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Background: Despite hyperaldosteronism being suggested as predisposing to arrhythmias, the relationship between atrial fibrillation and primary aldosteronism remains uncertain. Therefore, we tested the hypothesis that atrial fibrillation is a presentation of primary aldosteronism in hypertensive patients with unexplained atrial fibrillation., Design and Methods: The Prospective Appraisal on the Prevalence of Primary Aldosteronism in Hypertensive (PAPPHY) Study recruited consecutive patients with atrial fibrillation and an unambiguous diagnosis of arterial hypertension at three referral centers for hypertension., Results: In a cohort entailing 411 atrial fibrillation patients, we identified 18% (age 61 ± 11 years; 32% women), who showed no known cause of the arrhythmia. A thorough diagnostic work-up allowed us to identify primary aldosteronism in 73 of these patients, i.e. 42% [95% confidence interval (CI) 31.8-53.9]. Subtyping of primary aldosteronism demonstrated that surgically curable forms of primary aldosteronism accounted for 48% of the cases (95% CI 31.9-65.2). The high prevalence of primary aldosteronism was confirmed at sensitivity analyses., Conclusion: These results provided compelling evidence that primary aldosteronism is highly prevalent in hypertensive patients with unexplained atrial fibrillation. Accordingly, they suggest that patients with no identifiable cause of the arrhythmia should be screened for primary aldosteronism to identify those who can be cured or markedly improved with target treatment. CLINICAL TRIAL REGISTRATION: :: https://clinicaltrials.gov, Identifier: NCT01267747.

Background and Aims: The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension., Methods and Results: From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P < 0.05), 24-h urinary albumin excretion (UAE) (38.8 ±  vs. 7.6 ± mg/24 h; P < 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P < 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC < 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P < 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (<0.9) in essential hypertensive individuals., Conclusion: Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

Background: The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS., Methods and Results: In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively)., Conclusion: Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

Objective: As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS)., Design: Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping., Methods: We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis., Results: We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype., Conclusion: Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

Bipolar disorders are chronic conditions treated with lithium, which exerts deleterious effects on the kidney, among which nephrogenic diabetes insipidus, tubular acidosis and ultimately chronic kidney disease. Conversely, drugs that alter renal function can modify its serum levels and lead to the potentially fatal lithium intoxication. A search in the main library databases from 1975 to 2015 to identify interactions between antihypertensive drugs and lithium using the Population Intervention Comparison Outcome strategy provided only 30 reports of lithium intoxication. A regression analysis showed that the severity of lithium intoxication was significantly predicted by female, age, and use of certain classes of antihypertensive agents. A model including certain albeit not all diuretics and/or inhibitors of the renin-angiotensin system, but not age, serum lithium or creatinine levels at baseline and/or on admission to the hospital, predicted lithium toxicity. The true incidence of lithium intoxication is unknown but probably low, albeit underestimated. Nonetheless, in patients treated with lithium, monitoring of the serum lithium levels and clinical conditions is mandatory after the introduction of antihypertensive drugs, as diuretics and renin-aldosterone system inhibitors.

Case Report: A young patient presented with a history of resistant arterial hypertension, associated with disabling symptoms. He was subjected to an enormous number of tests to identify a pheochromocytoma that was never found. He was eventually discovered to make factitious use of amphetamine to mimic this condition in order to gain medical attention. Munchausen syndrome was thus diagnosed. The patient was discharged and was lost to follow-up until he presented again in 2012 for 'resistant hypertension' in our outpatient clinic. He reported that because of poor blood pressure, he had been referred to a Cardiology department where transcatheter renal denervation was performed with no effect on blood pressure. Thereafter, he was presented to an Endocrinology unit where a left adrenalectomy was performed with diagnosis of pheochromocytoma that was not found at pathology., Discussion: Munchausen syndrome is a rare psychiatric condition that leads affected patients to cause intentionally signs and symptoms of an illness or injury by inflicting medical harm to their body to attract the attention of the physician and get admission to the hospital., Conclusion: To our knowledge, this is the first case of causing drug-resistant hypertension and leading to unnecessary renal denervation and adrenalectomy.