Seventy years of pheochromocytomas and paragangliomas in Argentina. The FRENAR database.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.

[Diagnostic approach of pheochromocytomas and paragangliomas]. / Enfoque diagnóstico de feocromocitomas y paragangliomas.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours associated with high morbidity and mortality. Recognizing the clinical presentation is the first step for diagnosis. Biochemical studies may determine an excess of catecholamines and their metabolites. However, the available tests offer varying diagnosis precision. Computed tomography and magnetic resonance are highly sensitive for locating these tumours. Functional tests are reserved for when metastatic and multifocal disease are suspected. One third of the patients have a germline mutation and many genes are involved in the development of these tumours.

Current strategies to achieve further cardiac and renal protection through enhanced renin-angiotensin-aldosterone system inhibition.

An incomplete inhibition of the renin angiotensin aldosterone system (RAAS) may be responsible for the residual organ damage and event rate that still occur in spite of an apparent blood pressure control in patients with hypertension, diabetes, chronic kidney disease and heart failure treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Additional antiproteinuric effect in diabetic and non diabetic chronic kidney disease, and reduction in hospitalizations in patients with heart failure already receiving a single RAAS antagonist, has been achieved by incremental inhibition of the RAAS with dual therapy or uptitration of an individual agent above conventional dosages. However, the synergistic increase in plasma renin activity (PRA) and the angiotensin II escape could reduce the expected benefit obtained with dual therapy. Results from ONTARGET showing a lack of additional outcome benefit over monotherapy, with a concomitant increase risk of hyperkalemia, renal impairment, and hypotension, discourage the use of the ACEI/ARB combination in patients at high risk of cardiovascular events. This occured despite a lower albumin excretion in dual versus single RAAS blockade, indicating that an incremental antiproteinuric effect is not automatically translated into clinical outcome benefits. The efficacy and safety of ACEI/ARB combination versus monotherapy in patients with overt proteinuria is currently evaluated by LIRICO and VA NEPHRON-D clinical trials. The long lasting direct renin inhibitor aliskiren, acting at the first and rate limiting step of the RAAS cascade, prevents the reactive increase in PRA when combined with ACEIs, ARBs or diuretics. The ASPIRE HIGHER programme, involving more than 35,000 patients with hypertension, heart failure, kidney disease and diabetes, is currently evaluating the efficacy and safety of aliskiren on top of standard therapy. The clinical benefit of adding mineralocorticoid receptor blockers (MRBs) in the control of resistant hypertension, proteinuric kidney diseases, and prevention of mortality in patients with heart failure on top of conventional treatment, evidences the pathogenic role of inadequately suppressed aldosterone as a cause of suboptimal response to conventional RAAS inhibition. The present review will focus on the pathophysiological ground, and the evidence provided by clinical trials assessing the efficacy and safety of recent strategies for the prevention of cardiovascular events and target organ damage progression via enhanced RAAS inhibition.

Parathyroid carcinoma presenting as a giant mediastinal retrotracheal functioning cyst.

Parathyroid carcinoma is a rare malignancy of the parathyroid glands, and is the cause of primary hyperparathyroidism in fewer than one percent of cases. Symptoms are mainly due to local compression or hypercalcaemia secondary to markedly elevated parathyroid hormone levels. A minority of patients remain asymptomatic. Mediastinal parathyroid cysts are infrequent and may or may not be functioning. We present an 84-year-old woman with a giant functioning cystic parathyroid carcinoma located in the middle mediastinum. We performed a thorough MEDLINE and LILACS database search on published cases of parathyroid carcinoma and functioning parathyroid cysts, and found no case report with identical features to the one presented here.