Screening For Primary Aldosteronism Research Articles

Potential effects of age on screening for primary aldosteronism.

Aldosterone/renin ratio (ARR) is currently regarded as the most reliable and available screening test for primary aldosteronism (PA), however, the falling accuracy of ARR with increasing age has posed crucial challenge for PA screening among older-aged population. To clarify potential effects of age on screening for PA, 216 subjects with PA and 657 subjects with non-PA were recruited and subdivided into four age groups (⩽39, 40-49, 50-59 and ⩾60 years) and their biochemical parameters were compared. As expected, plasma renin activity (PRA) lowered more than plasma aldosterone concentration (PAC) and led to gradually elevated ARR with increasing age in the non-PA group (P<0.001), whereas this phenomenon was unconspicuous in the PA group. The best cut-off values of ARR for PA screening were elevated in subjects ⩾50 years, whereas the area under the receiver operating characteristic curves (AUCs), sensitivity, specificity and Youden's index (YI) of ARR were declined with increasing age, especially in patients ⩾60 years (AUC=0.863, sensitivity=95.2%, specificity=69.0%, YI=0.643). The AUCs of PAC increased with increasing age and even slightly surpassed that of ARR in patients ⩾60 years (AUCPAC=0.884). Our data suggest that the criteria of ARR for PA screening in patients ⩾50 years may need setting higher; the falling accuracy of ARR with increasing age, especially in patients ⩾60 years, could be improved by taking into account the absolute value of the PAC when applicable by the center.

Screening for Primary Aldosteronism: Whom and How?

Screening for Primary Aldosteronism: Whom and How?

Lower aldosterone-renin ratio is a risk factor for total and cancer death in Japanese individuals: the Takahata study.

A higher plasma aldosterone-renin ratio (ARR) is an established marker for screening for primary aldosteronism (PA). The association between higher ARR and mortality in a general population has not been fully explored. We here examined whether higher ARR is a risk factor for total and cause-specific mortality in a Japanese population. A population-based, longitudinal study of 1,310 Japanese individuals (age: 63·9±9·8years) enrolled in the Takahata study between 2004 and 2006 and followed for up to 8years. The incidence and causes of death were monitored annually until 10 January 2012 (median follow-up: 2691days). During the follow-up period, 64 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total and cancer mortality in subjects with lower ARR (log-rank P<0·001). Cox's proportional hazard model analyses with adjustment for age and gender showed that lower ARR was associated with increased total and cancer mortality in subjects with low (≦72) vs high (>72) ARR (hazard ratios and 95% confidential intervals: 2·56, 1·44-4·56 and 2·78, 1·16-6·65, respectively). Lower ARR was a significant and independent risk factor for increased total and cancer mortality in this Japanese population. Subjects with higher ARR were not-at-risk for total death in general. These findings increase the necessity for identifying people with PA from those with higher ARR. People with higher ARR without PA may be at very low risk for total and cancer death.

Abstract 431: A Novel Score System for Primary Aldosteronism Screening, PUK2 score: Combination of Urine pH and Serum Uric Acid and K+ Levels

Background: Hypokalemia is not a sensitive marker of primary aldosteronism (PA) , and method for screening PA by routine clinical parameters has not yet been established. Objective: We examined whether serum uric acid (UA) or urine pH alone, or their combination with serum K+ level is usable for PA screening . Design and Setting: Cross-sectional analyses were retrospectively performed on consecutive patients who visited a single general hospital from April 2012 to September 2013. Participants: Entry criteria were age &lt;75 years old, hypertension and presence of data on serum aldosterone (ng/dL) and renin activity (ng/mL/hr). Exclusion criteria were use of aldosterone blockers, ACE inhibitors, angiotensin receptor antagonists, diuretics, beta-adrenergic blockers, steroids or UA-lowering drugs and diagnosis of secondary hypertensions other than PA. Main Outcome Measures: Diagnosis of PA was made in accordance with the guideline of Japanese Society of Hypertension: patients with aldosterone-to-renin activity ratio (ARR) &gt; 20 and one or more positive results in captopril challenge test, furosemide-upright test, saline infusion test and/or ACTH stimulation test. Results: We enrolled 103 patients (PA = 29, essential hypertension [eHT] = 74). PA has lower serum K+ (3.5±0.32 vs 3.8±0.23 mEq/L, p&lt;0.001, mean ± S.D.), higher urine pH (6.6±0.83 vs 6.1±0.62, p&lt;0.001) and lower UA (5.6±1.6 vs 6.5±1.2 mg/dL, p=0.004) compared with those in eHT. Urine pH≧ 7.0 and UA &lt; 6.0 mg/dL were selected as optimum cutoffs for diagnosis of PA by ROC curve analysis. Multivariable logistic regression analysis indicated that high urine pH, low UA and hypokalemia (K &lt; 3.5 mEq/L) were independently associated with PA. Using the cutoff values, we developed a score system, PUK2 score, which is derived from the sum of point values of PA predictor; 1 point was assigned to low UA and to high urine pH and 2 points were assigned to hypokalemia. The prevalence of PA in the patients with PUK2 score of 0, 1, 2 and 3~ was 5.0%, 31%, 37%, and 83%,respectively. Furthermore, the likelihood ratio in patients with PUK2 score of 0 was 0.13 (95%CI: 0.034-0.52). Conclusions: PUK2 score is easy to use and useful for screening PA in hypertensive patients.

The influence of aging on the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is common in young or middle-aged hypertensive patients, but PA among the elderly has recently become more common. As salt sensitivity increases with age, plasma renin activity (PRA) tends to decrease, whereas the aldosterone-to-renin ratio (ARR) tends to increase in the elderly. The aim of this study was to clarify the influence of aging on the diagnosis of PA. We retrospectively evaluated 155 consecutively admitted patients who were not taking antihypertensive medications or calcium channel blockers and α blockers that underwent PRA and plasma aldosterone concentration (PAC) measurements. The study subjects included 13 PA and 69 essential hypertensive (EHT) patients aged over 65 years, and 32 PA and 41 EHT patients under aged 65 years. Our study clarified the influence of aging through screening and confirmatory tests for the diagnosis of PA. Our results showed the ARR cutoff value for a screening test to be 556 (area under the curve: AUC=0.906), its sensitivity and specificity to be 84.6% and 89.9%, respectively, and the likelihood ratio to be 8.34 in the elderly, whereas the ARR cutoff value was 272 in the non-elderly. In the saline infusion test, the mean PAC was 86.6 ± 41.8 pg ml(-1) in the elderly and 158.1 ± 116.5 pg ml(-1) in the non-elderly (P = 0.04). There was no influence from age in both the captopril challenge test and the furosemide upright test. Aging may influence PA screening and saline infusion tests; thus, we should consider the influence of aging in the diagnosis of elderly subjects with PA.

Application of SUSPPUP ratio in patients with primary aldosteronism

Objective To assess the effectiveness of the quotient of serum sodium to urinary sodium divided by (serum potassium) 2 to urinary potassium (SUSPPUP) in screening for primary aldosteronism (PA).Methods Among 952 patients with hypertension who had renin activity,aldosterone measurements and concomitant serum and urinary biochemistry data,204 patients were diagnosed as cases of PA and 261 as cases of essential hypertension.Diagnosis of PA was made in accordance with established laboratory criteria including renin activity and aldosterone,plasma aldosterone concentration/plasma renin activity (ARR),and saline loading test.The SUSPPUP ratio with the ARR were compared in two groups.Results The area under the curve of SUSPPUP and ARR was 0.797 and 0.796 respectively according to receiver operating characteristic curve,optimal cutoff of SUSPPUP was 1.0,the sensitivity and specificity of SUSPPUP was 98.9％ and 81％ respectively.Conclusions The SUSPPUP ratio is an inexpensive and rapid tool to assess the extent of mineralocorticoid excess,therefore,SUSPPUP ratio can be applied to screen PA in hypertensive patients. Key words: Primary aldosteronism; Hypertension; Urinary potassium; Serum potassium

Marinobufagenin in essential hypertension and primary aldosteronism: a cardiotonic steroid with clinical and diagnostic implications

Background: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA).Methods: Plasma MBG concentrations (mean: 0.51 ± 0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women).Results: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68 ± 0.12 versus 0.35 ± 0.24 nmol/l; p < 0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at > 0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at > 3.32 ng/dl/µU/ml.Conclusions: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA.

Combination of LC–MS/MS aldosterone and automated direct renin in screening for primary aldosteronism

BackgroundAldosterone to renin ratio (ARR) is used in screening for primary aldosteronism (PA). However, there are only few studies on the influence of assay methods on ARR and its cut-off limits. MethodsPlasma direct renin immunoreactivity by chemiluminescence immunoassay (DR) was compared to renin activity assay (PRA), and a specific liquid chromatography–mass spectrometric method (LC–MS/MS) to radioimmunoassay (RIA) for plasma aldosterone. There were 75 samples for renin assays, and 42 samples of 39 patients for both renin and aldosterone assays. PA screening was considered positive if ARR by the aldosterone RIA:PRA was ≥800pmol/L:μg/L/h or by LC–MS/MS:DR≥44pmol/L:ng/L. ResultsThe correlation between the DR and PRA methods (n=75, r2=0.845) and between LC–MS/MS and RIA (n=42, r2=0.973) was high in general, but low between the renin methods (n=49, r2=0.435) at low PRA values. When ARR was used in screening for PA, there were three divergent cases (positive only by alternative methods), but when applied in combination with criteria for elevated aldosterone, the methods showed good agreement, resulting in eight positive and 31 negative screening results. ConclusionsThe automated DR assay combined with LC–MS/MS method for aldosterone provides a rapid, reliable, and specific method for screening of PA.

Case Detection Testing for Primary Aldosteronism in Male Patients with Hypertension and Snoring

Objectives: Coexistence of primary aldosteronism and obstructive sleep apnea in hypertension is evidenced. However, aldosterone and renin activity is varying with apnea/hypopnea index changes in subjects with resistant hypertension. Thus, the aim is to investigate the optional cutoff value for aldosterone/renin activity to screen primary aldosteronism in patients with different status of apnea/hypopnea index. Methods: 271 hypertensive male snores were evaluated via polysomnography and divided into two groups, group with apnea/hypopnea index >15 events/h and with apnea/hypopnea index 15 ng/dL performed saline infusion test, after which aldosterone concentration>5 ng/dL was a sign of primary aldosteronism. Receiver operating characteristic curve was applied to explore appropriate cutoff value for aldosterone/renin activity. Results: 39 (14.4%) of the 271 were diagnosed with primary aldosteronism including 15 with apnea/hypopnea index 15 events/h. Area under receiver operating characteristic curve was 0.97 (95%CI 0.94-0.99) in the group with apnea/hypopnea index >15 events/h and 0.91 (95%CI 0.87-0.96) in the group with apnea/hypopnea index 15 events/h with sensitivity 100%, specificity 69.7%. Youden index is 0.9 for the group with apnea/hypopnea index 15 events/h. Conclusions: Optional cutoff values of aldosterone/renin activity to screening for primary aldosteronism should be considered in patients with different status of apnea/hypopnea index.

Development and evaluation of an immuno-MALDI (iMALDI) assay for angiotensin I and the diagnosis of secondary hypertension.

Plasma renin activity (PRA) is an essential analytical tool for screening and diagnosis of secondary forms of hypertension. Typically, PRA is measured by competitive radioimmunoassay, but there are significant drawbacks to this technique including non-specificity, long analysis times, narrow calibration range, and the requirement for radionucleotides. In this paper, we report a method for plasma renin activity determination by immuno-MALDI mass spectrometry detection. This method overcomes the issues of non-specificity and long analytical times present with RIA, and does not require the use of radionucleotides. As an initial methodological evaluation, plasma renin activity results obtained by radioimmunoassay, LC/ESI-MS/MS, and immuno-MALDI on 64 samples from an outpatient primary aldosteronism screening program have been compared. A strong correlation was found between immuno-MALDI and radioimmunoassay (R2 = 0.9412, 62/64 within the 95% CI of the Bland-Altman plot), and iMALDI and LC/ESI-MS/MS (R2 = 0.9471, 62/64 within the 95% CI of the Bland-Altman plot). Technical replicates showed a 4.8% CV, while inter- and intra-day replicates showed CVs of 17.3% and 17.2% respectively. We have developed an assay capable of measuring PRA without the use of radionucleotides. This immuno-MALDI approach affords the specificity of MS while avoiding the long analytical run times and technical problems associated with HPLC. With the use of robotic sample preparation to optimize precision, this assay should be adaptable to clinical environments.

Abstract 53: Measurement of Peripheral Blood 18-Oxocortisol as the Diagnostic Method of Primary Aldosteronism and Its Subtypes

Backgrounds: Primary aldosteronism (PA) is diagnosed and treated by the long steps, such as screening, confirmation testing and subtype diagnosis (computed tomography (CT) scan and adrenal venous sampling (AVS)). AVS has been the only reliable subtype classification method between surgically curable unilateral aldosterone producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (BHA). In spite of increased numbers of specialized centers with superior ability of AVS in the world, unfortunately, this test is costly and requires a dedicated and expert radiologist; therefore it is not generally utilizable in most hospitals. It is understandable that easier diagnostic tools to be substitutes for AVS might be hoped by clinicians. Objective: The aim of the study was to determine the role of peripheral plasma levels of 18-oxo-cortisol (p18oxoF) and 18-hydroxycortisol (p18OHF) in differentiate APA from BHA. Patients: The study included 265 PA patients (113 patients with CT-positive macro APA, 31 patients with CT-negative micro APA and 121 patients with BHA) and 79 patients with essential hypertension (EH). Methods: All of 265 PA patients underwent AVS successfully, and any case with APA was surgically proven and pathologically confirmed including immunohistochemical analysis of steroidogenic enzymes. We measured p18oxoF and p18OHF of all PA patients by high sensitive LC ms/ms. Results: APA patients showed significantly higher p18oxoF and p18OHF than those of BHA patients and EH patients. The ROC analysis of p18oxoF in macro APA versus BHA demonstrated clinically useful discrimination with higher sensitivity of 0.83 and higher specificity of 0.99 by cutoff value of 4.7 (ng/dl), compared to the classification by p18OHF. Practically, 86 (76%) of macro APA patients with p18oxoF above 6.1 (ng/dl), which was the maximum level in BHA patients, might have been able to undergo surgery without AVS. Because the maximum p18oxoF in EH patients was 5.6 (ng/dl), the patients with p18oxoF above 6.1 (ng/dl) after screening of PA could also undergo surgery if unilateral adenoma(s) can be found on CT; thus it means omitting confirmation tests. Conclusions: Peripheral blood 18oxoF measurement can be a clinically useful method for the diagnosis of PA and its subtypes.

Aldosterone to renin ratio is associated with 24 hour ambulatory blood pressure in essential hypertensives: the Styrian Hypertension study

Purpose: The aldosterone to renin ratio (ARR) is a screening tool for primary aldosteronism (PA). Accumulating evidence suggests that ARR may be significantly associated with blood pressure (BP) even below the threshold for PA. We therefore aimed to evaluate the relationship between the ARR and 24 hour ambulatory BP monitoring measurements (ABPM). Methods: We recruited essential hypertensive patients derived from the outpatient clinic at the department of internal medicine of the local medical university hospital. ABPM measurements were obtained every 15min during the day (06:00-24:00 o'clock) and every 30 min during the night (00:00–06:00). Plasma aldosterone and plasma renin concentrations were measured by means of a RadioImmunoAssay (RIA). Results: We examined 172 hypertensive patients (age: 59.6±11.3years; 51.2% females) with a mean systolic/diastolic 24-hour ABPM value of 129/77mmHg. In linear regression analyses adjusted for age, sex, 24-hour urinary sodium and body mass index, ARR was significantly associated with night-time systolic (beta coefficient:0.19; p=0.017) and diastolic ABPM (beta coefficient:0.28; p<0.001). In subgroup analyses of patients with ARR below the cut-off for positive PA screening (ARR<3.7 - ng/dl divided by μU/mL) ARR remained significantly associated with diastolic ABPM (beta coefficient:0.26; p=0.001) and by trend with systolic ABPM (beta coefficient:0.15; p=0.056). These associations remained materially unchanged when additionally adjusted for other possible confounders, e.g. antihypertensive medications, HbA1c or NT-proBNP. Conclusions: In patients with essential hypertension and even in those patients not suggestive for PA, we found a strong relationship between ARR and diastolic night-time BP. In view of the strong relationship between diastolic night-time BP and risk of cardiovascular events further studies are needed to evaluate cardio-protective effects of mineralocorticoid blockade in hypertensive patients without PA.

Prevalence of and risk factors for primary aldosteronism among patients with resistant hypertension in China

It is estimated that there are more than 16 million adults with drug-resistant hypertension in China. Nevertheless, the prevalence of and risk factors for primary aldosteronism, a highly curable condition among adults with drug-resistant hypertension, has not been fully investigated. Between January 2010 and October 2011, a multicenter epidemiologic study was conducted among 1656 patients with resistant hypertension in 11 provinces of China. Serum aldosterone and plasma renin activity were measured in every participant and aldosterone-to-renin ratio (ARR) was calculated. Patients with ARR more than 20 underwent an intravenous (i.v.) sodium infusion test, and diagnosis of primary aldosteronism was established by the presence of unsuppressed postinfusion aldosterone (>8 ng/dl). Patients with biochemically proved primary aldosteronism then underwent adrenal computed tomography (CT) scanning and adrenal vein sampling (AVS) for subtype classification. Among the 1656 patients, 494 (29.8%) had ARR greater than 20 and underwent i.v. sodium infusion. Of these 494, 118 were diagnosed as primary aldosteronism, yielding a prevalence of 7.1% (95% confidential interval 5.9-8.3%). Seventy of the 118 patients were categorized into unilateral (39) and bilateral (31) by AVS. Generalized additive regression analysis revealed that among all the factors investigated (age of hypertension onset, BMI, family history of hypertension, cigarette smoking, alcohol consumption, diabetes, serum potassium, hyperlipidemia, and creatinine), only age of hypertension onset and serum potassium were independently associated with the presence of primary aldosteronism. The prevalence of primary aldosteronism among Chinese patients with resistant hypertension is relatively lower than that reported previously for other ethnic populations. The screening for primary aldosteronism should be focused on those with early onset hypertension and/or hypokalemia.

Assay Characteristics Influence the Aldosterone to Renin Ratio as a Screening Tool for Primary Aldosteronism: Results of the German Conn's Registry

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn's Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p<0.0001), renin concentration (p<0.001), and renin activity (p=0.009) for the different assays. The differences between the absolute concentrations measured by the different assays also had significant impact upon the resulting mean ratios. If published cutoff values are applied, the use of different commercial assays to determine the ARR in clinical routine results in major differences in positive screening rates. This heterogeneity affects sensitivity and specificity of screening for PA. Our data emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.

Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

Introduction: Primary aldosteronism (PA) is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR), is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28%) than with adrenal tumors (46,72%). Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

Should all Hypertensive Patients be Screened for Primary Aldosteronism?

Our aim was to determine whether the prevalence of Primary Aldosteronism (PA) in a referral hypertensive population is high enough to warrant routine screening for PA amongst unselected hypertensive’s in general practice. A retrospective clinical audit was conducted on 635 patients referred for specialist hypertension review, over a period of 33 months (March 2009 till December 2011). We found a PA prevalence of (confirmed or probable) in 8/635 referred patients (1.25%) which is lower that the previously reported prevalence. Among the 178 patients who at discharge had met the JNC-7 criteria for resistant hypertension the prevalence was 4.5% (8/178). All the PA cases met the criteria for resistant hypertension, and in addition, all had unprovoked hypokalaemia. We conclude that in our population, routine screening for PA amongst hypertensive individuals in general practice cannot be justified, and that even in a specialist hypertension clinic population investigation should likely be reserved for those with a combination of resistant hypertension and unprovoked hypokalaemia.

Prevalence and clinical characteristics of primary aldosteronism in Japanese patients with type 2 diabetes mellitus and hypertension

The prevalence of primary aldosteronism (PA) is around 3-15% in patients with hypertension. Hypertension is a frequent complication of type 2 diabetes mellitus (DM) because of the close etiological relationship between these two diseases. However, the possibility of PA in patients with DM and hypertension is often overlooked and the prevalence of PA in patients with DM and hypertension in Japan is unknown. We enrolled 124 hospitalized patients with both DM and hypertension. PA was diagnosed according to the modified criteria for Japanese patients. We examined the prevalence of PA and compared clinical characteristics between patients with and without PA. In another analysis of 43 patients with a confirmed diagnosis of PA, we compared the characteristics of patients with and without DM. Overall, 14/124 patients with DM and hypertension (11.3%) were diagnosed with PA. Multivariate logistic regression showed that the duration of DM was significantly shorter in the PA group. Fisher's direct probability test revealed that history of hypertension before the diagnosis of DM was a significant factor in patients with PA. Treatment with an angiotensin II receptor blocker (ARB) did not affect the diagnosis of PA in these patients. Among 43 patients with PA, those with DM were significantly older and the delay to the diagnosis of PA was significantly longer compared with patients without DM. In conclusion, almost 10% of patients with DM and hypertension actually have PA. More extensive screening for PA is recommended in patients with DM and hypertension, regardless of the use of ARBs.

Screening for primary aldosteronism in a primary care unit

Primary aldosteronism (PA) is a common cause of secondary hypertension but the reported prevalence varies. Few studies have been carried out in primary care. We investigated the prevalence of PA by screening with the aldosterone to renin ratio (ARR). Patients with hypertension were recruited from a primary care unit and investigated in a university hospital setting. Of 235 patients asked to participate 77% accepted. Antihypertensive medication apart from amiloride and spironolactone was maintained. The cut-off level for a positive ARR was lower than in clinical practice (> 50 pmol/ng with aldosterone > 350 pmol/l) to adjust for any suppressive effects of medication. A positive ARR was followed by a confirmatory evaluation. The frequency of confirmed PA was 1.6% and including cases with a positive ARR who refused further investigation it would be 3.3% at most. In primary hypertension angiotensin receptor blockers, angiotensin-converting enzyme inhibitors and thiazide diuretics markedly suppressed the ARR by increasing renin levels. The detection rate of PA in our study is in the lower part of the wide range shown in previous studies. Larger population studies are needed to establish the true prevalence in primary care. Future studies may clarify if the present cut-off levels allow detection of very mild PA.

Estimation of the efficacy of the measurement of plasma renin activity and direct renin in diagnostics of primary aldosteronism

The objective of the present study was to estimate the informative value of the measurements of aldosterone level, direct renin, and plasma renin activity as well as the relationships between these characteristics for differential diagnostics of various forms of hypertension and, first and foremost, of primary aldosteronism. We have examined a total of 162 patients. The results of differential tests were used to allocate them to a few groups including 41 patients presenting with primary aldosteronism, 52 ones with incidentalomas, 26 with essential hypertension, and 43 with various endocrine diseases and normal arterial pressure (control groups). The aldosterone levels, direct renin, and plasma renin activity were measured in blood samples taken in morning hours from the patients in the supine position. The aldosterone to plasma renin activity (A/PRA) and aldosterone to direct renin (A/DR) ratios were calculated. The elevated blood aldosterone level is currently believed to be the principal criterion for primary aldosteronism in the patients suffering arterial hypertension. The RIA technology is the method of choice for the measurement of aldosterone levels. The determination of the A/PR ratio significantly improves the detectability of the disease. The use of direct renin level instead of kinetic renin ensures the high efficacy of screening for primary aldosteronism and its early diagnostics. The cut-off point for the calculation of the A/PRA ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 100%, specificity 97.8%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 49 pmol/mU (sensitivity 100%, specificity 95%). The cut-off point for the calculation of the A/PR ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 89.5%, specificity 99%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 1432 pmol/mcg/hr (sensitivity 89.5%, specificity 100%). It is concluded that the results of determination of direct renin level in the blood plasma are independent of the endogenous angiotensinogen level, less variable and more reproducible than than the results of the measurement of plasma renin activity. The aldosterone to direct renin ratio may be used for the screening of primary aldosteronism.

1090 INTEGRATING GENETICS AND GENOMICS IN PRIMARY ALDOSTERONISM

Primary aldosteronism (PA) is the most common form of endocrine hypertension, due in most cases to aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). Screening for PA is of major importance, given the severe cardiovascular outcome of aldosterone excess that is independent of blood pressure levels. Yet, the pathogenic mechanisms leading to aldosterone hypersecretion and cell proliferation are largely unknown. Transcriptome analyses have highlighted the contribution of different signaling pathways converging upon increased expression of CYP11B2 coding for aldosterone synthase. Less is known with regard to the mechanisms underlying nodulation. Recent evidence indicates a link between APA formation and peritumoral tissue remodelling and ZG hyperplasia with the re-expression of genes involved in foetal adrenal development that could underlie excessive cell proliferation and APA formation. Recently, a few recurrent somatic mutations of the KCNJ5 gene, coding for the potassium channel Kir3.4, have been implicated as a cause of APA, while inherited mutations of the same gene were identified in familial hyperaldosteronism type 3. Somatic KCNJ5 mutations are found in ∼34% of unselected patients with APA; germline KCNJ5 mutations, however, are not similarly causative for BAH. Mutations lie near or within the selectivity filter of the Kir3.4 channel and result in a loss of channel selectivity, with increased sodium conductance leading to membrane depolarization and activation of calcium signaling. While it has been formally established that this cascade of events leads to increased aldosterone production, the mechanisms leading to increased cell proliferation still need to be elucidated.