Background
Minimally invasive adrenalectomy represents the treatment of choice of pheochromocytoma (PCC). For large or invasive PCCs, an open approach is currently recommended, in order to ensure ...complete tumor resection, prevent tumor rupture, avoid local recurrence, and limit perioperative hemodynamic instability. The aim of this study is to analyze perioperative outcomes of laparoscopic adrenalectomies (LAs) for large adrenal PCCs.
Methods
All consecutive LAs for PCC performed at a single institution between 1998 and 2020 were included. Two groups were defined: lesions larger (group 1) and smaller (group 2) than 5 cm. Short-term outcomes were compared in order to find any significant difference between the two groups.
Outcomes
One hundred fourteen patients underwent LA during the study period: 46 for lesions larger and 68 for lesions smaller than 5 cm. No significant differences were found in patients’ characteristics, median operative time, conversion rate, intraoperative hemodynamic and metabolic parameters, postoperative intensive care unit (ICU) admission rate, complications rate, and length of hospital stay. Long-term oncologic outcomes were similar, with a recurrence rate of 5.1% in group 1 vs 3.6% in group 2 (
p
= 1).
Conclusion
Minimally invasive adrenalectomy seems to be safe and effective even in large PCC. The recommendation to prefer an open approach for large PCCs should probably be reconsidered.
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.
Summary
Objective
To study the effect of a iodine load on thyroid function of patients with ischaemic heart disease (IHD) and the long‐term influence of unknown subclinical hyperthyroidism.
Context
...Subclinical hyperthyroidism is considered an independent risk factors for cardiovascular morbidity of patients with IHD. They routinely undergo coronary angiography with iodine contrast media (ICM) which may induce or even worsen hyperthyroidism.
Design
A cross‐sectional study followed by a longitudinal study on patients with subclinical hyperthyroidism.
Patients
810 consecutive IHD outpatients without known thyroid diseases or treatment with drugs influencing thyroid activity undergoing elective coronary angiography.
Measurements
We evaluated thyroid function either before and 1 month after ICM; patients with thyrotoxicosis at baseline or after ICM were then followed up for 1 year.
Results
58 patients had hyperthyroidism at baseline (HB, 7.2%), independently associated to FT4 levels, thyroid nodules and family history of thyroid diseases. After ICM, the prevalence of hyperthyroidism was 81 (10%). Hyperthyroidism after ICM was positively predicted by baseline fT4 levels, thyroid nodules, age over 60, male gender, family history of thyroid diseases. Three months after ICM, 34 patients (4.2%) still showed hyperthyroidism (22 from HB, 13 treated with methimazole). One year after ICM, hyperthyroidism was still present in 20 patients (2.5%, all from HB, 13 treated).
Conclusions
The prevalence of spontaneous subclinical hyperthyroidism in IHD is surprisingly elevated and is further increased by iodine load, particularly in patients with thyroid nodules and familial history of thyroid diseases, persisting in a not negligible number of them even after one year.
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.
The simultaneous measurement of dexamethasone and cortisol has proven the ability to increase the diagnostic performance of the overnight dexamethasone-suppression test. Furthermore, the therapeutic ...drug monitoring of administered corticosteroid drugs could represent a crucial tool for investigating unexpected variations of steroid hormones' circulating levels. In this work, an LC-MS/MS method for the quantification of cortisol, cortisone, dexamethasone and six additional exogenous corticosteroids in the serum/plasma matrix was developed and validated in compliance with the ISO/IEC requirements. To assess the efficiency of the validated method, serum samples of 75 patients undergoing the dexamethasone-suppression test and 21 plasma samples of patients under immunosuppressive treatment after kidney transplant were analyzed. In all dexamethasone-suppression test samples, it was possible to measure the circulating levels of cortisol, cortisone and dexamethasone. Concentrations of the latter were for all tested patients above the proposed cutoff for the dexamethasone-suppression test's results, and the cortisol concentrations showed good correlation with the ones measured by routine immunometric analysis, therefore confirming the screening outcome for all enrolled patients. Prednisone was detected and quantified in all enrolled patients, confirming the use of such a corticosteroid for immunosuppressive therapy. Thanks to these two applications, we proved the overall performance of the developed LC-MS/MS method for four target analytes. The future implementation of such an analytical tool in the clinical biochemistry laboratory's routine will guarantee a single and versatile tool for simultaneously monitoring dexamethasone-suppression-test results and corticosteroid drugs' administration.
Autoimmune rheumatological diseases’ incidence and prevalence have risen over the last decades and they are becoming increasingly important worldwide. Thyroid autoimmune diseases share with them an ...imbalance in the immune system that lead to a pro-inflammatory environment. Usually this is the result of a multi-factorial process. In fact, it includes not only a possible genetic predisposition, but also environmental causes like microbiota dysbiosis, diet rich in processed foods, exposure to toxicants and infections. However, many aspects are currently under study. This paper aims to examine the factors that participate in the developing of rheumatological and thyroid autoimmune diseases. Moreover, as glucocorticoids still represent a leading treatment for systemic autoimmune rheumatological diseases, our secondary aim is to summarize the main effects of glucocorticoids treatment focusing on iatrogenic Cushing’s syndrome and glucocorticoids’ withdrawal syndrome.
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.
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.
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 m
(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.