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The cardiometabolic implications of Non-Functioning Adrenal Incidentaloma (NFAI) is still matter of debate. This study takes a novel approach to analyze this association, accounting for the influence of various confounding factors. We present the findings of a retrospective, cross-sectional, and case-control study. Data from all NFAI patients in primary prevention, referred to the University of Turin between 2000 and 2023, were collected and compared with subjects without adrenal disease, using propensity score matching analysis. A total of 1997 patients were included (906 patients with NFAI; 1091 controls). Adrenal tumor group was associated with high levels of cardiovascular risk scores in both univariate and multiple linear regression analyses (Progetto CUORE: EC 11.00, 95% CI 2.72-44.46, p = 0.001; SCORE: EC 1.97, 95% CI 1.01-3.81, p = 0.046). Regarding cardiometabolic complications, multivariable logistic regression revealed an independent association between NFAI and ascending aorta dilation (OR 4.64, 95% CI 2.24-9.63, p = 0.000), after adjusting for age, sex, smoking status, metabolic syndrome, number of antihypertensive drugs, estimated glomerular filtration rate (eGFR), and normetanephrine levels. Propensity score matching analysis (1:1 matching ratio), based on the same logistic regression model, confirmed the association of NFAI with aortic dilation (ß = 0.083, 95% CI 0.008-0.157, p = 0.030). No significant associations were found with metabolic syndrome, type II diabetes, eGFR <60 mL/min/1.73 m2, microalbuminuria, atrial fibrillation, or hypertensive heart disease. This study suggests that patients with NFAI face increased cardiometabolic risk and high prevalence of ascending aorta dilation. Routine evaluation of NFAI patients should include thorough cardiovascular assessment and consideration of treatments aimed at reducing cardiovascular risk.
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Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.
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PURPOSE: In this retrospective, observational study we aim to compare the outcomes of the RFA treatment of benign thyroid nodules, carried out respectively with the standard fixed-needle approach (FTN) and the adjustable-tip needle technique (ATN), considered a more tailored, quicker and easier technical approach. METHODS: We enrolled 36 patients who underwent RFA treatment of symptomatic, benign, thyroid nodule, 18 with the ATN and 18 with the FTN approach, respectively. Data about absolute volume reduction, volume reduction rate (VRR) and success rate (defined as VRR ≥ 50%), after 1, 3 and 6 months of follow-up were compared. RESULTS: Our study suggested no substantial difference between the approaches, up to 6 months of follow-up, both in terms of absolute reduction (p = 0.27) and VRR (p = 0.14). These results were confirmed when the success rates, both in terms of 50%-reduction (p = 0.12) and absolute reduction (p = 0.42), was considered. Only at the 6-month evaluation, the FTN procedure showed a better success rate, yet without statistical significance (88.9% vs. 61.1%, p = 0.12). No difference emerged both in terms of patients' satisfaction and safety. CONCLUSION: Our small experience suggested no substantial difference between ATN and FTN, in terms of outcomes. On the other hand, ATN was considered to be more straightforward and could consequently allow for a shorter operator learning curve.
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Agulhas , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Estudos Retrospectivos , Feminino , Nódulo da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/instrumentação , Adulto , Resultado do Tratamento , Itália , Idoso , Desenho de Equipamento , SeguimentosRESUMO
Brugada syndrome (BrS) is an inherited disorder that can cause ventricular fibrillation and sudden cardiac death in individuals with otherwise structurally normal hearts. Several provoking factors are known to potentially unmask or exacerbate a typical Brugada ECG pattern in predisposed subjects. Hypothyroidism has been suggested as one of these triggers, but the exact mechanisms underlying this relationship remain poorly understood. Moreover, the severity of thyroid dysfunction beyond which a Brugada-type ECG alteration might be triggered is still unclear. We report the case of a 33-year-old male who displayed a Brugada type 1 ECG pattern and was diagnosed with severe hypothyroidism (TSH > 100 mU/L with undetectable levels of fT4 and fT3). Hormonal replacement therapy with levothyroxine was initiated at increasing doses; serial biochemical and ECG controls were performed, initially every 3 weeks up to 15 weeks and afterward every 3 months. The regression of typical Brugada ECG waveforms could be seen at an early stage, when the patient was still taking a low dose of levothyroxine (37.5 µg/day, i.e., one-fourth of his final requirements of 150 µg/day), and laboratory tests still showed a marked alteration of thyroid hormonal parameters. Hypothyroidism may act as a trigger for Brugada-type ECG abnormalities, but a very severe alteration of the hormonal parameters is necessary to prompt these alterations. In our case, the initiation of replacement therapy with levothyroxine rapidly reversed the ECG modifications, even at a low subtherapeutic dose.
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Síndrome de Brugada , Hipotireoidismo , Doenças da Glândula Tireoide , Adulto , Humanos , Masculino , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/etiologia , Eletrocardiografia , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Doenças da Glândula Tireoide/complicações , Tiroxina/uso terapêuticoRESUMO
SUMMARY Brugada syndrome (BrS) is an inherited disorder that can cause ventricular fibrillation and sudden cardiac death in individuals with otherwise structurally normal hearts. Several provoking factors are known to potentially unmask or exacerbate a typical Brugada ECG pattern in predisposed subjects. Hypothyroidism has been suggested as one of these triggers, but the exact mechanisms underlying this relationship remain poorly understood. Moreover, the severity of thyroid dysfunction beyond which a Brugada-type ECG alteration might be triggered is still unclear. We report the case of a 33-year-old male who displayed a Brugada type 1 ECG pattern and was diagnosed with severe hypothyroidism (TSH > 100 mU/L with undetectable levels of fT4 and fT3). Hormonal replacement therapy with levothyroxine was initiated at increasing doses; serial biochemical and ECG controls were performed, initially every 3 weeks up to 15 weeks and afterward every 3 months. The regression of typical Brugada ECG waveforms could be seen at an early stage, when the patient was still taking a low dose of levothyroxine (37.5 µg/day, i.e., one-fourth of his final requirements of 150 µg/day), and laboratory tests still showed a marked alteration of thyroid hormonal parameters. Hypothyroidism may act as a trigger for Brugada-type ECG abnormalities, but a very severe alteration of the hormonal parameters is necessary to prompt these alterations. In our case, the initiation of replacement therapy with levothyroxine rapidly reversed the ECG modifications, even at a low subtherapeutic dose.
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Background: The systematic use of confirmatory tests in the diagnosis of primary aldosteronism (PA) increases costs, risks and complexity to the diagnostic work-up. In light of this, some authors proposed aldosterone-to-renin (ARR) cut-offs and/or integrated flow-charts to avoid this step. Patients with resistant hypertension (RH), however, are characterized by a dysregulated renin-angiotensin-aldosterone system, even in the absence of PA. Thus, it is unclear whether these strategies might be applied with the same diagnostic reliability in the setting of RH. Methods: We enrolled 129 consecutive patients diagnosed with RH and no other causes of secondary hypertension. All patients underwent full biochemical assessment for PA, encompassing both basal measurements and a saline infusion test. Results: 34/129 patients (26.4%) were diagnosed with PA. ARR alone provided a moderate-to-high accuracy in predicting the diagnosis of PA (AUC=0.908). Among normokalemic patients, the ARR value that maximized the diagnostic accuracy, as identified by the Youden index, was equal to 41.8 (ng/dL)/(ng/mL/h), and was characterized by a sensitivity and a specificity of 100% and 67%, respectively (AUC=0.882); an ARR > 179.6 (ng/dL)/(ng/mL/h) provided a 100% specificity for the diagnosis of PA, but was associated with a very low sensitivity of 20%. Among hypokalemic patients, the ARR value that maximized the diagnostic accuracy, as identified by the Youden index, was equal to 49.2 (ng/dL)/(ng/mL/h), and was characterized by a sensitivity and a specificity of 100% and 83%, respectively (AUC=0.941); an ARR > 104.0 (ng/dL)/(ng/mL/h) provided a 100% specificity for the diagnosis of PA, with a sensitivity of 64%. Conclusions: Among normokalemic patients, there was a wide overlap in ARR values between those with PA and those with essential RH; the possibility to skip a confirmatory test should thus be considered with caution in this setting. A better discriminating ability could be seen in the presence of hypokalemia; in this case, ARR alone may be sufficient to skip confirmatory tests in a suitable percentage of patients.
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Hiperaldosteronismo , Hipertensão , Hipopotassemia , Humanos , Aldosterona , Renina , Reprodutibilidade dos Testes , Hipertensão/complicações , Hipertensão/diagnóstico , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnósticoRESUMO
Introduction: In type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount. Aim: To investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients. Methods: The GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90. Results: Among endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p < 0.001), while copeptin did not. Conclusion: In patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient's baseline volume conditions. Clinical trial registration: Clinicaltrials.gov, identifier NCT03917758.
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Glycemic alterations are frequent in patients with pheochromocytoma and paraganglioma (PPGL), but the real incidence of secondary diabetes mellitus (DM) is uncertain, because prospective multicenter studies on this topic are lacking in the literature. The main pathophysiological mechanisms of glucose homeostasis alterations in PPGL, related to catecholamine hypersecretion, are impaired insulin and glucagon-like peptide type 1 (GLP-1) secretion and increased insulin resistance. Moreover, it has been reported that different pathways leading to glucose intolerance may be related to the secretory phenotype of the chromaffin tumor. Predictive factors for the development of glucose intolerance in PPGL patients are a higher age at diagnosis, the need for a higher number of anti-hypertensive drugs, and the presence of secreting neoplasms. Tumor resection is strongly related to the resolution of DM in PPGL patients, with a significant improvement of glycemic control in most cases. We can hypothesize a different personalized therapeutic approach based on the secretory phenotype. The adrenergic phenotype is more closely related to reduced insulin secretion, so insulin therapy may be required. On the other hand, the noradrenergic phenotype mainly acts by increasing insulin resistance and, therefore, insulin-sensitizing antidiabetic agents can find a greater application. Regarding GLP-1 receptor agonists, the data suggest a possible promising therapeutic effect, based on the assumption that GLP-1 secretion is impaired in patients with PPGL. The principal predictors of remission of glycemic alterations after surgery for PPGL are a lower preoperative body mass index (BMI), a larger tumor, higher preoperative catecholamine levels, and a shorter duration of the disease (under three years). Otherwise, after resection of PPGL, hypoglycemia can occur as the result of an excessive rebound of preoperative hyperinsulinemia. It is a rare, but potentially severe complication reported in a lot of case reports and a few small retrospective studies. Higher 24-h urinary metanephrine levels, longer operative times and larger tumors are predictive factors for hypoglycemia in this setting. In conclusion, alterations of carbohydrate metabolism are clinically relevant manifestations of PPGL before and after surgery, but there is the need to conduct multicenter prospective studies to obtain an adequate sample size, and to allow the creation of shared strategies for the clinical management of these potentially severe manifestations of PPGL.
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Neoplasias das Glândulas Suprarrenais , Intolerância à Glucose , Hipoglicemia , Resistência à Insulina , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/cirurgia , Feocromocitoma/patologia , Estudos Prospectivos , Estudos Retrospectivos , Paraganglioma/cirurgia , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Insulina , Catecolaminas/urina , Hipoglicemia/complicações , Estudos Multicêntricos como AssuntoRESUMO
The mineralocorticoid receptor (MR) acts as an essential regulator of blood pressure, volume status, and electrolyte balance. However, in recent decades, a growing body of evidence has suggested that MR may also have a role in mediating pro-inflammatory, pro-oxidative, and pro-fibrotic changes in several target organs, including the adipose tissue. The finding that MR is overexpressed in the adipose tissue of patients with obesity has led to the hypothesis that this receptor can contribute to adipokine dysregulation and low-grade chronic inflammation, alterations that are linked to the development of obesity-related metabolic and cardiovascular complications. Moreover, several studies in animal models have investigated the role of MR antagonists (MRAs) in preventing the metabolic alterations observed in obesity. In the present review we will focus on the potential mechanisms by which MR activation can contribute to adipose tissue dysfunction in obesity and on the possible beneficial effects of MRAs in this setting.
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Tecido Adiposo , Receptores de Mineralocorticoides , Animais , Obesidade/complicações , Adipocinas , Pressão SanguíneaRESUMO
Several studies argued that cardiovascular evaluation of patients with nonfunctioning adrenal incidentaloma is of particular importance. Therefore, we aimed to evaluate the possibility of stratifying the cardiometabolic risk using metanephrine levels in this setting of patients. A retrospective cross-sectional study was designed, collecting data of metanephrine values in 828 patients with nonfunctioning adrenal incidentaloma, referred to our Division within the University of Turin between 2007 and 2021. The univariate analysis showed associations between urine metanephrines and cardiometabolic variables/parameters, particularly considering the noradrenaline metabolite. At the univariate regression, normetanephrine was associated with metabolic syndrome (OR = 1.13, p = 0.002), hypertensive cardiomyopathy (OR = 1.09, p = 0.026), microalbuminuria (OR = 1.14, p = 0.024), and eGFR < 60 mL/min/1.73 m2 (OR = 1.11, p = 0.013), while metanephrine was associated with microalbuminuria (OR = 1.50, p = 0.008). At multivariate regression, considering all major cardiovascular risk factors as possible confounders, normetanephrine retained a significant association with metabolic syndrome (OR = 1.10, p = 0.037). Moreover, metanephrine retained a significant association with the presence of microalbuminuria (OR = 1.66, p = 0.003). The present study showed a further role for metanephrines in the cardiovascular risk stratification of patients with nonfunctioning adrenal incidentaloma. Individuals with high levels of these indirect markers of sympathetic activity should be carefully monitored and may benefit from an aggressive treatment to reduce their additional cardiometabolic burden.
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Neoplasias das Glândulas Suprarrenais , Hipertensão , Síndrome Metabólica , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/epidemiologia , Estudos Transversais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Metanefrina , Normetanefrina , Feocromocitoma/complicações , Feocromocitoma/epidemiologia , Estudos RetrospectivosRESUMO
Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. In this review, we aimed to discuss and analyze the most important clinical and histopathological tools for predicting recurrence risk in patients affected by pheochromocytomas or paragangliomas. Thus, we compared the main available predictive models, exploring their applications in stratifying patients' risks. In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patients' treatments and follow-ups.
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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.
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Adenoma , Diabetes Mellitus Tipo 2 , Hiperaldosteronismo , Hipertensão , Adenoma/complicações , Aldosterona , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hidrocortisona , Hipertensão/complicações , Masculino , FenótipoRESUMO
A reliable prediction of the recurrence risk of pheochromocytoma after radical surgery would be a key element for the tailoring/personalization of post-surgical follow-up. Recently, our group developed a multivariable continuous model that quantifies this risk based on genetic, histopathological, and clinical data. The aim of the present study was to simplify this tool to a discrete score for easier clinical use. Data from our previous study were retrieved, which encompassed 177 radically operated pheochromocytoma patients; supervised regression and machine-learning techniques were used for score development. After Cox regression, the variables independently associated with recurrence were tumor size, positive genetic testing, age, and PASS. In order to derive a simpler scoring system, continuous variables were dichotomized, using > 50 mm for tumor size, ≤ 35 years for age, and ≥ 3 for PASS as cut-points. A novel prognostic score was created on an 8-point scale by assigning 1 point for tumor size > 50 mm, 3 points for positive genetic testing, 1 point for age ≤ 35 years, and 3 points for PASS ≥ 3; its predictive performance, as assessed using Somers' D, was equal to 0.577 and was significantly higher than the performance of any of the four dichotomized predictors alone. In conclusion, this simple scoring system may be of value as an easy-to-use tool to stratify recurrence risk and tailor post-surgical follow-up in radically operated pheochromocytoma patients.
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Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are "high-risk phenotypes", associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of "non-classical" effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.
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Hiperaldosteronismo , Hipertensão , Aldosterona , Fibrose , Humanos , Hiperaldosteronismo/genética , Hipertensão/genética , Rim/patologiaRESUMO
Objective: Various features have been identified as predictors of relapse after complete resection of pheochromocytoma, but a comprehensive multivariable model for recurrence risk prediction is lacking. The aim of this study was to develop and internally validate an integrated predictive model for post-surgical recurrence of pheochromocytoma. Methods: The present research retrospectively enrolled 177 patients affected by pheochromocytoma and submitted to radical surgery from 1990 to 2016, in nine referral centers for adrenal diseases. Cox regression analysis was adopted for model development, and a bootstrapping procedure was used for internal validation. Results: Variables independently associated with recurrence were tumor size (hazard ratio (HR): 1.01, 95% CI: 1.00-1.02), positive genetic testing (HR: 5.14, 95% CI: 2.10-12.55), age (HR: 0.97, 95% CI: 0.94-0.99), and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) (HR: 1.16, 95% CI: 1.04-1.29). The predictive performance of the overall model, evaluated by Somers' D, was equal to 0.594, and was significantly higher than the ones of any single predictor alone (P = 0.002 compared to tumor size; P = 0.004 compared to genetic testing; P = 0.048 compared to age; P = 0.006 compared to PASS). Internal validation by bootstrapping techniques estimated an optimistic bias of 6.3%, which reassured about a small tendency towards overfit. Conclusions: We proposed a multivariable model for the prediction of post-surgical recurrence of pheochromocytoma, derived by the integration of genetic, histopathological, and clinical data. This predictive tool may be of value for a comprehensive tailoring of post-surgical follow-up in radically operated pheochromocytoma patients.
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Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Humanos , Recidiva Local de Neoplasia/diagnóstico , Feocromocitoma/diagnóstico , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: This study aimed to evaluate the reliability of simple and corrected aldosterone indices for assessing the selectivity and lateralization of adrenal vein sampling (AVS) in patients with primary aldosteronism. METHODS: Data of all consecutive patients with primary aldosteronism who underwent AVS for subtype diagnosis, followed at two Italian referral centers, were analyzed retrospectively. RESULTS: AVS achieved bilateral selectivity in 112/144 patients. Unilateral disease was diagnosed in 60 cases (53.6%) and idiopathic hyperaldosteronism in 52 individuals (46.4%). The aldosterone index (aldosterone ratio between an adrenal vein and the inferior vena cava) showed a high accuracy in predicting selectivity, compared to a cortisol selectivity index of 1.1, and a moderate accuracy, compared to cortisol cut-offs of 2 and 3. The simple aldosterone index showed a moderate accuracy in predicting ipsi/contralateral aldosterone hypersecretion, while lesion side- and hypokalemia-corrected aldosterone index revealed a significant improvement in predicting ipsi/contralateral disease. Moreover, the comparative aldosterone index (aldosterone ratio in the dominant vs the non-dominant adrenal vein) revealed a high accuracy in predicting unilateral primary aldosteronism. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 90%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. CONCLUSIONS: This study demonstrated the diagnostic accuracy of simple and clinical-/imaging-corrected aldosterone indices for adrenal vein sampling in subtype diagnosis of primary aldosteronism and suggests the potential application of these tools to select patients for adrenalectomy when standard indices cannot be performed.
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Hiperaldosteronismo , Hipopotassemia , Aldosterona , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Hiperplasia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Primary aldosteronism (PA) is the most common cause of secondary hypertension. A growing body of evidence has suggested that, beyond its well-known effects on blood pressure and electrolyte balance, aldosterone excess can exert pro-inflammatory, pro-oxidant and pro-fibrotic effects on the kidney, blood vessels and heart, leading to potentially harmful pathophysiological consequences. In clinical studies, PA has been associated with an increased risk of cardiovascular, cerebrovascular, renal and metabolic complication compared to essential hypertension, including atrial fibrillation (AF) and aortic ectasia. An increased prevalence of AF in patients with PA has been demonstrated in several clinical studies. Aldosterone excess seems to be involved in the pathogenesis of AF by inducing cardiac structural and electrical remodeling that in turn predisposes to arrhythmogenicity. The association between PA and aortic ectasia is less established, but several studies have demonstrated an effect of aldosterone on aortic stiffness, vascular smooth muscle cells and media composition that, in turn, might lead to an increased risk of aortic dilation and dissection. In this review, we focus on the current evidence regarding the potential role of aldosterone excess in the pathogenesis of AF and aortic ectasia.
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Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Fibrilação Atrial/etiologia , Fibrilação Atrial/patologia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/patologia , Aldosterona/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/metabolismo , Fibrilação Atrial/metabolismo , Humanos , Hiperaldosteronismo/metabolismoRESUMO
No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess >the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95% CI 5.46-15.71) in males and 13.21 (95% CI 7.52-21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95% CI 1.15-5.44, p = 0.021 for 50-59 vs. <50-year category; HR 3.46, 95% CI 1.67-7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95% CI 0.10-0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.
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We present the case of a 45-year-old woman admitted to our unit with acute heart failure and cardiogenic shock, requiring an intra-aortic balloon pump insertion and inotropes and vasopressors infusion. Despite such treatment, the patient developed multi organ failure and intravascular disseminated coagulation with haemolysis. The initial diagnosis of acute myocarditis was subsequently denied by the finding of bilateral adrenal masses by MRI scan, and urine and plasma metanephrines measurements confirmed a pheochromocytoma (PCC). Genetic analysis revealed a mutation in the neurofibromatosis type 1 (NF1) gene, and an accurate physical examination drew attention to small cafè-au-lait spots, usually associated with this syndrome. PCC diagnosis should be promptly considered in patients presenting with unexplained acute heart failure and cardiogenic shock of unknown origin, considering its life-threatening complications and the good prognosis after radical surgery.
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No research has explored the role of catecholamine metabolites in the stratification of cardiovascular risk. We aimed to evaluate the relationship between urine metanephrines and cardiometabolic risk/complications. In this retrospective cross-sectional study, we collected the data of 1374 patients submitted to the evaluation of urine metanephrines at the City of Health and Science University Hospital of Turin between 2007 and 2015, mainly for investigating the suspicion of secondary hypertension or the secretion of an adrenal lesion. The univariate analysis showed associations between metanephrines and cardiometabolic variables/parameters, particularly considering noradrenaline metabolite. At univariate regression, normetanephrine was associated with hypertensive cardiomyopathy (OR = 1.18, 95% CI 1.11-1.25; p < 0.001) and metabolic syndrome (OR = 1.11, 95% CI 1.03-1.20; p = 0.004), while metanephrine was associated with hypertensive cardiomyopathy (OR = 1.23, 95% CI 1.06-1.43; p = 0.006) and microalbuminuria (OR = 1.30, 95% CI 1.03-1.60; p = 0.018). At multivariate regression, considering all major cardiovascular risk factors as possible confounders, normetanephrine retained a significant association with hypertensive cardiomyopathy (OR = 1.14, 95% CI 1.07-1.22; p < 0.001) and metabolic syndrome (OR = 1.10, 95% CI 1.02-1.19; p = 0.017). Moreover, metanephrine retained a significant association with the presence of hypertensive cardiomyopathy (OR = 1.18, 95% CI 1.01-1.41; p = 0.049) and microalbuminuria (OR = 1.34, 95% CI 1.03-1.69; p = 0.019). The study showed a strong relationship between metanephrines and cardiovascular complications/metabolic alterations. Individuals with high levels of these indirect markers of sympathetic activity should be carefully monitored, and they may benefit from an aggressive treatment to reduce the cardiometabolic risk.