped. Point estimates of sensitivity on and off therapy were 73% (95% CI, 50–96%) and 87% (70–100%), respectively, and specificities were 74% (65–83%) and 75% (66–84%). Under either condition, increased ratios were associated with 2.4- to 13-fold increases of posttest odds above pretest odds. Conclusions: The aldosterone:PRA ratio provides only fair diagnostic accuracy in screening for primary aldosteronism, but concomitant antihypertensive drug therapy or acute variation in dietary sodium balance does not adversely affect test accuracy. Reporting of likelihood ratios associated with ranges of values of the aldosterone:PRA ratio, rather than use of a single “optimum” cutpoint, may enhance the usefulness of the test.

scholarly journals Primary aldosteronism in Klinefelter’s syndrome: two cases

2019 ◽  
Vol 2019 ◽  
Author(s):  
Yasufumi Seki ◽  
Satoshi Morimoto ◽  
Naohiro Yoshida ◽  
Kanako Bokuda ◽  
Nobukazu Sasaki ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Primary Aldosteronism ◽  
Luteinizing Hormone Receptor ◽  
List Type ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Plasma Aldosterone Concentration ◽  
Lh Receptor ◽  
Serum Lh ◽  
Aldosterone Producing Adenoma

Summary Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered. Learning points: The pathogenesis of primary aldosteronism is still unclear. Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma. Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

Abstract P612: The AA2-Ratio: Towards Improved Screening for Primary Aldosteronism

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Marko Poglitsch ◽  
Ashraf H Ahmed ◽  
Andrea Stoller ◽  
Dunja van Oyen ◽  
Oliver Domenig ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Ace Inhibitor ◽  
False Negative ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Serum Samples ◽  
Drug Interference ◽  
Salt Loading ◽  
Hypertensive Patients

Background: Primary aldosteronism (PA) is a widely under-diagnosed, potentially curable and specifically treatable cause of hypertension. PA screening involves measuring the aldosterone-to-renin-ratio (ARR), but false negative results can occur in the setting of medications, which block the renin-angiotensin system (RAS). Withdrawing RAS blockers from patients with resistant hypertension is not without cardiovascular risk. A novel diagnostic approach, the aldosterone-to-angiotensin-II-ratio (AA2-Ratio), has the potential for less drug interference and improved reliability in PA screening and confirmation of diagnosis. Methods: Serum samples from 80 patients undergoing PA confirmation testing were analyzed. Sampling was performed in a recumbent (7 a.m.) and in an upright (10 a.m.) position before and after 4 days of oral administration of fludrocortisone and salt loading. The concentrations of renin, aldosterone and equilibrium Angiotensin-II were determined and ARR and AA2-Ratios were calculated. The interference of ACE-inhibition with the AA2-Ratio was investigated in healthy volunteers receiving 10mg enalapril daily for 8 days. Results: Renin concentration was undetectable in more than 40% of samples, while equilibrium Angiotensin-II was measurable in 98% of all 320 samples analyzed. Angiotensin-II levels were significantly higher in upright collected samples compared to samples collected in a recumbent position. Comparison of the ARR with the AA2-Ratio revealed a significantly larger diagnostic window for the AA2-Ratio. While the ARR was significantly suppressed by ACE-inhibitor treatment, the AA2-Ratio remained unaffected by ACE-inhibition. Conclusion: The AA2-Ratio may be superior to the ARR in PA screening among hypertensive patients. Equilibrium Angiotensin-II levels show expected responses to posture and appear to outperform renin concentration as a marker for RAS activation in terms of sensitivity, giving a measurable readout even in clinical states characterized by markedly suppressed RAS activity. The stability of the AA2-Ratio in the presence of ACE-inhibition points to a potential use of the AA2-Ratio PA screening in hypertensive patients without ACE-inhibitor discontinuation.

Adrenal Vein Catecholamine Levels and Ratios: Reference Intervals Derived from Patients with Primary Aldosteronism

2017 ◽  
Vol 49 (06) ◽  
pp. 418-423 ◽  
Author(s):  
Candy Sze ◽  
Samuel O’Toole ◽  
Roger Tirador ◽  
Scott Akker ◽  
Matthew Matson ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Imaging Techniques ◽  
False Negative ◽  
False Negative Rate ◽  
Reference Intervals ◽  
Adrenal Venous Sampling ◽  
Venous Sampling ◽  
Few Data ◽  
Histological Confirmation ◽  
The Right

AbstractPhaeochromocytoma localisation is generally reliably achieved with modern imaging techniques, particularly in sporadic cases. On occasion, however, there can be diagnostic doubt due to the presence of bilateral adrenal abnormalities, particularly in patients with mutations in genes predisposing them to the development of multiple phaeochromocytomas. In such cases, surgical intervention is ideally limited to large or functional lesions due to the long-term consequences associated with hypoadrenalism. Adrenal venous sampling (AVS) for catecholamines has been used in this situation to guide surgery, although there are few data available to support diagnostic thresholds. Retrospective analyses of AVS results from 2 centres were carried out. A total of 172 patients (88 men, 84 women) underwent AVS under cosyntropin stimulation for the diagnosis of established primary aldosteronism (PA) with measurement of adrenal and peripheral venous cortisol, aldosterone and catecholamines. Six patients (3 men, 3 women) with phaeochromocytoma underwent AVS for diagnostic purposes with subsequent histological confirmation. Reference intervals for the adrenal venous norepinephrine to epinephrine ratio were created from the PA group. Using the 97.5th centile (1.21 on the left, 1.04 on the right), the false negative rate in the phaeochromocytoma group was 0%. In conclusion, this study describes the largest dataset of adrenal venous catecholamine measurements and provides reference intervals in patients without phaeochromocytoma. This strengthens the certainty with which conclusions related to adrenal venous sampling for catecholamines can be drawn, acknowledging the procedure is not part of the routine diagnostic workup and is an adjunct for use only in difficult clinical cases.

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