Application of enhanced recovery after surgery (ERAS) protocols in adrenal surgery: A retrospective, preliminary analysis.

BACKGROUND: The present study was conducted to evaluate the impact of enhanced recovery after surgery (ERAS) pathway in patients undergoing laparoscopic adrenalectomy (LA) for primary and secondary adrenal disease, in reducing the length of primary hospital stay and return to daily activities. MATERIALS AND METHODS: This retrospective study was carried out on 61 patients who underwent LA. A total of 32 patients formed the ERAS group. A total of 29 patients received conventional perioperative care and were assigned as the control group. Groups were compared in terms of patient's characteristics (sex, age, pre-operative diagnosis, side of tumour, tumour size and co-morbidities), post-operative compliance (anaesthesia time, operative time, post-operative stay, post-operative numeric rating scale (NRS) score, analgesic assumption and days to return to daily activities) and post-operative complications. RESULTS: No significant differences in anaesthesia time ( P = 0.4) and operative time ( P = 0.6) were reported. NRS score 24 h postoperatively was significantly lower in the ERAS group ( P < 0.05). The analgesic assumption in post-operative period in the ERAS group was lower ( P < 0.05). ERAS protocol led to a significantly shorter length of post-operative stay ( P < 0.05) and to return to daily activities ( P < 0.05). No differences in peri-operative complications were reported. DISCUSSION: ERAS protocols seem safe and feasible, potentially improving perioperative outcomes of patients undergoing LA, mainly improving pain control, hospital stay and return to daily activities. Further studies are needed to investigate overall compliance with ERAS protocols and their impact on clinical outcomes.

Assessment of sST2 Behaviors to Evaluate Severity/Clinical Impact of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is a potentially life-threatening disorder. Beyond its usefulness in the prognostic stratification of heart failure, sST2 can represent a biomarker with high utility in several acute conditions. Our study was aimed to investigate whether sST2 can be used as a clinical marker of severity and prognostic outcome in acute PE. We enrolled 72 patients with documented PE and 38 healthy subjects; we measured the plasma concentrations of sST2 to evaluate the prognostic and severity performance of different levels of sST2 according to its association with the pulmonary embolism severity index (PESI) score and several parameters of respiratory function. PE patients had significantly higher levels of sST2 compared with healthy subjects (87.74 ± 17.1 vs. 17.1 ± 0.4 ng/mL, p < 0.001); we found higher PESI scores and serum lactate values in the group of patients with sST2 > 35 ng/mL compared with patients with sST2 < 35 ng/mL (138.7 ± 14.9 vs. 103.7 ± 15.1 and 2.43 ± 0.69 vs. 1.025 ± 0.05 mmol/L, respectively; p < 0.05). Patients with sST2 > 35 ng/mL showed higher radiological severity of PE compared with patients with sST2 < 35 ng/mL. Moreover, sST2 was the strongest parameter with a discriminative capacity for the development of acute respiratory failure and a PESI score >106 with respect to C reactive protein (CRP), creatinine, d-dimer, and serum lactate. We clearly demonstrated that sST2 significantly increased in PE and that its elevation was associated with disease severity. Therefore, sST2 may be used as a clinical marker in the evaluation of PE severity. However, further studies with larger patient populations are required to confirm these findings.

Laparoscopic-Guided Ropivacaine Trocar-Site Infiltration Can Improve Post-Operative Pain Control after Laparoscopic Adrenalectomy.

BACKGROUND: There is no consensus on pain control in patients undergoing laparoscopy; nowadays, conventional therapy may be improved by transversus abdominis plane block. The aim of this evaluation is to investigate the role of laparoscopic-assisted trocar-site ropivacaine infiltration during adrenalectomy in pain control. METHODS: This is a retrospective evaluation of a prospectively maintained database including patients undergoing adrenalectomy. Patients were divided into 2 groups: Group A patients received laparoscopic-assisted trocar-site infiltration of 7.5 mg/mL ropivacaine and Group B patients did not receive any infiltration. All patients received a 24-hour infusion of 20 mg morphine; pain was checked at 6, 24, and 48 hours after surgery by Visual Analogue Scale (VAS) score. A rescue analgesia by was given if VAS score was > 4 or on patient request. RESULTS: No differences in operative time, complications, and post-operative stay and no complications related to trocar-site infiltration were found. 6-hour and 48-hour VAS scores were not found to be significantly different between groups, even if a slight decrease in VAS score in Group A was reported. Group A showed significant reduction in VAS score at 24 hours (2.44 +/- .41 vs 3.01 +/- .78, P < .005) and in the number of patients requiring further analgesic drugs administration (40.6% vs 57.8%, P < .005). CONCLUSIONS: Laparoscopic-guided trocar-site ropivacaine infiltration can be considered safe and effective in the management of post-operative pain and in the reduction of analgesic need in patients undergoing laparoscopic adrenalectomy. The retrospective nature of the study and the lack of a consistent series of patients require further evaluations.

Prognostic Role of sST2 in Acute Heart Failure and COVID-19 Infection-A Narrative Review on Pathophysiology and Clinical Prospective.

The importance of cardiovascular biomarkers in clinical practice increased dramatically in the last years, and the interest extends from the diagnosis purpose to prognostic applications and response to specific treatment. Acute heart failure, ischemic heart failure, and COVID-19 infection represent different clinical settings that are challenging in terms of the proper prognostic establishment. The aim of the present review is to establish the useful role of sST2, the soluble form of the interleukin-1 receptor superfamily (ST2), physiologically involved in the signaling of interleukin-33 (IL-33)-ST2 axis, in the clinical setting of acute heart failure (HF), ischemic heart disease, and SARS-CoV-2 acute infection. Molecular mechanisms associated with the IL33/ST2 signaling pathways are discussed in view of the clinical usefulness of biomarkers to early diagnosis, evaluation therapy to response, and prediction of adverse outcomes in cardiovascular diseases.

Time to hospitalisation, CT pulmonary involvement and in-hospital death in COVID-19 patients in an Emergency Medicine Unit.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) are often treated at home given the limited healthcare resources. Many patients may have sudden clinical worsening and may be already compromised at hospitalisation. We investigated the burden of lung involvement according to the time to hospitalisation. METHODS: In this observational cohort study, 55 consecutive COVID-19-related pneumonia patients were admitted to the Emergency Medicine Unit. Groups of lung involvement at computed tomography were classified as follows: 0 (<5%), 1 (5%-25%), 2 (26%-50%), 3 (51%-75%) and 4 (>75%). We also investigated in-hospital death and the predictive value of Yan-XGBoost model and PREDI-CO scores for death. RESULTS: The median age was 74 years and 34 were men. Time to admission increased from 2 days in group 0 to 8.5-9 days in groups 3 and 4. A progressive increase in LDH, CRP and d-dimer was found across groups, while a decrease of lymphocytes paO2 /FiO2 ratio and SpO2 was found. Ten (18.2%) patients died during the in-hospital staying. Patients who died were older, with a trend to lower lymphocytes, a higher d-dimer, creatine phosphokinase and troponin T. The Yan-XGBoost model did not accurately predict in-hospital death with an AUC of 0.57 (95% confidence interval [CI] 0.37-0.76), which improved after the addition of the lung involvement groups (AUC 0.68, 95%CI 0.45-0.90). Conversely, a good predictive value was found for the original PREDI-CO score with an AUC of 0.76 (95% CI 0.58-0.93) which remained similar after the addition of the lung involvement (AUC 0.76, 95% CI 0.57-0.94). CONCLUSION: We found that delayed hospital admission is associated with higher lung involvement. Hence, our data suggest that patients at risk for more severe disease, such as those with high LDH, CRP and d-dimer, should be promptly referred to hospital care.

Cardiomyopathies and Adrenal Diseases.

Cardiomyopathies are myocardial disorders in which heart muscle is structurally and/or functionally abnormal. Previously, structural cardiomyocyte disorders due to adrenal diseases, such as hyperaldosteronism, hypercortisolism, and hypercatecholaminism, were misunderstood, and endomyocardial biopsy (EMB) was not performed because was considered dangerous and too invasive. Recent data confirm that, if performed in experienced centers, EMB is a safe technique and gives precious information about physiopathological processes implied in clinical abnormalities in patients with different systemic disturbances. In this review, we illustrate the most important features in patients affected by primary aldosteronism (PA), Cushing's syndrome (CS), and pheochromocytoma (PHEO). Then, we critically describe microscopic and ultrastructural aspects that have emerged from the newest EMB studies. In PA, the autonomous hypersecretion of aldosterone induces the alteration of ion and water homeostasis, intracellular vacuolization, and swelling; interstitial oedema could be a peculiar feature of myocardial toxicity. In CS, cardiomyocyte hypertrophy and myofibrillolysis could be related to higher expression of atrogin-1. Finally, in PHEO, the hypercontraction of myofilaments with the formation of contraction bands and occasional cellular necrosis has been observed. We expect to clear the role of EMB in patients with cardiomyopathies and adrenal disease, and we believe EMB is a valid tool to implement new management and therapies.

A sleep apnoea questionnaire predicts organ damage in hypertensive patients.

BACKGROUND: Arterial hypertension is associated with obstructive sleep apnoea, poor quality and duration of sleep, which might contribute to hypertension-mediated organ damage. METHODS: We investigated the presence of insomnia, restless legs syndrome, and obstructive sleep apnoea using validated questionnaires (Insomnia Severity Index, Restless Legs Syndrome Rating Scale, and STOP-Bang), and their relationship with hypertension-mediated organ damage, in hypertensive patients. RESULTS: In 159 consecutive consenting hypertensive patients [age 47(11) years, median and (interquartile range), body mass index 25.5(5.9) kg/m2, office systolic and diastolic blood pressure 144(23)/92(12) mmHg], the STOP-Bang, but not the other scores, predicted cardiac remodelling: compared to patients with a STOP-Bang score < 3, those at high risk of obstructive sleep apnoea showed higher left ventricular mass index [49.8(11.9) vs. 43.3(11.9) g/m2.7, p < 0.0001], left atrium volume [25.7(2.5) vs. 25.0(2.8) ml/m2, p = 0.003], and aortic root diameter [33.6(3.0) vs. 33.0(3.7) mm, p < 0.0001]. They did not differ for microalbuminuria and estimated glomerular filtration rate. At multivariate analysis, after adjustment for office systolic blood pressure values, the STOP-Bang score remained a predictor of left ventricular mass index; while the Insomnia Severity Index and restless legs syndrome risk score had no predictive value. However, a significant interaction between STOP-Bang and Restless Legs Syndrome Rating Scale scores in determining left ventricular remodelling was found. CONCLUSIONS: In consecutive hypertensive stage I patients the STOP-Bang questionnaire allowed identification of a high-risk cohort featuring a more prominent cardiac damage. Hence, this inexpensive tool can be useful for risk stratification purposes in municipalities with limited access to health care resources.

Magnetic resonance imaging 3T and total fibrotic volume in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. AIM: To identify and quantify ADPKD, through a novel magnetic resonance imaging protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the renal function. METHODS: A total of 15 ADPKD patients had undergone renal testing on MRI 3Tesla at T0 and were revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima-media thickness, ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS: Our study showed a significant negative correlation between total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) during observation (P < 0.02). We showed a negative correlation between eGFR with total fibrotic volume (TFV) (P < 0.04) and total perfusion volume/TKV (P < 0.02). Moreover TFV was correlated positively with PAC (P < 0.05), insulin values (P < 0.05), ABI (P < 0.05) and LVMI (P < 0.01). CONCLUSION: The MRI 3Tesla, despite the high costs, could be considered as a useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger groups are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies.

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.

Clinical impact of transient lymphopenia.

Transient or persistent immunosuppression is a known risk factor for morbidity and mortality in critically ill patients. Aim of the present study is to evaluate the lymphopenia in patients admitted to the Emergency Unit of AOU Policlinico Umberto I, to investigate its prevalence at admission and the persistence during hospitalization until discharge. Possible correlations were evaluated between lymphopenia, diagnosis of admission, comorbidities and chronic treatments. In this study, 240 patients (142 men; 98 female; mean age 75.1 ± 15.1) were enrolled. Patients were divided into two groups according to the lymphocytes count at hospital admission, namely "Group A" with lymphopenia and "Group B" with values in the normal range. Moreover, the patients in group A were distinguished in relation to the regression or persistence of the lymphopenia assessed at the time of hospital discharge (Group A1: persistence; Group A2: normalization). Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; and none differences were observed regarding gender. Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; no differences were observed regarding gender. All subsets of the lymphocytes (CD4+, CD8+, NK) were equally reduced. Persistent lymphopenia was found in 19% of patients. Lymphopenia should be valued at the time of hospital admission as a factor influencing the prognosis, the management and the treatment of these patients.

Relevance of obesity-related organ damage and metabolic syndrome classification in cardiovascular and renal risk stratification in patients with essential hypertension.

Introduction: Hypertension is a relevant cardiovascular comorbidity. Adipose tissue represents a metabolically active tissue involved in the regulation of blood pressure and metabolic alterations. In recent decades, several classifications for the metabolic syndrome (MS) have been proposed. Recently, a new syndrome called the "Cardiovascular-kidney-metabolic" (CKM) syndrome was identified, to determine patients at high cardiovascular and metabolic risk. The aim of the study was to compare different classifications in a large population of hypertensive patients. Materials and methods: Between September 2022 and August 2023, we consecutively enrolled 772 hypertensive patients (407 men; 365 women; mean age 52.2 ± 15.1 years), evaluating anthropometric, biochemical, and instrumental parameters (transthoracic echocardiogram, carotid echo-Doppler, 24-h ambulatory blood pressure monitoring, fundus oculi). Results: Using different classifications we found MS prevalence: Adult Treatment Panel III (ATP-III) 28.8%, International Diabetes Federation (IDF) 31.5%, CKM 40.7%. CKM Classes 3 and 4 showed higher body mass index and waist circumference compared with other groups. Compared with ATP-III and IDF, CKM Class 4 showed higher 24-h systolic blood pressure, lower percentage of controlled hypertension, increased interventricular septum and posterior wall, reduced ejection fraction, and greater prevalence of hypertensive arterial retinal damage. Discussion: Visceral obesity and MS are frequent conditions with healthy impact, becoming an important trigger for the development of cardiovascular and metabolic complications. The different MS classifications allow the early identification of patients at high risk of cardiometabolic complications. The new CKM syndrome proves useful to identify individuals at high risk for CKM morbidity and mortality.

Ultrasound-guided Transversus Abdominis Plane Block is Effective as Laparoscopic Trocar site infiltration in Postoperative Pain Management in Patients Undergoing Adrenal Surgery.

BACKGROUND: Pain management in patients undergoing laparoscopy is still a matter of debate as several techniques have been proposed to reduce postoperative analgesic consumption and improve recovery. Among these, transversus abdominis plane (TAP) block is considered as safe, effective, and easy to perform under ultrasound guidance; even so, recently laparoscopically guided trocar site anesthetic infiltration has been proposed as a "surgeon-dependent alternative to TAP block." The aim of this evaluation is to compare these analgesic techniques in the setting of laparoscopic adrenalectomy. METHODS: This is a retrospective evaluation of a prospectively maintained database. Patients were divided into two groups: Group A patients received laparoscopic-assisted trocar site infiltration of ropivacaine; Group B patients received bilateral ultrasound-guided TAP block with ropivacaine. All patients received 24 h infusion of 20 mg morphine postoperatively; pain was checked at 6, 24 and 48 h after surgery. A rescue analgesia was given if numerical rating scale (NRS) score was > 4 or on patient request. RESULTS: One hundred and three patients were enrolled in the evaluation (57 in group A and 46 in group B). There were no differences in operative time, complications and postoperative stay, and no complications related to trocar site infiltration. There were no differences in NRS at 6, 24, and 48 hours as well as in patients requiring further analgesic administration. CONCLUSIONS: Laparoscopic-guided trocar site ropivacaine infiltration has similar pain outcomes compared to ultrasound-guided TAP block in the management of postoperative pain in patients undergoing laparoscopic adrenalectomy. Since there is no difference among these techniques, the decision can be based on surgeon or anesthesiologist preference.

Pulmonary embolism post-Covid-19 infection: physiopathological mechanisms and vascular damage biomarkers.

Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2).

Association between subclinical atherosclerosis and oral inflammation: A cross-sectional study.

BACKGROUND: The aim of this cross-sectional study was to investigate the association between carotid intima-media thickness (c-IMT) values and periodontal and peri-implant diseases in a sample of patients with hypertension. METHODS: A total of 151 participants with presence of at least one dental implant in function for >5 years were recruited. Anthropometric measurements, 24-h ambulatory blood pressure monitoring, ultrasound assessment of carotid arteries (c-IMT and presence of plaque) were recorded and venous blood samples obtained. An oral examination was performed by calibrated examiners to ascertain prevalence and severity of periodontal and peri-implant diseases. Binomial logistic regression was performed to investigate the potential association between various measures of exposure of dental diseases and predictors of cardiovascular risk (c-IMT > 0.9 mm and presence of plaque or their combination). RESULTS: Diagnosis of periodontitis (OR 6.71, 95% CI: 2.68-16.76, P < 0.001), cumulative mucosal/gingival inflammation (Periodontal Screening and Recording score) (OR 1.25, 95% CI:1.12-1.41, P < 0.001), and mucositis (OR 3.34, 95% CI:1.13-9.85, P < 0.05) were associated with c-IMT > 0.9 mm and/or plaque presence independent of age, sex, smoking, 24 h systolic blood pressure and body mass index differences. No statistically significant results were noted for peri-implantitis. Linear regression models confirmed a positive association of cumulative mucosal/gingival inflammation (ß = 0.011, SE 0.002, P < 0.001), diagnosis of periodontitis (ß = 0.114, SE 0.020, P < 0.001), and peri-implant diseases (ß = 0.011, SE 0.002, P < 0.001) with increased c-IMT values. CONCLUSIONS: This study confirms a positive association between mucosal/gingival inflammation and subclinical atherosclerosis assessed by c-IMT values and the presence of carotid plaque in patients with hypertension, independent of traditional cardiovascular risk factors. Future studies are needed to further characterize this relationship.

Natural Activators of Autophagy Reduce Oxidative Stress and Muscle Injury Biomarkers in Endurance Athletes: A Pilot Study.

BACKGROUND: Oxidative stress and impaired autophagy are directly and indirectly implicated in exercise-mediated muscle injury. Trehalose, spermidine, nicotinamide, and polyphenols possess pro-autophagic and antioxidant properties, and could therefore reduce exercise-induced damage to skeletal muscle. The aim of this study was to investigate whether a mixture of these compounds was able to improve muscle injury biomarkers in endurance athletes through the modulation of oxidative stress and autophagic machinery. METHODS AND RESULTS: sNOX2-dp; H2O2 production; H2O2 breakdown activity (HBA); ATG5 and p62 levels, both markers of autophagic process; and muscle injury biomarkers were evaluated in five endurance athletes who were allocated in a crossover design study to daily administration of 10.5 g of an experimental mixture or no treatment, with evaluations conducted at baseline and after 30 days of mixture consumption. Compared to baseline, the mixture intake led to a remarkable reduction of oxidative stress and positively modulated autophagy. Finally, after the 30-day supplementation period, a significant decrease in muscle injury biomarkers was found. CONCLUSION: Supplementation with this mixture positively affected redox state and autophagy and improved muscle injury biomarkers in athletes, allowing for better muscle recovery. Moreover, it is speculated that this mixture could also benefit patients suffering from muscle injuries, such as cancer or cardiovascular patients, or elderly subjects.

Evaluation of Intra-Renal Stiffness in Patients with Primary Aldosteronism.

INTORDUCTION: Aldosterone is known to play important role in developing cardiovascular, metabolic, renal damage in hypertensive patients. AIM: Aim of study was to evaluate parameters obtained by eco-color Doppler study, as non-invasive and easly performed method in asyntomatic patients with Essential Hypertension (EH) and Primary Aldosteronism (PA), without overt organ damage. METHODS: From April 2019 to March 2020 we consecutively enrolled 73 hypertensive subjects (48 males, 25 women), distinguished in two groups: 30 EH patients (mean age 49.5 ± 18.7 years) and 43 PA patients (mean age 53.1 ± 11.6 years)] [23 with aldosterone-secreting adrenal adenoma (APA), 20 with idiopathic aldosteronism (IHA)]. RESULTS: PA group showed higher renal filtration rate and 24-h urinary excretion of albumin respect to EH; moreover, in PA we found higher Pulsatility Index, altered percentage of Renale Resistance Index, Atrophy Index, and reducted parietal thickness than EH. The correlation study showed that plasma aldosterone were positively correlated with pulsatility index in PA group (right r = 0.35; p < 0.05; left r = 0.36; p < 0.05). CONCLUSION: parameters obtained through the intra-renal eco-color Doppler examination, easly performed and non-invasive, can be useful in the early-stage identification of subclinical microvascular alterations, especially in PA, condition characterized by increased risk of cardio-vascular remodelling and metabolic alterations.

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.

Background: Primary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA). Methods: The quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA). Results: Real-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA. Conclusion: This study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA.

The metabolic phenotype of patients with primary aldosteronism: impact of subtype and sex - a multicenter-study of 3566 Caucasian and Asian subjects.

Background: Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics. Methods: We conducted a retrospective multicenter study including 3566 patients with APA or IHA of Caucasian and Asian origin. We compared the prevalence of metabolic disorders between APA and IHA patients at the time of diagnosis and 1-year post-intervention, with special references to sex differences. Furthermore, correlations between metabolic parameters and plasma aldosterone, renin, or plasma cortisol levels after 1 mg dexamethasone (DST) were performed. Results: As expected, APA patients were characterized by higher plasma aldosterone and lower serum potassium levels. Only female IHA patients demonstrated significantly worse metabolic parameters than age-matched female APA patients, which were associated with lower cortisol levels upon DST. One-year post-intervention, female adrenalectomized patients showed deterioration of their lipid profile, when compared to patients treated with mineralocorticoid receptor antagonists. Plasma aldosterone levels negatively correlated with the BMI only in APA patients. Conclusions: Metabolic alterations appear more prominent in women with IHA. Although IHA patients have worse metabolic profiles, a correlation with cortisol autonomy is documented only in APAs, suggesting an uncoupling of cortisol action from metabolic traits in IHA patients.

Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.

BACKGROUND: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). METHODS: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. FINDINGS: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). INTERPRETATION: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. FUNDING: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino.

[Adrenal pheochromocytoma associated with "tako-tsubo" syndrome]. / Un caso di feocromocitoma surrenalico manifestatosi con un quadro di cardiomiopatia tipo "tako-tsubo".

"Tako-tsubo" cardiomyopathy is a condition characterized by a transitory left ventricular asinergia, induced by physical and emotional stress. In literature there are few cases of association between cardiomyopathy and pheochromocytoma. We described a case of a 72 year-old woman admitted in Emergency Room for chest pain associated with high blood pressure: the ECG showed non-ST elevation in leads III, AVF and V1. An echocardiogram showed global reduction in contractility (EF 40%) with apical akinesia. The coronary angiography showed coronary without stenosis while left ventriculography showed an average apical akinesia of the anterior wall with enhanced contractility of basal segments. Subsequently, the patient continued to present episodes of tremors associated with high blood pressure and therefore was made the determination of urinary metanephrines and urinary vanilmandelic acid that were both high. A subsequent abdomen MRI showed a 32 mm left adrenal lesion with arterial phase impregnation. The diagnosis of left adrenal pheochromocytoma was made and the tumor, after appropriate preoperative pharmacological preparation with α-blockers, was removed surgically. In conclusion, the unexplained transitory left ventricular asinergia alert the clinician of an underlying disorder, such as pheochromocytoma, the early detection of which is crucial to the prognosis.