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Context: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear., Objective: To compare the clinical outcomes in patients treated for primary aldosteronism over time., Methods: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models., Results: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months., Conclusion: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized., Methods: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension., Results: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P <0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP., Conclusions: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension., Competing Interests: Disclosures Dr Vaidya reports consulting fees from Mineralys, Corcept, and HRA Pharma, outside of the submitted work. Dr Brown reports consulting fees from Bayer and AstraZeneca, outside of the submitted work. Dr Sood reports speaker fees from AstraZeneca, Otsuka, Bayer, and GlaxoSmithKline, outside of the submitted work.

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with primary aldosteronism (PA) have increased morbidity and mortality compared to those with essential hypertension. Accurate detection of lateralized PA is important so that affected patients can receive potentially curative adrenalectomy. However, around 40% of patients with lateralized PA have "normal" adrenal glands on computed tomography (CT). Additional independent review of imaging has been shown to improve diagnostic accuracy in many areas of imaging. Therefore, the authors sought to establish if multi-reader re-assessment of previously reported normal CT scans would result in increased detection of surgically remediable disease. The authors found that re-assessment of CT imaging by one, two, or three additional radiologists (or a combination thereof) slightly increased the detection of lateralized disease, but these differences were not statistically significant (p > .05). Readers had low inter-observer agreement (kappa = 0.17). If detection of a discrete nodule on CT was made a prerequisite for adrenal vein sampling (AVS), a second read by another reviewer would still result in an excess of missed cases (84.2%, 36.8%, and 65.8%, respectively, for each of the three independent reviewers). Therefore, a "normal" CT does not preclude the possibility of lateralized PA. Adrenal vein sampling should still be strongly considered wherever available and whenever surgery is considered for treatment of PA, irrespective of CT findings., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice., Methods: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling., Results: The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care., Conclusions: The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated., Objective: To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors., Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension., Main Outcomes and Measures: We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics., Results: Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program., Conclusions and Relevance: In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.

Purpose of Review: Primary aldosteronism, characterized by renin-independent aldosterone secretion from one or both adrenal glands, is the most common and modifiable form of secondary hypertension. The prevalence of primary aldosteronism is increasingly recognized to be much higher than previously thought with many cases still undetected., Recent Findings: Prior prevalence studies on primary aldosteronism have reported a wide range of estimates due to heterogeneity of both disease definitions and study populations such that it is difficult to claim a single point estimate. More recent evidence demonstrates that primary aldosteronism, as defined by conventional biochemical diagnostic criteria, is highly prevalent within populations where it is not typically considered such as mild-to-moderate hypertension, prehypertension, and even normotension. Yet, our current screening approach fails to capture many cases. Furthermore, there is mounting evidence that renin-independent aldosteronism exists as a continuum of disease that extends below the current biochemical diagnostic thresholds used to define primary aldosteronsim and has clinically relevant treatment and outcome implications for a much broader patient population. Indeed, much of what we current label as 'essential hypertension' is, in fact, renin-independent aldosterone-mediated hypertension., Summary: Primary aldosteronism and milder forms of renin-independent aldosteronism are highly prevalent, yet vastly under-recognized, in the general population., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: Ally Prebtani has received consultant and speaker fees from Servier and is the Chair, Endocrine Section, Hypertension Canada, Clinical Practice Guidelines. Ernesto Schiffrin has received grants from the Canadian Institutes of Health Research and Servier France. He has received lecture fees from Servier Canada, and consultant and lecture fees from Novartis US. No other competing interests were declared.

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. During the initial portion of the study (using plasma renin activity), 4.9% of those screened were classified as highly probable cases, whereas 10.4% were considered probable and 28.9% possible using locally validated cutoffs. Aldosterone:renin ratio cutoffs were then determined for the direct renin concentration assay. A highly probable case of primary aldosteronism corresponded to a cutoff of >100 pmol L -1 mIU -1 L -1 with hypokalemia. A probable case corresponded to a cutoff of >100 and a possible case to >35 pmol L -1 mIU -1 L -1 In contrast, cutoffs derived using a conversion factor resulted in significantly higher cutoffs and the potential for missed cases. In conclusion, using large population data, historically consistent aldosterone:renin ratio cutoffs can be established when transitioning between assays. Population-derived cutoffs may be more appropriate for clinical use and less likely to result in false-negative classification than those obtained from conventional direct method comparisons., (© 2017 American Heart Association, Inc.)

Unilateral primary aldosteronism (PA) is often treated with adrenalectomy, but hypertension resolution rates are variable. A valid estimate of the postoperative normotension rate is necessary to inform the utility of PA testing and treatment. The authors searched MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials. Prospective adult cohort studies with surgically treated PA that reported resolution of hypertension without the aid of medications were included. Among 2620 abstracts identified by the search, 25 studies in the systematic review with data on 1685 patients were investigated. The pooled proportion of normotension following adrenalectomy was 52% (95% confidence interval, 0.44-0.60). Meta-regression demonstrated a significant negative association between length of follow-up and proportion of normotension, with normotension dropping by 6.7% per year of follow-up (coefficient -0.006; 95% confidence interval, -0.01 to 0.002). Overall, approximately half of the patients experienced hypertension resolution, although this outcome may not be durable in all patients., (©2016 Wiley Periodicals, Inc.)

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P =0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P =0.022) and adrenalectomy (72% versus 54%; P =0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220. [ABSTRACT FROM AUTHOR]

BACKGROUND Targeted treatment of primary aldosteronism (PA) is informed by adrenal vein sampling (AVS), which remains limited to specialized centers. Clinical prediction models have been developed to help select patients who would most likely benefit from AVS. Our aim was to assess the performance of these models for PA subtyping. METHODS This external validation study evaluated consecutive patients referred for PA who underwent AVS at a tertiary care referral center in Alberta, Canada during 2006–2018. In alignment with the original study designs and intended uses of the clinical prediction models, the primary outcome was the presence of lateralization on AVS. Model discrimination was evaluated using the C -statistic. Model calibration was assessed by comparing the observed vs. predicted probability of lateralization in the external validation cohort. RESULTS The validation cohort included 342 PA patients who underwent AVS (mean age, 52.1 years [SD, 11.5]; 201 [58.8%] male; 186 [54.4%] with lateralization). Six published models were assessed. All models demonstrated low-to-moderate discrimination in the validation set (C -statistics; range, 0.60–0.72), representing a marked decrease compared with the derivation sets (range, 0.80–0.87). Comparison of observed and predicted probabilities of unilateral PA revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.35–1.67), signifying systematic underprediction of lateralizing disease. Calibration slopes were consistently <1 (range, 0.35–0.87), indicating poor performance at the extremes of risk. CONCLUSIONS Overall, clinical prediction models did not accurately predict AVS lateralization in this large cohort. These models cannot be reliably used to inform the decision to pursue AVS for most patients. [ABSTRACT FROM AUTHOR]

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220. [ABSTRACT FROM AUTHOR]

Context: The reproducibility of adrenal vein sampling (AVS) is unknown.Objective: This work aimed to determine reproducibility of biochemical results and diagnostic lateralization in patients undergoing repeat AVS.Methods: A retrospective chart review was conducted of single-center, single-operator AVS procedures at a tertiary care center. Included were patients with confirmed primary aldosteronism (PA) undergoing repeat AVS because of concerns about technical success or discordant diagnostic results. Simultaneous AVS was performed by an experienced operator using a consistent protocol of precosyntropin and postcosyntropin infusion. Among successfully catheterized adrenal veins (selectivity index ≥ 2), the correlation of the adrenalaldosterone/cortisol (A/C) ratio was measured between the first and second AVS. The secondary outcome measure was diagnostic agreement on repeat AVS lateralization (lateralization index ≥ 3).Results: There were 46 sets of AVS from 23 patients at a median of 3 months apart. There was moderate correlation in A/C ratios in the adrenal veins and inferior vena cava (Spearman r = 0.49-0.59, P < .05) pre cosyntropin. Post cosyntropin, the correlation was better (Spearman r = 0.67-0.76, P < .05). In technically successful AVS, there was moderate correlation between the repeated lateralization indices (Spearman r = 0.53, P < .05). In 15 patients in whom repeat AVS was performed because of apparent lateralization discordance with computed tomography imaging, the final diagnosis was the same in the second AVS procedure. Initial failed AVS was successful 75% of the time on repeat attempt.Conclusion: Repeat AVS was feasible and usually successful when an initial attempt failed. There was modest correlation between individual repeat adrenal A/C ratios and lateralization indices when AVS was performed twice. The final lateralization diagnosis was identical in all cases. This demonstrates that AVS is a reliable and reproducible localizing test in PA. [ABSTRACT FROM AUTHOR]

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220. [ABSTRACT FROM AUTHOR]

Endocrine hypertension, particularly primary aldosteronism (PA), was previously considered to account for less than 1% of all hypertension and was suspected only when patients presented with spontaneous hypokalemia. However, the last 20 years of PA research has now clearly shown that PA is not a rarity, but rather, may account for up to 13% of unselected hypertensive individuals and between 10% and 20% of those with resistant hypertension. Most of these patients do not have spontaneous hypokalemia. The population prevalence of PA likely far exceeds actual detection rates in routine clinical care. As PA represents one of the most common, potentially reversible causes of hypertension, and is associated with significant cardiovascular complications over the long term, it is clear that a pragmatic strategy for targeted case detection in primary care is needed. [ABSTRACT FROM AUTHOR]

The article discusses the accumulating epidemiologic evidence on hypertension and primary aldosteronism that is resistant to treatment. Topics discussed include assessment of patients with very severe hypertension not able to tolerate drug adjustment for aldosterone-to-renin ratio (ARR) measures by a hypertension specialist, consideration of empiric trial of eplerenone or spironolactone for blood pressure control and repeating of tests if high clinical suspicion of primary aldosteronism.

Background: Pheochromocytoma is a rare cause of acute cardiovascular disease; however, any severe illness may have high catecholamines, simulating pheochromocytoma. We determined the spectrum of urine metanephrines from inpatient and outpatient collections without pheochromocytoma, compared with confirmed pheochromocytoma patients.Methods: Retrospective analysis using centralized laboratory data serving all outpatients and hospitals in southern Alberta. The analysis comprised 24-hour urine normetanephrine and metanephrine (UNM-UMN) results collected from hospital inpatients, community outpatients, and patients from a comprehensive provincial pheochromocytoma registry.Results: There were 974 unique inpatients (including 132 from intensive care), 6802 outpatients, and 58 pheochromocytoma patients. Among outpatient, general ward, and intensive care unit (ICU) patients, 18.7%, 34.4%, and 67.4% of results, respectively, were supranormal. Although pheochromocytoma patients had higher median UNM-UMN vs inpatients, there was substantial overlap. Receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.64-0.91 to detect true pheochromocytoma (P < .0001), with progressively poorer discrimination among hospitalized and ICU-dependent patients. A 24-hour urine normetanephrine >6.95 nmol/d had 98% specificity for pheochromocytoma when inpatient general ward samples were included, but only 46% sensitivity and 13% positive predictive value for pheochromocytoma. Considering ICU collections, 98% specificity required results more than fivefold above the upper reference limit and still had poor positive predictive value. A model combining both UNM and UMN results as a cross-product marginally improved the ROC AUC, but improved sensitivity in outpatients and ward patients but not ICU patients.Conclusion: There is a high degree of overlap in UNM-UMN between hospitalized patients and pheochromocytoma; high test specificity is not achieved in this population unless >3-5 times the upper reference limit. [ABSTRACT FROM AUTHOR]