Il ruolo della renina plasmatica nella titolazione della terapia sostitutiva con mineralcorticoidi in pazienti affetti da insufficienza surrenalica primaria

SommarioL'ottimizzazione della terapia con mineralcorticoidi in pazienti con insufficienza surrenalica primaria non ha ancora trovato consenso universale. Questa rassegna riporta i dati di una vasta coorte di pazienti affetti da insufficienza surrenalica primaria con l'obiettivo di esplorare la relazione tra la dose sostitutiva dei mineralcorticoidi (MC), la concentrazione plasmatica di renina (CPR) e variabili cliniche ambulatoriali (elettroliti, pressione sanguigna, PA, e parametri antropometrici) al fine di identificare marcatori utili per guidare la titolazione della dose MC. I risultati hanno mostrato un'estrema variabilità nei valori di CPR e nella dose di MC. Nell'analisi univariata, la dose di MC era direttamente proporzionale alla CPR ma non correlava con i livelli di PA. Utilizzando modelli di regressione multipla, il sodio era l'unica variabile utile a predire la CPR. Nell'analisi longitudinale, la variazione della dose di MC era correlata alla variazione dei livelli sierici di potassio ma non alla PA o alla CPR. In conclusione, la relazione tra la dose di MC e la CPR è complessa e, pertanto, la titolazione dei MC non dovrebbe essere basata solo sulla normalizzazione della CPR, ma anche su parametri clinici come la PA e la concentrazione di elettroliti

Il ruolo della renina plasmatica nella titolazione della terapia sostitutiva con mineralcorticoidi in pazienti affetti da insufficienza surrenalica primaria

SommarioL'ottimizzazione della terapia con mineralcorticoidi in pazienti con insufficienza surrenalica primaria non ha ancora trovato consenso universale. Questa rassegna riporta i dati di una vasta coorte di pazienti affetti da insufficienza surrenalica primaria con l'obiettivo di esplorare la relazione tra la dose sostitutiva dei mineralcorticoidi (MC), la concentrazione plasmatica di renina (CPR) e variabili cliniche ambulatoriali (elettroliti, pressione sanguigna, PA, e parametri antropometrici) al fine di identificare marcatori utili per guidare la titolazione della dose MC. I risultati hanno mostrato un'estrema variabilità nei valori di CPR e nella dose di MC. Nell'analisi univariata, la dose di MC era direttamente proporzionale alla CPR ma non correlava con i livelli di PA. Utilizzando modelli di regressione multipla, il sodio era l'unica variabile utile a predire la CPR. Nell'analisi longitudinale, la variazione della dose di MC era correlata alla variazione dei livelli sierici di potassio ma non alla PA o alla CPR. In conclusione, la relazione tra la dose di MC e la CPR è complessa e, pertanto, la titolazione dei MC non dovrebbe essere basata solo sulla normalizzazione della CPR, ma anche su parametri clinici come la PA e la concentrazione di elettroliti

Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes

Endothelial dysfunction (ED) plays a role in diabetic cardiovascular complications. Hyperglycemia increases cytockines involved in vascular inflammation. Inhibition of phosphodiesterase type 5 (PDE5) exerts a relaxation on corpora cavernosa and has cardioprotective properties. The effect of chronic sildenafil treatment, on ED markers and metabolic parameters in a non-randomized study on men with type 2 diabetes (T2DM), was investigated

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early

Somatostatin Analogue Therapy in MEN1-Related Pancreatic Neuroendocrine Tumors from Evidence to Clinical Practice: A Systematic Review

Neuroendocrine neoplasms (NENs) are relatively rare and complex tumors that can be sporadic or hereditary, as in the context of multiple endocrine neoplasia type 1 (MEN1) where patients display a 70% lifelong risk of developing a pancreatic NENs (pNENs). To date, specific personalized treatment for pNENs in patients with MEN1 are lacking. The aim of this study was to systematically analyze the efficacy and safety of somatostatin analogue (SSA) treatment in patients affected by MEN1-related pNENs. We performed a systematic review of the literature, searching for peer-reviewed articles on SSA (octreotide or lanreotide) treatment in MEN1 associated with pNENs. We selected 20 studies with a pooled population of 105 MEN1 patients with pNENs. Females were 58.5%, median age was 44 years (18–73). TNM stage at diagnosis was stage I–II in 84.8% and stage IV in 15.2%. The overall response rate (SD+PR+CR) was achieved in 88.3% of cases, with stable disease in 75.6% and objective response in 12.7% of patients. The safety profile was favorable with both SSA agents. SSAs appear to be an effective and safe treatment option for MEN1-related pNEN, either at localized or advanced stages.Depto. de MedicinaFac. de MedicinaTRUEMinisterio de Ciencia e Innovación (España)pu

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven

Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas – recently defined as possible autonomous cortisol secretion (pACS) – has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking. Subjects and methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind. Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 nonfunctioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMIBSA) was increased in pACS compared to NFA (P=0.006) and mildly correlated to the post-DST cortisol level (rho=0.347; P=0.004). The post-DST cortisol levels explained up to 13.7% of LVMIBSAvariance (P=0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P=0.001) and worse arterial stiffness assessed by pulse wave velocity (P=0.033). Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition

Ruolo diagnostico, prognostico e predittivo di risposta del NETest nelle neoplasie neuroendocrine

Il NETest è una metodica di biologia molecolare e, in particolare, di biopsia liquida, applicata alle neoplasie neuroendocrine (NEN), che si propone come nuovo biomarcatore altamente sensibile e specifico. Il NETest consente una sorta di gene signature del tumore, definendone il profilo trascrizionale mRNA, estratto dal sangue periferico. L’applicazione pratica è nella diagnosi, dove il NETest sembra identificare anche piccoli tumori localizzati, nella definizione prognostica, con l’identificazione dei tumori con maggiore tendenza alla progressione e alla recidiva post-chirurgica, nella riposta ai trattamenti, con l’identificazione precoce di progressione nel corso di terapie anti-tumorali. A fronte di risultati iniziali estremamente promettenti, il NETest necessita di una conferma su larga scala, in ampie casistiche multicentriche

Diabetic cardiomiopathy progression is triggered by miR122-5p and involves extracellular matrix: a 5-year prospective study

The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis

Quality of Life in Patients with Neuroendocrine Neoplasms: The Role of Severity, Clinical Heterogeneity and Resilience

Context Although health-related quality of life (HRQoL) is a fundamental outcome in oncological clinical trials, its evaluation in the neuroendocrine neoplasm (NEN) research field is still limited. Objectives This study assessed the role of clinical severity (i.e., presence or absence of metastasis and lines of therapies) and heterogeneity (i.e., primary site, types of therapy, biology and surgery) of NEN in relation to HRQoL, as well as resilience as a moderator between clinical severity and HRQoL. Design Cross-sectional multicentric study. Setting Italian university hospitals. Patients 99 Italian patients (53 men and 46 women) with a NEN ranged in age from 22 to 79 years old. Main Outcome Measure Severity and heterogeneity of NENs, HRQoL and resilience. Results The presence of metastasis and a greater number of therapies affected the global health and some physical symptoms. Resilience was associated with global health, functional status and some physical symptoms, and moderated the impact of metastases on constipation and of the multiple therapies on diarrhea and financial problems. Patients with NEN in districts other than the gastro-entero-pancreatic system and those in follow-up perceived fewer physical symptoms than their counterparts. Patients with a sporadic NEN perceived their functional status, global health and disease-related worries as better than those with a hereditary NEN. Patients who underwent surgery were lower in constipation than their counterparts. Conclusion These findings highlight the need to assess the relationships between the clinical severity and heterogeneity of NEN with HRQoL and the role of resilience in improving patients’ HRQoL