No abstract

Objective: Simple unconventional indices did not demonstrate a satisfactory accuracy for diagnosing unilateral primary aldosteronism when adrenal vein sampling is not bilaterally selective. This study aimed to evaluate the reliability of clinical/imaging-corrected unconventional indices for adrenal vein sampling in predicting unilateral primary aldosteronism.Methods: Data of all consecutive patients with primary aldosteronism subtyped with adrenal vein sampling, referred to two Italian centers, were analyzed retrospectively. All patients with proved unilateral aldosterone hypersecretion underwent adrenalectomy.Results: Unilateral disease was diagnosed in 58 cases (54.2%) and idiopathic hyperaldosteronism in 49 individuals (45.8%). The monoadrenal index (aldosterone-to-cortisol ratio in the adrenal vein) showed high accuracy in predicting ipsilateral disease and moderate accuracy in predicting contralateral aldosterone hypersecretion. The monolateral index (aldosterone-tocortisol ratio in the adrenal vein vs. peripheral blood) revealed moderate accuracy in predicting ipsilateral disease and high accuracy in predicting contralateral aldosterone hypersecretion. Lesion side-and hypokalemia-corrected ROC curves for these unconventional indices revealed a significant improvement in the reliability of predicting ipsilateral/ contralateral disease, reaching high accuracy in all models. 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 95%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. Conclusion:This study demonstrated the high diagnostic accuracy of clinical-/imaging-corrected unconventional indices for adrenal vein sampling in the diagnosis of primary aldosteronism subtypes and suggests the use of these adjusted indices to select patients for adrenalectomy when adrenal vein sampling is not bilaterally selective.

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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.

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.