Paragangliomas and pheochromocytomas are rare neuroendocrine tumors, carrying a germ-line mutation in 40 paragangliomas than in pheochromocytomas; tumor sclerosis, M-GAPP and VMAT1 scores were associated to germ-line mutations. Sclerosis might represent a histological marker of tumor susceptibility, prompting to genetic investigations in paragangliomas.

Professor Antonio Salvetti passed away on 18 February 2021, at the age of 84 years. We express our deepest condolences to his wife, children and grandchildren. Professor Salvetti was born in Lerici, a village at the border between Liguria and Tuscany, on 4 December 1936. He obtained his medical degree at the University of Pisa in 1960 and the Postgraduate Speciality in Cardiology at the University of Turin, 2 years later. After completing his studies, he was immediately asked to join the staff of the Division of Internal Medicine of the Medical School and the Santa Chiara Hospital of the University of Pisa, which was then under the Chairmanship of Professor Fabio Tronchetti. In that Division, he has worked for his entire academical carrier, starting as a young ‘voluntary’ assistant and climbing all steps of the academical ladder up to the position of Full Professor of Medical Therapy in 1984 and then Full Professor of Internal Medicine in 1990. Over his long and productive clinical, teaching and scientific activity, he was appointed Director of the Department of Internal Medicine (2000–2008), Director of the Postgraduate School of Internal Medicine, Director of the Division of General Medicine of the newly formed Azienda Ospedaliero-Universitaria Pisana and Director of the Hospital Department of Medicine from 2001 to his retirement in 2007. Antonio Salvetti was an expert clinician, which made him a reference figure among the hospital doctors when help was needed to resolve difficult clinical cases. However, there is no question that his clinical and scientific preference was directed, since almost the beginning of his carrier, to hypertension where he achieved national and international recognition. In 1980, Professor Salvetti founded the Center for Diagnosis and Treatment of Hypertension, which over the years became a Regional Reference Center and a European Excellence Center for the Diagnosis and Treatment of this condition, being ranked fourth among all European Hypertension Centers for the quality of scientific research. He was a founding member of the Italian Society of Nephro-Cardiology and of the Italian Society of Hypertension for which he served for several years first as Secretary and then as President. He was part of the group, which decades ago gave birth to the World Hypertension League, translating into reality an idea of professor Bartorelli from Milan and Dr Strasser from WHO. He received the Award of the Italian Society of Hypertension for excellence in research on hypertension in 2000 and was awarded in 2007, the prestigious Cherubino Honor for scientific merits by the University of Pisa. He was also appointed Professor Emeritus of the University of Cordoba (Argentina) in 2001. He has often been an invited lecturer at international Meetings on hypertension, those organized by the International and the European Societies of Hypertension, in particular. The sharpness and directness of his criticism made him an especially desired participant in debates, which the audience enjoyed very much. The scientific interests of Professor Salvetti covered the pathogenetic mechanisms of arterial hypertension, with special attention to the role of the renin--angiotensin system, the endothelial dysfunction and the vascular and cardiac structural alterations related to this disease. Many of his observations were pioneering at the time they were made, as also testified by publication of his articles (over 400) in prestigious international peer-reviewed journals. Professor Antonio Salvetti was a person of great scientific and clinical knowledge and depth of thinking. In the fields he was involved with as an investigator, he was a forerunner and exhibited a translational approach that always aimed at finding a relationship between clinical investigations in humans and experimental models of hypertension. His passion for medical research was contagious and passed onto many medical students and colleagues. At clinical level, he blended his wide medical culture with daily clinical practice, in which he displayed the ability to listen and interpret the patient symptoms, ultimately resulting in precise diagnoses and tailored therapeutic decisions. Nothing was ever left to chance by him when patients were involved, and above all, every decision had to be substantiated by solid clinical and scientific evidence. Professor Salvetti was not known to be an easily approachable person, and people were sometimes a bit disconcerted by his competitiveness and directness. Behind the appearance, however, he was a very generous man, ready to understand the problems of those who turned to him and to help them whenever this was possible. He had three great passions: family, work and sport. He considered the sport as a serious affair on which to translate his view of work as something requiring the best of yourself and all efforts to win the confrontation. However, he used in sport what he did in life, that is, the moral values of loyalty, sincerity and extreme correctness. There is no doubt that Antonio Salvetti has been an example, a leader and a teacher to people around him. Not only he introduced the study of arterial hypertension in Pisa, founding one of the most important clinical hypertension centers in Italy, but he was able to create a stimulating scientific environment for his young collaborators, providing them with the opportunity to fully exploit their clinical and research potentialities. Although he has left us, the cultural and scientific heritage he was able to create will not be lost.ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

BACKGROUND:The expression of vesicular catecholamine transporters (VMAT1 and 2) in pheochromocytomas (PHEOs) and paragangliomas (PGLs) and the possible relationships with [18F]FDOPA PET/CT and [123I]MIBG scintigraphy uptake are unknown. Our purpose was to investigate possible correlations of either VMAT1 and VMAT2 expression with the functional imaging in patients with PHEOs and PGLs.METHODS:An observational 3-year time study was performed by enrolling 31 consecutive patients with PHEO (N.=17) or PGL (N.=14). They underwent the same diagnostic work-up; moreover, [123I]MIBG SPECT/CT (N.=20) and [18F]FDOPA PET/CT (N.=14) were performed in a subset of patients. After surgery, routine histology and semiquantitative analysis of VMAT1/VMAT2 immunoreactivity were carried out in all cases.RESULTS:VMAT1 immunoreactivity was found in all tumors, but two PHEOs. VMAT1 immunoreactivity was higher in PGLs than in PHEOs, though at not significant extent. Elevated VMAT2 immunoreactivity score was present in all but two negative tumors. Normal [123I]-MIBG uptake was independent from VMAT1/2 immunoreactivity. Patients undergoing [18F]FDOPA PET/CT showed a high score level of both VMATs and were detected by the technique in all cases.CONCLUSIONS:VMAT1 and VMAT2 are highly expressed in most tumors, though VMAT1 immunoreactivity is apparently prevalent in PGLs as compared to PHEOs. Presence and expression of VMAT1 and VMAT2 are not limiting factors for MIBG uptake. The status of VMAT expression might help to understand why the more frequently used radiotracers do not always have the expected diagnostic performance. Finally, the present study points out the importance of developing new radiotracers with higher sensitivity, specificity and accuracy consequently reducing healthcare costs.

ANZ Journal of SurgeryVolume 91, Issue 9 p. 1655-1658 PERSPECTIVE Indocyanine green fluorescence: an additional tool for endoscopic adrenalectomy Leonardo Rossi MD, Leonardo Rossi MD Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy Contribution: ​Investigation, Writing - original draftSearch for more papers by this authorLorenzo Fregoli MD, PhD, Lorenzo Fregoli MD, PhD Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy Contribution: Conceptualization, ValidationSearch for more papers by this authorAlessandra Bacca MD, Alessandra Bacca MD Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Contribution: ​Investigation, ValidationSearch for more papers by this authorSohail Bakkar MD, Sohail Bakkar MD Department of Surgery, Faculty of Medicine, The Hashemite University, Zarqa, Jordan Contribution: ValidationSearch for more papers by this authorGiampaolo Bernini MD, Giampaolo Bernini MD Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Contribution: ValidationSearch for more papers by this authorGabriele Materazzi MD, Gabriele Materazzi MD orcid.org/0000-0002-3040-516X Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, ItalySearch for more papers by this author Leonardo Rossi MD, Leonardo Rossi MD Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy Contribution: ​Investigation, Writing - original draftSearch for more papers by this authorLorenzo Fregoli MD, PhD, Lorenzo Fregoli MD, PhD Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy Contribution: Conceptualization, ValidationSearch for more papers by this authorAlessandra Bacca MD, Alessandra Bacca MD Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Contribution: ​Investigation, ValidationSearch for more papers by this authorSohail Bakkar MD, Sohail Bakkar MD Department of Surgery, Faculty of Medicine, The Hashemite University, Zarqa, Jordan Contribution: ValidationSearch for more papers by this authorGiampaolo Bernini MD, Giampaolo Bernini MD Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Contribution: ValidationSearch for more papers by this authorGabriele Materazzi MD, Gabriele Materazzi MD orcid.org/0000-0002-3040-516X Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, ItalySearch for more papers by this author First published: 10 September 2021 https://doi.org/10.1111/ans.16725Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume91, Issue9September 2021Pages 1655-1658 RelatedInformation

A 43-years old woman was diagnosed an adrenocortical carcinoma (AC) that was excised, whereas two lung metastases were un-operable. Mitotane 6 g/day was started as standard therapy but it was responsible for severe central nervous system (CNS) and gastrointestinal toxicities associated with a 10 kg body weight loss. A therapeutic drug monitoring (TDM) protocol demonstrated that mitotane plasma concentrations (>30 mg/L) exceeded the therapeutic range (14-20 mg/L) and increased even when drug daily dose was reduced by 50%. The increase in drug plasma concentrations was probably due to body slimming. Under continuous TDM control, a reduced mitotane dose (1.5 g/day) was definitively administered and it proved to be tolerable and effective. Indeed, lung metastases were excised and two years later there was no evidence of other neoplastic lesions. In conclusion, the adoption of therapeutic mitotane monitoring allowed the treatment of an AC patient with a reduced, tolerable and effective dose.

Primary aldosteronism (PA) causes cardiovascular damage in excess to the blood pressure elevation, but there are no prospective studies proving a worse long-term prognosis in adrenalectomized and medically treated patients. We have, therefore, assessed the outcome of PA patients according to treatment mode in the PAPY study (Primary Aldosteronism Prevalence in Hypertension) patients, 88.8% of whom were optimally treated patients with primary (essential) hypertension (PH), and the rest had PA and were assigned to medical therapy (6.4%) or adrenalectomy (4.8%). Total mortality was the primary end point; secondary end points were cardiovascular death, major adverse cardiovascular events, including atrial fibrillation, and total cardiovascular events. Kaplan–Meier and Cox analysis were used to compare survival between PA and its subtypes and PH patients. After a median of 11.8 years, complete follow-up data were obtained in 89% of the 1125 patients in the original cohort. Only a trend ( P =0.07) toward a worse death-free survival in PA than in PH patients was observed. However, at both univariate (90.0% versus 97.8%; P =0.002) and multivariate analyses (hazard ratio, 1.82; 95% confidence interval, 1.08–3.08; P =0.025), medically treated PA patients showed a lower atrial fibrillation–free survival than PH patients. By showing that during a long-term follow-up adrenalectomized aldosterone-producing adenoma patients have a similar long-term outcome of optimally treated PH patients, whereas, at variance, medically treated PA patients remain at a higher risk of atrial fibrillation, this large prospective study emphasizes the importance of an early identification of PA patients who need adrenalectomy as a key measure to prevent incident atrial fibrillation.

Context: Maffucci syndrome is a rare, nonhereditary, mesodermal dysplastic disease characterized by the presence of multiple hemangiomas and enchondromas.This pathological condition, which is often unrecognized, is associated with a high prevalence of benign and malignant endocrine tumors involving pituitary, adrenal, thyroid, and parathyroid glands.Case Description: We describe the case of a young patient presenting a history suggestive of secondary arterial hypertension and typical features of Maffucci syndrome (multiple hemangiomas and enchondromas), which were unrecognized over the previous 3 decades.Given that endocrine diseases are common causes of secondary arterial hypertension and are often associated with Maffucci syndrome, a comprehensive diagnostic workup was performed, revealing the presence of large bilateral adrenal masses (70 mm right, 35 mm left) and autonomous cortisol secretion (adrenocorticotropic hormone-independent Cushing syndrome).The patient underwent a bilateral adrenalectomy, and steroid replacement therapy was initiated.Surgery resulted in a normalization of arterial blood pressure, and antihypertensive treatment was discontinued.Histological examinations revealed morphological features of primary bilateral macronodular adrenal hyperplasia.Conclusions: Early recognition and lifelong monitoring of Maffucci syndrome is required to identify and treat possible associated endocrine diseases and malignancies.Among them, unilateral cortical adrenal masses have been previously described, but to our knowledge, this is the first reported case of Maffucci syndrome associated with primary bilateral macronodular adrenal hyperplasia.Additional studies are needed to establish the etiopathological link between these 2 entities and, more in general, between Maffucci syndrome and endocrine diseases, but possible common genetic alterations may be suggested.

OBJECTIVE:We aimed at developing and validating a simple, highly repeatable computer-based tool, which could be employed to simulate the effects of an acute mental stress on endocrine and haemodynamic stress responses.METHODS:Fifteen subjects underwent a mental cognitive challenge, employing an ad hoc designed web tool (available at http://bagame.altervista.org) that proposed a series of random arithmetic operations (addictions or subtractions) between one- to three-digit numbers for 10 minutes. We measured plasma epinephrine, norepinephrine, cortisol, and ACTH, in addition to heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure throughout the test.RESULTS:The arithmetic mental challenge promptly activated the sympatho-adrenomedullary axis (epinephrine +112±24%, p<0.05; norepinephrine +37±13%, p<0.004) and the hypothalamic-pituitary-adrenocortical axis (cortisol +25±7%, p<0.008; ACTH +97±44%, p<0.008), which in turn exerted stimulatory effects on the cardiovascular system (HR +18±4%, p<0.05; SBP +112±24%, p<0.05; DBP +34±8%, p<0.05) in all subjects, without any symptoms and regardless of the individuals' mental arithmetic ability.CONCLUSIONS:We developed and validated a computer-based tool that is effective for simulating endocrine and haemodynamic responses to an acute mental stress. This novel tool is easy-to-use, freely-accessible, and it can be employed to further investigate stress-related pathophysiological mechanisms and their role in cardiovascular diseases.

Cushing's Syndrome (CS) is associated with a specific spectrum of dementia-like symptoms, including psychiatric disorders, such as major depression, anxiety and mania, and neurocognitive alterations, like impairment of memory and concentration. This pattern of clinical complications, which significantly impair the health-related quality of life of CS patients, is sometimes referred to as "steroid dementia syndrome" (SDS). The SDS is the result of anatomical and functional anomalies in brain areas involved in the processing of emotion and cognition, which are only partially restored after the biochemical remission of the disease. Therefore, periodical neuropsychiatric evaluations are recommended in all CS patients, and a long-term follow-up is required after normalization of hypercortisolism. Recent evidences demonstrate that three classes of drugs (glucocorticoid receptor antagonists, steroidogenesis inhibitors, and pituitary tumor-targeted drugs), which are used for medical treatment of CS, can rapidly relief neuropsychiatric symptoms of SDS. Furthermore, several psychoactive medications have demonstrated effectiveness in the treatment of symptoms induced by the acute or chronic glucocosteroid administration. In this paper, a review of the current and future patents for the treatment and prevention of CS and SDS will be presented.

Cushing's Syndrome (CS) is associated with a specific spectrum of dementia-like symptoms, including psychiatric disorders, such as major depression, anxiety and mania, and neurocognitive alterations, like impairment of memory and concentration. This pattern of clinical complications, which significantly impair the health-related quality of life of CS patients, is sometimes referred to as "steroid dementia syndrome" (SDS). The SDS is the result of anatomical and functional anomalies in brain areas involved in the processing of emotion and cognition, which are only partially restored after the biochemical remission of the disease. Therefore, periodical neuropsychiatric evaluations are recommended in all CS patients, and a long-term follow-up is required after normalization of hypercortisolism. Recent evidences demonstrate that three classes of drugs (glucocorticoid receptor antagonists, steroidogenesis inhibitors, and pituitary tumor-targeted drugs), which are used for medical treatment of CS, can rapidly relief neuropsychiatric symptoms of SDS. Furthermore, several psychoactive medications have demonstrated effectiveness in the treatment of symptoms induced by the acute or chronic glucocosteroid administration. In this paper, a review of the current and future patents for the treatment and prevention of CS and SDS will be presented.

Over recent years, invasive hypertension treatments have led to a new clinical condition, called device-resistant hypertension (DRH).1 DRH is defined as blood pressure (BP) >140/90 mm Hg, with at least 3 antihypertensives at maximal doses, including a diuretic,2 without BP decrease after the invasive treatments. These patients are not infrequent and are obliged to visit several hypertension units for managing their BP. We have observed a significant BP decrease only by using intravenous drugs recommended for emergencies.2,3 Thus, we refined a protocol to perform a chronic intravenous antihypertensive infusion in patients with DRH via an elastomeric pump and a peripherally inserted central catheter (PICC). After exclusion of several intravenous drugs for contraindications, urapidil was selected as the drug of choice. Here, we present the case of the first treated patient with DRH. The patient is a 45-year-old male. He was hypertensive and undergoing treatment since 2009. He was overweight (body mass index, 29.6), a smoker and dyslipidaemic. In 2012, he underwent percutaneous transluminal coronary angioplasty plus stenting for unstable angina and underwent a further new percutaneous transluminal coronary angioplasty in 2013. The same year, he was admitted to the Hypertension Unit of the University of Pisa for uncontrolled hypertension (office BP, 240/150 mm Hg and day-time ambulatory BP monitoring 200/102 mm Hg). Secondary causes of hypertension were ruled out. After several drug changes, the patient was treated with furosemide 50 mg/d, metoprolol 100 mg/d, spironolactone 50 mg/d, ramipril 10 mg/d, and amlodipine 10 mg/d without BP control. In March 2014, he underwent radiofrequency renal denervation without complications, but no significant BP reduction. Seven months …

Background:Vitamin D deficiency is related to an increased prevalence of cardiovascular disease. Renin-angiotensin-aldosterone system suppression and vascular dysfunction are considered among the main mechanisms implicated in this association. However, interventional studies demonstrating that vitamin D replacement reduces circulating renin-angiotensin-aldosterone components and improves vascular function in humans are still lacking.Methods:Thirty-three consecutive patients with essential hypertension and hypovitaminosis D underwent therapy with cholecalciferol 50000IU/week orally for 8 weeks. Thirty-three hypertensive patients with normal vitamin D levels and 20 normotensive individuals were also enrolled as control groups. At baseline and at the end of the study, we evaluated plasma renin activity, circulating renin, angiotensin II, aldosterone and plasma vitamin D levels. Endothelial function [flow-mediated dilation (FMD)], carotid-femoral pulse wave velocity and augmentation index, peripheral and central blood pressure were also acquired.Results:After 8-week cholecalciferol administration, all treated patients normalized plasma 25(OH)D values. Furthermore, a reduction in plasma levels of plasma renin activity (1.170.3 vs 1.51 +/- 0.4ng/ml per h, P=0.02), renin (13.4 +/- 1.7 vs 19.2 +/- 2.9pg/ml, P<0.001), angiotensin II (11.6 +/- 1.6 vs 15.8 +/- 2.7pg/ml, P=0.02) was observed at the end of the study. FMD was significantly increased after cholecalciferol treatment (4.4 +/- 2.6 vs 3.3 +/- 2.1%, P<0.05), in the absence of changes of brachial artery diameter and endothelium-independent vasodilation. Carotid-femoral pulse wave velocity and augmentation index were not modified, as well peripheral and central blood pressure.Conclusion:The restoration of normal vitamin D levels after 8-week cholecalciferol treatment is able to inhibit peripheral renin-angiotensin system and improve FMD in essential hypertensive patients with hypovitaminosis D.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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.

Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein–activated inward rectifier K + channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3 , encoding Na + /K + -ATPase 1 and Ca 2+ -ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1 , ATP2B3 , and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na + /K + -ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without these or KCNJ5 mutations. Overexpression of Na + /K + -ATPase p.Gly99Arg and GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene expression and its transcriptional regulator NR4A2. Structural modeling of the Na + /K + -ATPase showed that the Gly99Arg substitution most likely interferes with the gateway to the ion binding pocket. In vitro functional assays demonstrated that Gly99Arg displays severely impaired ATPase activity, a reduced apparent affinity for Na + activation of phosphorylation and K + inhibition of phosphorylation that indicate decreased Na + and K + binding, respectively. Moreover, whole cell patch-clamp studies established that overexpression of Na + /K + -ATPase Gly99Arg causes membrane voltage depolarization. In conclusion, somatic mutations are common in APAs that result in an increase in CYP11B2 gene expression and may account for the dysregulated aldosterone production in a subset of patients with sporadic primary aldosteronism.

INTRODUCTION:The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population.METHODS:A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake.RESULTS:The average sodium intake was 172  mmol (or 10.1  g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5  g/day. The average potassium intake was 63 and 56  mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100  mmol/day or 3.9  g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P <0.001). There was also a direct association between BMI and sodium intake in both sexes, this association being independent of age (P < 0.001).CONCLUSION:In this national sample of the Italian hypertensive population, dietary sodium intake was largely higher and potassium intake much lower than the recommended intakes, and this was true for all geographical areas. Overweight and obese hypertensive patients had particularly high sodium intakes.

BACKGROUND Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. AIM The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. MATERIALS & METHODS We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. RESULTS We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10(-8)). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. CONCLUSION Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension.

Introduction: The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population. Methods: A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake. Results: The average sodium intake was 172 mmol (or 10.1 g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5 g/day. The average potassium intake was 63 and 56 mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100 mmol/day or 3.9 g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P <0.001). There was also a direct association between BMI and sodium intake in both sexes, this association being independent of age (P < 0.001). Conclusion: In this national sample of the Italian hypertensive population, dietary sodium intake was largely higher and potassium intake much lower than the recommended intakes, and this was true for all geographical areas. Overweight and obese hypertensive patients had particularly high sodium intakes.

Riassunto L’edema ciclico idiopatico è una sindrome non infiammatoria caratterizzata da un obiettivo incremento ponderale o dalla percezione soggettiva di aumento del peso corporeo per cause non precisate. La sindrome colpisce pressoché esclusivamente il sesso femminile nella vita riproduttiva, e si caratterizza per la sensazione di tensione generalizzata e ritenzione idrica in posizione ortostatica. L’escursione ponderale giornaliera è variabile, ma può raggiungere anche svariati chilogrammi. Poco si sa sulla genesi della malattia, anche se, verosimilmente, numerosi fattori possono concorrere in varia misura, come una attivazione del sistema renina-angiotensina, disturbi ipotalamici, alterazioni dopaminergiche sistemiche o renali e alterazioni anatomiche della parete vascolare con aumento della permeabilità capillare. Non raramente la malattia si instaura in pazienti con disturbi della condotta alimentare o comunque con alterazione del tono dell’umore e spesso è aggravata dall’uso di farmaci (diuretici, lassativi) che, assunti con lo scopo di perdere peso, aggravano poi la sintomatologia iniziale. La diagnosi di edema idiopatico è da porre dopo avere escluso tutte le altre forme note di edema localizzato o generalizzato. I provvedimenti terapeutici sono concentrati sul controllo del peso corporeo tramite una dieta povera di sodio, limitata nei carboidrati e generosa nei liquidi, il mantenimento giornaliero di posizione clinostatica alternat o a lunghe camminate e talora l’elastocompressione degli arti inferiori. Dal punto di vista farmacologico, è stato proposto l’uso di ACE-inibitori o antialdosteronici, senza peraltro durevoli successi, mentre i diuretici dell’ansa, i farmaci dopaminergici e soprattutto le amine simpaticomimetiche sembrano del tutto inutili e talora ricchi di effetti collaterali.