J. Deinum

Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism.

Context Primary aldosteronism can involve 1 or both adrenal glands. Surgery is indicated only for unilateral disease. Experts prefer adrenal vein sampling (AVS) to localize the source, but many physicians rely on computed tomography (CT) or magnetic resonance imaging (MRI). Content The authors reviewed 38 studies that compared localization by CT/MRI and AVS. In 37.8% of 950 patients, CT/MRI results disagreed with AVS results. Based on CT/MRI alone, the following would have occurred: surgery for bilateral disease in 14.6% of patients, medical treatment for unilateral disease in 19.1%, and removal of the wrong adrenal in 3.9%. Caution Long-term outcomes, the best indicator of success, were often missing. Implication Because CT/MRI is not reliable, AVS is preferred for staging primary aldosteronism. The Editors Although debate on the true prevalence of primary aldosteronism among the hypertensive population continues, primary aldosteronism is considered a frequent and curable form of hypertension. Depending on the population tested and the tools used to confirm the diagnosis, primary aldosteronism is reported to occur in approximately 5% to 13% of hypertensive patients, predominantly those with severe hypertension (18). Because patients with unilateral adrenal hypersecretion of aldosterone may be cured by unilateral adrenalectomy, differentiating unilateral (most often an adenoma) from bilateral (most often bilateral hyperplasia) aldosterone hypersecretion is important. In patients with bilateral hypersecretion, medical treatment, usually mineralocorticoid-receptor antagonists, is the therapy of choice. In the late 1960s, adrenal vein sampling (AVS) was introduced as a test to distinguish unilateral from bilateral primary aldosteronism (9). Later, computed tomography (CT) and magnetic resonance imaging (MRI) were adopted as the primary procedures with which to differentiate unilateral from bilateral adrenal abnormalities. In a considerable proportion of patients, however, CT and MRI results were found to disagree with those of AVS; CT/MRI would show, for example, a unilateral abnormal adrenal gland when aldosterone hypersecretion actually was occurring in the contralateral gland or bilaterally, or would show bilateral normal or abnormal adrenal glands when aldosterone hypersecretion was occurring in only 1 gland (1014). A recent prospective study of 203 patients showed that operative planning based on anatomical imaging alone would have inappropriately excluded 21.7% of patients from adrenalectomy and would have led to unnecessary sugery in 24.7% (15). Thus, in recent years, AVS has regained popularity. Almost all experts agree that the criterion standard diagnostic test for lateralization of aldosterone secretion is measurement of aldosterone levels in the adrenal veins through AVS (11, 12, 1620). However, AVS has not replaced CT/MRI because it is not universally available and CT/MRI helps the surgeon to accurately localize the adrenal gland. In addition, AVS is a complicated technique with a relatively high chance of procedural failure (for example, when an adrenal vein cannot be adequately cannulated) in inexperienced hands and is more invasive than CT/MRI. Many physicians therefore perform CT/MRI as the first and sometimes only investigation to diagnose laterality of aldosterone secretion. Because misinterpretation of the imaging results could lead to inappropriate treatment, it is essential to know, under the assumption that AVS is the criterion standard test, how often inappropriate treatment decisions would have been made on the basis of CT/MRI findings alone. We performed a systematic literature search and analyzed studies of patients who underwent both techniques. Methods Data Sources and Searches We conducted a systematic search of PubMed, MEDLINE, and EMBASE to find English-, French-, German-, or Dutch-language studies on primary aldosteronism by using the following search terms: ((primary hyperaldosteronism) OR (primary aldosteronism) OR (Conn) OR (hyperaldosteronism) OR (aldosterone-producing adenoma) OR (APA) OR (idiopathic hyperaldosteronism) OR (IHA) OR (primary adrenal hyperplasia) OR (PAH) OR (bilateral adrenal hyperplasia) OR (BAH)) AND ((adrenal venous sampling) OR (AVS) OR (venous sampling) OR (vein sampling) OR (adrenal vein) OR (adrenal venous)). We searched the Cochrane Library using the search string primary hyperaldosteronism or hyperaldosteronism and AVS or adrenal venous sampling for clinical trials published in English, French, German, or Dutch. Searches are up to date through April 2009. We sought to include all studies that performed both AVS and CT/MRI. We assumed that articles that reported on AVS results would also report on CT/MRI findings because CT/MRI is the standard imaging study in patients with primary aldosteronism. Study Selection Two reviewers independently and in duplicate assessed the eligibility of all abstracts. We excluded abstracts if they represented reviews or practice guidelines or if they, with certainty, described only studies in animals or children; patients without primary aldosteronism; or only 1 patient. If we could not make a decision about inclusion solely on the basis of the abstracts, we retrieved and reviewed full-text articles. We considered studies eligible for inclusion if they met the following criteria: 1) original reported results, not previously published or used in earlier studies; 2) adult patients (age> 18 years) with a diagnosis of primary aldosteronism; 3) description of more than 1 patient to avoid publication bias (when only 1 patient is described, there is a high a priori chance that the findings in this patient were unusual, which could imply that such studies are more likely to contain results in which CT/MRI did not agree with AVS results); 4) CT/MRI plus bilateral selective AVS performed in all patients, with the results of both investigations reported; and 5) publication from 1977 onward (CT has been available since that year). We excluded articles if 1) data had already been published (only the most recent publication was used), 2) inclusion bias was suspected because patients with concordant results seemed to have been selectively included or because selective examples of concordant and discordant CT/MRI and AVS results were presumed to have been given, and 3) only discordant results were described. To ensure interobserver consistency, differences in interpretation were resolved by consensus of the 2 reviewers, by group conferences with the other authors, or by referencing the original full-text article. Data Extraction and Quality Assessment We made a database of all studies eligible for inclusion. For each eligible study, we recorded aggregated results for the patients for whom the study reported the following: CT/MRI and AVS results; the techniques of CT, MRI, and AVS (such as slice thickness of the CT/MRI images); use of synthetic adrenocorticotropic hormone (ACTH) during AVS; and the AVS criteria used to determine whether aldosterone secretion was lateralized. For the 950 patients whose CT/MRI and AVS results could be retrieved, we recorded such characteristics as age, sex, blood pressure, and serum potassium level and biochemical variables (such as criteria for diagnosis of primary aldosteronism), as well as treatment strategy and patient follow-up if we could link those characteristics with certainty to these patients. Because the diagnostic criteria for primary aldosteronism differ in their stringency, we subdivided the articles by whether the diagnosis of primary aldosteronism was based on a sodium chloride loading test (the most stringent criterion) or on the aldosteronerenin ratio (less stringent criterion) or plasma aldosterone concentration plus plasma renin activity or plasma renin concentration (less stringent criterion). We also evaluated whether the report mentioned the cutoff value of both the selectivity criterion and the lateralization criterion. The selectivity criterion is used to determine whether blood was drawn selectively from the adrenal veins and not from an adjacent vein; this ratio is calculated for both the left and the right side and is expressed as the CAV/CIVC ratio: [cortisol]adrenal vein/[cortisol]inferior vena cava; when this ratio exceeds a certain arbitrary cutoff value, sampling can be considered selective. The lateralization criterion is used to determine whether aldosterone hypersecretion was unilateral or bilateral by comparing aldosterone and cortisol concentrations in the 2 adrenal veins; this ratio, A/Cips/ACcont, is calculated as [aldosterone]/[cortisol]ipsilateral adrenal vein/[aldosterone]/[cortisol]contralateral adrenal vein (the ipsilateral adrenal vein is the one with the highest [aldosterone]/[cortisol] ratio). When this ratio exceeds a certain arbitrary cutoff value, aldosterone secretion is recorded as lateralized. When we were uncertain about how the authors confirmed the diagnosis of primary aldosteronism, we contacted one of the contributing authors to ask for details about the measurement of aldosterone and renin and whether a sodium chloride loading test had been performed. We also contacted the authors when the article did not specify the criteria used during AVS; of the 31 authors contacted, 22 (71%) responded and 13 (59% of the responders) could provide us with additional information. We excluded articles in which we could not confirm that the authors based the diagnosis of primary aldosteronism on a sodium chloride loading test, aldosteronerenin ratio, or plasma aldosterone concentration plus plasma renin activity. Twenty-one articles reported on the success rate of AVS. Of the 976 procedures performed, 183 were unsuccessful (overall success rate, 81.3%). Data Synthesis and Analysis Assuming AVS is the diagnostic reference criterion test, we analyzed how many times the CT/MRI result agreed or disagreed with the AVS result. The CT/MRI result was considered accurate

Aortic augmentation index and pulse wave velocity in response to head-up tilting: effect of autonomic failure.

Background: Aortic augmentation index (AIx) but not carotid–femoral pulse wave velocity (cfPWV) has reported to decrease in response to vasodilators, which has been related to changes in the timing and/or intensity of wave reflection. Yet, recent evidence indicates that arterial reservoir pressure rather than wave reflection is the most important determinant of AIx. Methods: Using radial artery applanation tonometry and a general transfer function AIx, aortic pulse wave reflection time and cfPWV (foot-to-foot method) were determined in 10 patients with severe autonomic failure and in 14 healthy individuals during supine rest and graded head-up tilting. Results: During supine rest, mean blood pressure (BP) (127.6 ± 21.5 and 97.5 ± 9.4 mmHg), AIx (32.4 ± 13.0 and 23.1 ± 8.7%) and cfPWV (12.1 ± 3.6 and 8.9 ± 1.6 m/s) were higher in patients than in controls. In patients, BP decreased by 18.7 ± 9.8 and 39.6 ± 11.7%, AIx by 39.2 ± 27.5 and 100.9 ± 78.1% and cfPWV by 12.0 ± 10.5 and 27.7 ± 13.5% in response to 30 and 60° head-up tilting. Decreases in AIx and cfPWV correlated with the BP fall (r = 0.67, P = 0.001 and r = 0.75, P < 0.001), but changes in AIx and cfPWV were unrelated. In controls, AIx during head-up tilting decreased despite increases in vascular tone and cfPWV. Aortic reflection time in patients and controls during tilting did not change. Stepwise regression analysis revealed that 68% of the variation in AIx could be explained by the BP fall and reflection time and 76% of the variation in cfPWV by the BP fall and sex. Conclusion: In a clinical model of autonomic failure, both AIx and cfPWV largely depend on instantaneous BP, but these two variables are unrelated, supporting the contention that aortic reservoir pressure rather than wave reflection is the main determinant of AIx.

Does wave reflection explain the increase in blood pressure during leg crossing

ObjectiveTo assess the effect of crossing legs at the knee level on wave reflection, as measured by the augmentation index. MethodsForty-two participants crossed their legs at the knee level (popliteal fossa over the suprapatellar bursa) in the sitting position for 12 min. One trained investigator performed the measurements before, during, and after leg crossing. We used the SphygmoCor to measure the augmentation index at the radial artery and an oscillometric device to measure blood pressure (BP) at the upper arm. We calculated the differences between the uncrossed and the crossed position for the augmentation index normalized for heart rate, peripheral BP, and central BP. ResultsBoth peripheral systolic BP 2.5±6.5 (mean±SD) mmHg (0.5–4.6) (95% confidence interval) and peripheral diastolic BP 1.7±3.8 mmHg (0.5–2.9) increased during leg crossing compared with the uncrossed position. In addition, central systolic BP 2.8±5.8 (0.9–4.6) and central diastolic BP 1.8±3.9 (0.5–3.0) increased, whereas no significant change in the augmentation index was observed. ConclusionOur results indicate that the increase in BP during leg crossing cannot be explained by wave reflection. We found no change in the augmentation index during leg crossing at the knee level. Central BP and peripheral BP are equally influenced by leg crossing.

[OP.6B.04] DEVELOPMENT OF A PREDICTION MODEL FOR PATIENTS WITH SUSPECTED PRIMARY ALDOSTERONISM AND AN INCONCLUSIVE SALT LOADING TEST

Objective: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT). Design and method: Our retrospective cohort comprised patients who underwent an SLT between 2005 and 2016 in our university medical center. We included 290 patients. The SLT was inconclusive (post-infusion aldosterone levels 140–280 pmol/L) in 115 patients. In 45/115 PA was present according to an expert meeting. Together with 101 patients with a positive SLT result this resulted in a total of 146/276 (missing data in n = 14) patients with PA. We used binary logistic regression analysis to identify variables independently associated with PA. Results: The decision model contained the following continuous variables increasing the likelihood of PA: low plasma renin concentration (PRC) before SLT, high plasma aldosterone concentration (PAC) after SLT, high potassium supplementation, and low plasma potassium concentration.1 In patients with an inconclusive SLT the model had a sensitivity of 84.4% and a specificity of 94.3%. The positive and negative predictive value were 90.5% and 90.4% respectively. 1Prediction score (p)† = ebx / (1+ebx) Where bx = 0.55– 0.290*PRC before saline infusion (mU/l) + 0.05*PAC after saline infusion (pmol/l) + 0.07*potassium supplementation prior to SLT (mmol/day) −2.75*plasma potassium concentration prior to SLT (mmol/l) †p > 0.59 indicates PA Conclusions: Our model may be helpful in deciding how to manage PA patients with an inconclusive SLT. External validation and prospective studies are necessary before implementing this model in clinical practice.

[PP.27.07] QUALITY OF LIFE IN PRIMARY ALDOSTERONISM IMPROVES MORE AFTER ADRENALECTOMY THAN AFTER MEDICAL THERAPY

Objective: To compare the effects of surgical and medical treatment on health-related quality of life (QoL) in primary aldosteronism Design and method: We did a post-hoc comparative effectiveness study within the SPARTACUS trial (n = 184) in thirteen hospitals. In case of aldosterone-producing adenoma we performed an adrenalectomy and for bilateral adrenal hyperplasia we treated patients with mineralocorticoid receptor antagonists. At baseline, six months and one year follow-up we assessed QoL by two validated questionnaires. Results: At baseline, seven out of eight RAND SF-36 subscales and both summary scores and three out of five EQ-5D dimensions and the visual analogue scale were lower in PA patients compared to the general population. The beneficial effects of adrenalectomy were larger than for mineralocorticoid receptor antagonists for seven RAND SF-36 subscales, both summary scores, and health change. For the EQ-5D, we detected a difference in favour of adrenalectomy in two of the five dimensions and the visual analogue scale. Most differences in QoL between both treatments exceeded the minimally clinically important difference. After one year we observed improvement of most QoL measures for both treatments, but only for adrenalectomy all returned to the level of the general population. Conclusions: Both treatments clearly improve QoL of patients with PA, underscoring the importance of identifying these patients. Improvement in QoL in patients with PA one year after surgical treatment for suspected aldosterone-producing adenoma is superior to that of medically treated patients with suspected bilateral adrenal hyperplasia.

Should blood pressure be measured with the cuff on a bare arm

ObjectiveTo establish whether the results of blood pressure (BP) measurements are affected by wearing clothing underneath the BP cuff during measurement. MethodsNormotensive and hypertensive patients (n=133; 65 men) of an outpatient clinic participated in this study. BP was measured according to a rigorous protocol with a validated oscillometric device under three conditions: with one layer of own clothing (OC) underneath the cuff, with one layer of standardized clothing (SC) underneath the cuff, and with the cuff on a bare arm (BA), in a randomized order. Patients were seated on a chair with their right arm on the table and their feet flat on the floor during BP measurement. ResultsThe mean BP values (±SEM) measured during BA, OC, and SC were, respectively, 132.8±1.3, 132.3±1.4, and 133.2±1.4 mmHg for systolic blood pressure (SBP), 78.3±0.9, 78.3±0.9, and 78.5±0.9 mmHg for diastolic blood pressure (DBP), and 90.3±1.0, 90.0±1.0, and 91.5±1.0 mmHg for mean arterial blood pressure (MAP). The differences in SBP, DBP, and MAP between BA, OC, and SC measurements were not statistically significant, but there was considerable intraindividual variation in SBP deviations of more than 5 mmHg between BA versus OC and SC. There was no significant order effect of the three conditions. The absence of differences between BA, OC, and SC was not determined by age, sex, BMI, and arm circumference. ConclusionWe could not find differences in MAP, SBP, and DBP between the bare and clothed arms, but intraindividual variation of SBP between the three conditions is not negligible. Despite this caveat, these data suggest that in an outpatient clinic, BP can be measured reliably with one layer of clothing underneath the cuff. This is timesaving and more comfortable for patients.

4 Secundaire hypertensie

In dit hoofdstuk worden de belangrijkste vormen van secundaire hypertensie besproken. In de huisartsenpraktijk heeft naar schatting 5 procent van de hypertensieve populatie een secundaire hypertensie.

THE EFFECT OF CROSSING THE ANKLE OVER THE KNEE ON BLOOD PRESSURE: PP.14.08

Background: Crossing the ankles in the sitting position has no effect on blood pressure (BP), but BP increases when legs are crossed at the knee level. The physiological mechanism responsible for this BP increase is a higher cardiac output (CO), but not a higher total peripheral resistance (TPR). Objective: The purpose of our study was to determine the effect and physiological mechanism of crossing the ankle over the knee on BP. Methods: Finger BP was measured continuously and noninvasively by the use of the Nexfin monitor by one trained investigator. Twenty five participants crossed their ankle over the knee with the lateral malleolus on the suprapatellar bursa in the sitting position. Differences in systolic BP (SBP), diastolic BP (DBP), mean BP (MAP), heart rate (HR), stroke volume (SV), CO and TPR were determined in the crossed position versus feet flat on the floor. Results: Except TPR, all hemodynamic parameters were significantly higher with the ankle crossed over the knee versus the uncrossed position: SBP 11.4 ± 5.3 mmHg (mean ± SD) (9.2–13.6; 95% CI), DBP 3.8 ± 2.5 mmHg (2.8 – 4.9), MAP 7.0 ± 3.9 mmHg (5.4 – 8.6), HR 1.7 ± 3.2 beats/min (0.4 – 3.0), SV 5.7 ± 3.7 ml (4.2 - 7.3), CO 0.5 ± 0.3 l/min (0.4 – 0.7). Conclusion: Our study shows that ankle crossing over the knee causes increases in BP, CO and SV, while TPR does not change. The working mechanism for the BP increase when the ankle is crossed over the knee seems to be comparable with the working mechanism of the BP increase when legs are crossed at knee level. All persons who measure BP should be aware of the influence of leg position and instruct patients to keep their feet flat on the floor during BP measurements. The position of legs should be mentioned in all guidelines and publications regarding BP.

SHOULD MANAGEMENT OF PRIMARY ALDOSTERONISM BE BASED ON ADRENAL VEIN SAMPLING OR ADRENAL CT-SCAN? A RETROSPECTIVE STUDY OF BLOOD PRESSURE, MEDICATION USE, POTASSIUM AND ALDOSTERONE: PP.18.183

Background: Adrenal vein sampling (AVS) and adrenal CT-scan (CT) can distinguish aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) as causes of primary aldosteronism (PA). However, these diagnostics are discordant in up to 40% of cases (1). To judge the best technique to subtype PA we studied outcome during follow-up of PA patients that have been diagnosed by either AVS or CT. Methods: We studied retrospectively 123 patients with PA, who underwent conclusive AVS (n = 60) or CT (n = 63). CT-based management was chosen because AVS was not yet available (before 2004) or because AVS had failed. Evaluation was at baseline and 3 months after intervention (adrenalectomy for APA or medical treatment for BAH). Relevant outcomes were blood pressure (SBP and DBP), daily defined dosages of antihypertensive drugs (DDD), random plasma aldosterone levels ([aldo] nmol/L, not for patients on medical treatment), and potassium levels ([K] mmol/L). Results: Both groups had similar ages (mean (range) 52 (23–72) and 51 (28–77) years for AVS and CT resp.) Discordance between AVS and CT was 32%, confirming the literature. Blood pressure was lower 3 months after intervention in the AVS-group, but antihypertensive use was higher (see table). Figure 1. No caption available. Limitations: This is a retrospective, observational study; data on potassium and aldosterone levels were incomplete. No salt suppression test was performed after intervention and data on quality of life are not available. Discussion: This black box approach suggests that CT-scan is not inferior to AVS in spite of the discordance in diagnosis between AVS and CT. This suggests that AVS may not be as infallible as assumed. However, we cannot exclude that the quality of life is better for patients that have undergone successful AVS. In view of the costs and complexity of AVS, the results call for a prospective study that compares CT- and AVS based management.

Is bloeddruk meten aan niet-ontklede arm mogelijk?

De bloeddruk is een van de factoren die het cardiovasculaire risicoprofiel van een patient bepaalt. Daarom is het van belang een juiste bloeddrukmeting uit te voeren. Richtlijnen geven aan dat de bloeddruk aan de blote bovenarm gemeten dient te worden. In de praktijk wordt de bloeddruk uit tijdgebrek vaak over een laag kleding gemeten. De vraag luidt of deze laag kleding invloed heeft op de uitkomst van de bloeddrukmeting.