Denis Rossato

Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes.

CONTEXT In patients with primary aldosteronism (PA), it is fundamental to distinguish between subtypes that benefit from different therapies. Computed tomography (CT) scans lack sensitivity and specificity and must be followed by adrenal venous sampling (AVS). Because AVS is not widely available, a list of clinical criteria that indicate the presence of an aldosterone-producing adenoma (APA) has been suggested. OBJECTIVE AND DESIGN The objective of the study was to test the sensitivity and specificity of the last generation CT scans, test prospectively the usefulness of clinical criteria in the diagnosis of APA, and develop a flow chart to be used when AVS is not easily available. SETTING Hypertensive patients referred to our hypertension unit were included in our study. PATIENTS Seventy-one patients with confirmed PA participated in our study. INTERVENTION All patients had a CT scan and underwent AVS. MAIN OUTCOME MEASURE Final diagnosis of APA was the main measure. RESULTS A total of 44 and 56% of patients were diagnosed as having an APA and a bilateral adrenal hyperplasia (BAH), respectively. Twenty percent of patients with PA displayed hypokalemia. CT scans displayed a sensitivity of 0.87 and a specificity of 0.71. The posture test displayed a lower sensitivity and specificity (0.64 and 0.70, respectively). The distribution grades of hypertension were not significantly different between APA and BAH. Biochemical criteria of high probability of APA displayed a sensitivity of 0.32 and a specificity of 0.95. CONCLUSIONS This study underlines the central role of AVS in the subtype diagnosis of PA. The use of the clinical criteria to distinguish between APA and BAH did not display a satisfactory diagnostic power.

Impact of Different Diagnostic Criteria During Adrenal Vein Sampling on Reproducibility of Subtype Diagnosis in Patients With Primary Aldosteronism

In patients with primary aldosteronism, adrenal vein sampling (AVS) is considered the only reliable technique to distinguish between unilateral and bilateral autonomous production of aldosterone, but agreement is lacking on the best criteria indicating successful cannulation and lateralization. The objective of this study was to assess the impact of differing criteria for the successful cannulation and lateralization on the reproducibility of subtype diagnosis. Sixty-two patients with confirmed primary aldosteronism underwent AVS on 2 separate occasions, because the first was unsatisfactory. We compared the different diagnoses of primary aldosteronism subtype reached using AVS data assessed by permissive (type 1), intermediate (type 2), and strict (type 3) criteria. Although 91.1% of all of the (both first and second) AVSs were “successful” by type 1 criteria (50.8% by type 2 and 33.9% by type 3), in only 35.3% of patients was the diagnosis concordant between the first and second AVS. Type 1 criteria also led to a higher rate of diagnosis of unilateral primary aldosteronism (67.3% of successful procedures) than type 2 (36.5%) or type 3 (26.2%). There was considerable disparity in the diagnosis reached using the 3 different criteria, with concordance in only 32.2%. Using either type 1 or 2 criteria, the minimal adrenal/peripheral vein cortisol ratio necessary to obtain the same diagnosis in the first and second AVS procedures was ≥2.75. In conclusion, permissive criteria for successful cannulation and lateralization on AVS achieve poor diagnostic reproducibility and should be avoided.

Adrenal vein sampling in primary aldosteronism: towards a standardised protocol

Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria. In this Personal View, we address several questions that clinicians are presented with when considering adrenal vein sampling. For each of these questions we provide responses based on the available evidence, and opinions based on our experience. In particular, we discuss the most appropriate way to prepare the patient, whether adrenal vein sampling can be avoided for some subgroups of patients, the use of ACTH (1-24) during the procedure, the most appropriate criteria for interpretation of adrenal vein cannulation and lateralisation, the use of contralateral suppression, and strategies to improve success rates of adrenal vein sampling in centres with little experience.

Captopril Test Can Give Misleading Results in Patients With Suspect Primary Aldosteronism

To the Editor: Primary aldosteronism (PA) has emerged as the most common form of secondary hypertension.1 The widespread use of the plasma aldosterone/plasma renin activity ratio as a screening test for both hypokalemic and normokaliemic hypertensive subjects has allowed the demonstration of a high prevalence of this disease, with PA accounting for up to 5% to 10% of all hypertensive patients.1,2 The diagnosis of PA is of particular importance for the clinician, because it has been demonstrated recently that patients with PA are more prone to cardiovascular and cerebrovascular complications, and to target organ damage compared with essential hypertensive subjects with similar risk profiles.3 A positive plasma aldosterone concentration/plasma renin activity ratio should always be followed by a suppression test to definitively confirm the diagnosis. The confirmatory diagnosis is usually made with a saline load test (SLT; oral or intravenous) or with the fludrocortisone suppression test (FST).1 Confirmation of the diagnosis of PA should subsequently undergo a …

Aldosterone Suppression on Contralateral Adrenal During Adrenal Vein Sampling Does Not Predict Blood Pressure Response After Adrenalectomy

CONTEXT Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. OBJECTIVE The objective of the study was to retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. SETTING The study was carried out in eight different referral centers in Italy, Germany, and Japan. PATIENTS From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. RESULTS Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared with basal procedures (90% vs 77%). The CL ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P = .02 and P = .01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters, and patients with CL suppression underwent a significantly larger reduction in the aldosterone levels after adrenalectomy. CONCLUSIONS For patients with lateralizing indices of greater than 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.

Left-sided portal hypertension: Successful management by laparoscopic splenectomy following splenic artery embolization

INTRODUCTION Left-sided portal hypertension is a rare clinical condition most often associated with a pancreatic disease. In case of hemorrhage from gastric fundus varices, splenectomy is indicated. Commonly, the operation is carried out by laparotomy, as portal hypertension is considered a relative contraindication to laparoscopic splenectomy (LS). Although some studies have reported the feasibility of the laparoscopic approach in the setting of cirrhosis-related portal hypertension, experience concerning LS in left-sided portal hypertension is lacking. PRESENTATION OF CASE A 39-year-old man was admitted to the Emergency Department for haemorrhagic shock due to acute hemorrhage from gastric fundus varices. Diagnostic work up revealed a chronic pancreatitis-related splenic vein thrombosis causing left-sided portal hypertension with gastric fundus varices and splenic cavernoma. Following splenic artery embolization (SAE), the case was successfully managed by LS. DISCUSSION The advantages of laparoscopic over open splenectomy include lower complication rate, quicker recovery and shorter hospital stay. Splenic artery embolization prior to LS has been used to reduce intraoperative blood losses and conversion rate, especially in complex cases of splenomegaly or cirrhosis-related portal hypertension. We report a case of complicated left-sided portal hypertension managed by LS following SAE. In spite of the presence of large varices at the splenic hilum, the operation was performed by laparoscopy without any major intraoperative complication, thanks to the reduced venous pressure achieved by SAE. CONCLUSION Splenic artery embolization may be a valuable adjunct in case of left-sided portal hypertension requiring splenectomy, allowing a safe dissection of the splenic vessels even by laparoscopy.

Diagnosis of Surgically-Treatable Forms of Primary Aldosteronism

Primary aldosteronism (PA) is a common form of endocrine hypertension in which aldosterone production is inappropriate and at least partially autonomous of the renin-angiotensin system. Recent studies using the plasma aldosterone/plasma renin activity (PRA) ratio (ARR) as a screening test for both hypokalaemic and normokalaemic hypertensives have reported a high prevalence of this disease, with PA accounting for up to 12% of hypertensive patients. Therefore, PA is considered the most common identifiable, specifically treatable and potentially curable form of hypertension. Of particular interest is the identification of the different subtypes of PA, since some of them benefit from surgical treatment, whereas others require medical treatment with mineralocorticoid receptor antagonists. Herein, we review the diagnostic strategies used to identify surgically-treatable forms of PA, i.e. those forms that display unilateral secretion of aldosterone and benefit from unilateral adrenalectomy. In particular, we compare the different imaging strategies, the role of hormonal tests and the indication and interpretation of adrenal venous sampling.

Subtype Diagnosis of Primary Aldosteronism: Approach to Different Clinical Scenarios

Identification and management of patients with primary aldosteronism are of utmost importance because it is a frequent cause of endocrine hypertension, and affected patients display an increase of cardio- and cerebro-vascular events, compared to essential hypertensives. Distinction of primary aldosteronism subtypes is of particular relevance to allocate the patients to the appropriate treatment, represented by mineralocorticoid receptor antagonists for bilateral forms and unilateral adrenalectomy for patients with unilateral aldosterone secretion. Subtype differentiation of confirmed hyperaldosteronism comprises adrenal CT scanning and adrenal venous sampling. In this review, we will discuss different clinical scenarios where execution, interpretation of adrenal vein sampling and subsequent patient management might be challenging, providing the clinician with useful information to help the interpretation of controversial procedures.

Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion.

OBJECTIVE In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. DESIGN Retrospective, cross-sectional study. METHODS The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. RESULTS PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. CONCLUSIONS This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary?

Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery. Despite significant advances in the optimization of the AVS procedure and the interpretation of hormonal data, a standardized protocol across centers is still lacking. Alternative methods are sought to either localize an aldosterone producing adenoma or to predict the presence of unilateral disease and thereby substantially reduce the number of patients with PA who proceed to AVS. In this review, we summarize the recent advances in subtyping PA for the diagnosis of unilateral and bilateral disease. We focus on the developments in the AVS procedure, the interpretation criteria, and comparisons of the performance of AVS with the alternative methods that are currently available.