Confirmatory Testing in Primary Aldosteronism

Nanba, Kazutaka; Tamanaha, Tamiko; Nakao, Kazuwa; Kawashima, Sachiko–Tsukamoto; Usui, Takeshi; Tagami, Tetsuya; Okuno, Hiroshi G.; Shimatsu, Akira; Suzuki, Tomoko; Naruse, Mitsuhide

doi:10.1210/jc.2011-2504

Cited by 71 publications

(62 citation statements)

References 27 publications

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“…20,28 Of these testing, lack of 24-hour urine aldosterone data after oral salt-loading test and FDST as the most reliable confirmatory testings 17 is a significant limitation of the present study in the specificity of the diagnosis of PA and non-PA. We have demonstrated that negative results in both of CCT and SIT were seen only in 1 (1.7%) of the 57 hypertensive patients with positive case detection. 29 Mulatero et al 21 also reported that SIT is a reliable alternative to the FDST for confirming the diagnosis of PA. In addition, we used a PAC cutoff of 50 pg/mL for the SIT, a more permissive value for PA and stricter one for non-PA than used in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

et al. 2016

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Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154–69 920) in the higher side and 12 953 (range, 1866–36 190) pg/mL in the lower side ( P <0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4–66.0] versus 17.3 [4.0–59.0] pg/mL per μg/dL; P <0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA.

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Section: Discussionmentioning

confidence: 99%

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

et al. 2016

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“…In addition, at our institution, we have long used the same definition of an abnormal ARR along with high-probability features (eg, ARR >2200 pmol L −1 ng −1 mL −1 h −1 and hypokalemia) to identify highly probable PA, even without further conventional confirmatory testing with few (<3%) false-positive results, 14 as is consistent with other reports. 21,22 Second, we also did not systematically use any aldosterone cutoff as part of our screening criteria. As such, it is possible that some of our cases may have had lower than typical aldosterone levels.…”

Section: Discussionmentioning

confidence: 99%

“…This is in keeping with previous reports that a marked elevation in the ARR with highprobability features is highly specific for PA with few false-positive results. 14,21,22 Second, a probable diagnosis was defined by an ARR >2200 pmol L −1 ng −1 mL −1 h −1 without consideration of potassium. Finally, a possible diagnosis was defined by an ARR >550 pmol L .…”

Section: Case Definitionsmentioning

confidence: 99%

Novel Approach to Establishing an Aldosterone: Renin Ratio Cutoff for Primary Aldosteronism

et al. 2017

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P rimary aldosteronism (PA) is a common form of remediable hypertension. The aldosterone:renin ratio (ARR) is the recommended screening test for PA in individuals with hypertension with or without hypokalemia. [1][2][3] Elevations in the ratio are predominantly dependent on renin measurements, 2 thus any alteration to the renin assay will have an impact on the resulting ARR. 4 Plasma renin activity (PRA) has traditionally been used to calculate the ARR; however, measurement of direct renin concentration (DRC) has become increasingly popular because the assay procedure is less labor and time intensive. Although numerous conversion factors have been proposed in an effort to generate clinically meaningful and stable cutoffs between assays, 1 it remains uncertain whether an interchangeable relationship exists, especially as PRA and DRC are biologically distinct entities. Head-to-head comparisons are often performed by simultaneously measuring PRA and DRC, looking for correlations to establish stable conversion factors. Such studies are generally small thus limiting their general applicability. [5][6][7][8][9][10][11] Moreover, the Endocrine Society has advised that the correlation between PRA and DRC is poor at lower renin levels, the domain of greatest importance for PA screening. 1 Indeed, differences in analytical method can result in as much as a 2-fold variation in ARR cutoffs and classification error.12 On a population level, this may result in significant downstream consequences with tremendous clinical and public health implications.Addressing this, we developed a novel yet easily generalizable approach to determining ARR cutoffs using population-based data without relying on direct assay comparisons or conversion factors. The specific aim of our study was to produce a new DRC-based ARR threshold consistent with an established PRA-based ARR cutoff, thus providing diagnostic congruity with established thresholds used in routine practice. Our approach is based on 2 inter-related assumptions: first, in a defined healthcare system with a relatively static population pool, screening is performed in similar types of patients; and second, of those who are screened, the prevalence of PA has remained stable over time.Abstract-Direct renin concentration is replacing plasma renin activity in many laboratories for the investigation of primary aldosteronism, which may have a significant impact on the resulting aldosterone:renin ratios. We sought to develop a population-based approach to establishing an aldosterone:renin ratio cutoff when transitioning between assays. A population-based study was performed in Calgary, Alberta, Canada of 4301 individuals who received testing from January 2012 to November 2015. In 2014, direct renin concentration replaced plasma renin activity in routine testing. We described the prevalence of primary aldosteronism in our population before the change and, using the assumption of disease prevalence stability, determined the corresponding ratio cutoffs after the introduction of the new assay....

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“…Blood samples for PRA or DRC, aldosterone, and potassium are drawn at time zero and after 2 h. PRA < 2 ng/mL/h (or DRC < 24 mU/L) confirms the PA diagnosis (26). Although patients with essential hypertension can present low renin levels, plasma renin activity (PRA) increases above 2 ng/mL/h after furosemide injection.…”

Section: Screening and Case Confirmationmentioning

confidence: 99%

Diagnosis and management of primary aldosteronism

Vilela

Almeida

2017

Arch. Endocrinol. Metab.

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Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age-and sexmatched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia. Aldosterone-producing adenomas (APAs) account for around 40% and idiopathic hyperaldosteronism for around 60% of PA cases. The aldosterone-to-renin ratio is the most sensitive screening test for PA. There are several confirmatory tests and the current literature does not identify a "gold standard" confirmatory test for PA. In our institution, we recommend starting case confirmation with the furosemide test. After case confirmation, all patients with PA should undergo adrenal CT as the initial study in subtype testing to exclude adrenocortical carcinoma. Bilateral adrenal vein sampling (AVS) is the gold standard method to define the PA subtype, but it is not indicated in all cases. An experienced radiologist must perform AVS. Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with APAs, and bilateral hyperplasia should be treated with mineralocorticoid antagonist (spironolactone or eplerenone). Cardiovascular morbidity caused by aldosterone excess can be decreased by either unilateral adrenalectomy or mineralocorticoid antagonist. In this review, we address the most relevant issues regarding PA screening, case confirmation, subtype classification, and treatment. Arch Endocrinol Metab.2017;61(3):305-12.

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Confirmatory Testing in Primary Aldosteronism

Abstract: Most patients with positive case detection also had positive results on the CCT and FUT, especially when ARR was at least 1000 or PAC was at least 250 pg/ml under renin suppresion. Confirmatory testing for PA may not be needed in all patients with positive case detection.

Cited by 71 publications

References 27 publications

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

Novel Approach to Establishing an Aldosterone: Renin Ratio Cutoff for Primary Aldosteronism

Diagnosis and management of primary aldosteronism

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