Jorge Gabriel Ruiz-Sánchez

BACKGROUND: Left ventricular hypertrophy (LVH) is frequently identified in patients with primary aldosteronism; determinants of LVH regression after targeted treatment are debated. We assessed LVH prevalence before and after adrenalectomy or mineralocorticoid receptor antagonist (MRA) therapy, identified determinants of LVH regression, and evaluated the relationship between patients’ outcomes and cardiac remodeling. METHODS: We retrospectively analyzed an international cohort of patients with primary aldosteronism from 36 referral centers in Spain, Italy, and Germany. Echocardiographic recordings were included at baseline and after at least 1 year of targeted treatment. Regression models were applied to identify parameters associated with LVH regression and changes in left ventricular mass index. RESULTS: Among 1454 patients (mean age, 51 years; 58.7% men) with primary aldosteronism, baseline LVH prevalence was 49.4%. Aldosterone, blood pressure, male sex, number of antihypertensive medications, and diabetes were associated with LVH. Of 473 patients with follow-up echocardiography, 33.6% underwent adrenalectomy, 61.7% received MRA, and 4.7% were taking MRA postsurgery. After a median follow-up of 51 months, LVH regression was observed in 54.2% of patients (61.9% after adrenalectomy versus 48.6% with MRA treatment; P =0.043), and left ventricular mass index significantly decreased after both surgery and medical therapy. Higher pretreatment blood pressure and aldosterone levels were associated with a lower likelihood of LVH regression, regardless of treatment modality. Complete biochemical success was associated with greater left ventricular mass index reduction at follow-up. CONCLUSIONS: LVH regressed in over half the patients after targeted treatment, with left ventricular mass index decreasing after both adrenalectomy and MRA therapy. Baseline aldosterone levels were associated with LVH regression, independently of blood pressure load.

Background/Objectives: Hypoaldosteronism is classified into “aldosterone deficit” (Aldo-D) and “aldosterone/mineralocorticoid resistance” (Aldo-R) based on etiopathogenic mechanisms. This distinction could be useful for guiding the treatment. However, no reliable methods have been established to differentiate these subtypes. We first aimed to assess whether aldosterone levels could help identify them when assessed in the setting of hyperkalemia or hyperreninemia. Methods: We conducted a retrospective analysis of eighty-four cases of hypoaldosteronism. Aldo-D and Aldo-R classification was based on the presence of clinical factors associated with aldosterone deficit and mineralocorticoid resistance, respectively. The accuracy of plasma aldosterone (PAC) to identify each type of hypoaldosteronism individually was evaluated using AUC-ROC analysis. Results: Aldo-D was identified in 66 (78.6%), and Aldo-R in 41 (48.8%) cases. Factors related to both subtypes were observed in forty-seven (56%) cases. AUC-ROC analysis of PAC measured during hyperkalemia showed low accuracy for detecting either subtype. During hyperreninemia, PAC accuracy was adequate for identifying Aldo-D but unsatisfactory for Aldo-R. Nevertheless, a PAC ≤ 60 pg/mL (6 ng/dL, ~166 pmol/L) during hyperkalemia and hyperreninemia yielded positive predictive values (PPV) of 94% and 100%, respectively, for Aldo-D, while a PAC value > 160 pg/mL (~443 pmol/L), particularly ≥ 200 pg/mL (20 ng/dL, ~550 pmol/L) in either condition had a PPV of 100% for Aldo-R. Conclusions: Although overall diagnostic accuracy was limited, extreme low and high PAC values (≤ 60 pg/mL or ≥ 200 pg/mL) may be suggestive of Aldo-D or Aldo-R, respectively, while intermediate values remain difficult to interpret due to substantial overlap.

Objective: This study aims to analyze current medical management of primary aldosteronism (PA) in Spain, including doses, adverse events (AEs), and efficacy. Methods: SPAIN-ALDO is a national, multicenter, retrospective registry of patients with PA in Spain. For this study, information about medical treatment with mineralocorticoid receptor antagonist (MRA) as first-line or postsurgical therapy and about antihypertensive medications used before PA targeted treatment (MRA or adrenalectomy) was included. We reported surgically and medically treated patients at baseline and at last available follow-up and evaluated clinical and biochemical responses according to Primary Aldosteronism Surgical Outcome (PASO) and Primary Aldosteronism Medical treatment Outcome (PAMO) criteria. Results: A total of 997 patients with PA were included. Before PA diagnosis, the classes of antihypertensive drugs most used were calcium-channel blockers (66%) and angiotensin II receptor blockers (48.4%). Of the initial cohort, 880 patients had at least 1 visit available after initiation of MRA (N = 511 as first-line therapy, N = 47 postsurgery) or adrenalectomy (N = 322). The median defined daily dose of MRA therapy was 1.33. Spironolactone was more prescribed than eplerenone (58% vs 42%). Eplerenone was better tolerated than spironolactone (AEs in 4% vs 18%), particularly among males. After a median follow-up of 35 and 17 months for medically and surgically managed patients, the latter achieved a complete biochemical (68.1%) or clinical (33.6%) response more frequently than people under MRA as first-line therapy (48.6% and 15.7%; P < .001). Conclusion: This study underscores the need to optimize PA medical management in Spain to improve patient clinical and biochemical outcomes, since currently the proportion of patients achieving complete clinical and biochemical response with MRA is quite low.

Background/Objectives: Primary aldosteronism (PA) is associated with a higher cardiovascular disease (CVD) risk than essential hypertension (EH) and is mainly driven by the excess of aldosterone production. Studies suggest a relationship between aldosterone and parathormone (PTH) homeostasis. Excessive PTH levels seem to also be associated with CVD. The impact of PTH levels on CVD in PA patients has not been totally elucidated. We evaluated the associations of PTH levels and hyperparathyroidism with CVD in patients with PA and EH. Methods: A cross-sectional study of a group of 67 patients was carried out, with 35 patients with PA and a control group of 32 patients with EH. We looked at the presence of CVD and data on the factors associated with its presence were collected and analyzed. A binary logistic regression was performed to assess multivariate relationships. Results: PA patients had higher PTH levels compared to the EH group (64 ± 42 vs. 39 ± 13 pg/mL, p = 0.004). Significative differences in PTH levels were observed according to the grade of hypertension in PA patients. Both hyperparathyroidism and CVD were found at higher rates in patients with PA. Patients with CVD exhibited significantly higher PAC values than patients without it (41.4 ± 18 vs. 21.4 ± 12 ng/dL, p < 0.001). Patients with hyperparathyroidism had higher rates of CVD than patients without it (58 vs. 24%, p = 0.018). Patients with PA and hyperparathyroidism manifested a higher rate of CVD than patients without this combination. A logistic regression showed an independent association of PAC and hyperparathyroidism with the presence of CVD in the total cohort. Conclusions: Hyperparathyroidism is associated with a higher probability of CVD both in PA and EH. The presence of hyperparathyroidism in PA seems to exacerbate the risk of CVD, with higher PTH levels associated with higher grades of hypertension in this cohort.

Aim: To evaluate the influence of smoking on cardiometabolic profile and surgical outcomes in patients with primary aldosteronism (PA). Methods: Multicentre retrospective study of patients with PA evaluated in 36 Spanish tertiary hospitals with available information on smoking habits [smokers and non-smokers (never smokers and ex-smokers)]. Results: A total of 881 patients were included, of whom 180 (20.4%) were classified as smokers and 701 as non-smokers. At diagnosis, smokers and non-smokers did not differ in blood pressure or serum potassium levels between. However, smokers had a higher prevalence of left ventricular hypertrophy (LVH) than non-smokers [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.23-3.25], and smokers were more likely to have severe LVH than non-smokers (12.5% vs 6.6%, P = .164). A larger mean tumour size of the adrenal nodule/s was observed in the smoking group (18.6 ± 9.66 vs 15.8 ± 8.66 mm, P = .002). In addition, the odds of mild autonomous cortisol secretion (MACS) was greater in smokers than in non-smokers (OR 2.1, 95% CI 1.14-4.06), but these differences disappeared when adjusted for the size of the adrenal nodule/s (adjusted OR 1.6, 95% CI 0.76-3.37). The rate of biochemical and hypertension cure was similar in both groups; however, hypertension cure tended to be more frequent in the non-smoker group (41.2% vs 29.9%, P = .076). Conclusions: Patients with PA who smoke have a higher prevalence of LVH and MACS and larger adrenal nodule/s than non-smokers. Smoking has no significant effect on the probability of hypertension response after adrenalectomy in patients with PA; however, a tendency to a lower probability of hypertension cure is observed in smokers compared to non-smokers.

Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn’s Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing’s syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance.