Pheochromocytoma and paraganglioma: clinical feature-based disease probability in relation to catecholamine biochemistry and reason for disease suspicion

Abstract

Objective Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease. Design and methods Patients were tested for PPGLs because of signs and symptoms, an incidental mass on imaging or routine surveillance due to previous history or hereditary risk. Patients with (n = 245) compared to without (n = 1820) PPGLs were identified on follow-up. Differences in presenting features were then examined to assess the probability of disease and relationships to catecholamine excess. Results Hyperhidrosis, palpitations, pallor, tremor and nausea were 30–90% more prevalent (P < 0.001) among patients with than without PPGLs, whereas headache, flushing and other symptoms showed little or no differences. Although heart rates were higher (P < 0.0001) in patients with than without PPGLs, blood pressures were not higher and were positively correlated to BMI, which was lower (P < 0.0001) in patients with than without PPGLs. From these differences in clinical features, a score system was established that indicated a 5.8-fold higher probability of PPGLs in patients with high than low scores. Higher scores among patients with PPGLs were associated, independently of tumor size, with higher biochemical indices of catecholamine excess. Conclusions This study identifies a complex of five signs and symptoms combined with lower BMI and elevated heart rate as key features in patients with PPGLs. Prevalences of these features, which reflect variable tumoral catecholamine production, may be used to triage patients according to likelihood of disease.

Catecholamine physiology and its implications in patients with COVID-19

“… 6 Consequently, catecholamine excess states such as PPGL can cause substantial dysregulation of physiological systems, and lead to pronounced changes in pulmonary (vasoplegia), coronary (myocardial infarction), cerebrovascular (stroke), and remaining systemic vascular tone (hypertension), as well as myocardial disease (cardiomyopathies), tachyarrhythmias (benign and fatal), hypercoagulability (thromboembolism), immune dysregulation (cytokine storm), and diabetogenic states; these outcomes are the same as the risk factors that lead to adverse outcomes from COVID-19. 2 , 6 , 7 , 8 , 9 , 10 , 11 , 12 These findings suggest that catecholamines might be key mediators in COVID-19. As PPGL is an extensively studied catecholamine excess state, we believe that it might serve as a practical model for exploring the pathological and beneficial actions of catecholamines in patients with COVID-19.…”

“… 44 , 45 This observation is also relevant in patients with COVID-19 with excess catecholamines, because blood pressure—even among patients with PPGL—has been shown to positively correlate with body-mass index. 9 On the other hand, some patients with catecholamine excess and severe COVID-19 infection who would have otherwise developed distributive (septic) or cardiogenic shock might be paradoxically protected from developing a shock state due to the vasoconstrictive and cardio-stimulatory effects of excess circulatory catecholamines; these physiological effects are relevant to patients with COVID-19 who might have compensated shock with the provision of endogenous or exogenous adrenaline or noreadrenaline. 14 …”

“… 14 Up to 71% of patients with PPGL die of cardiovascular causes, with 19·3% experiencing acute, sometimes fatal, cardiovascular complications. 9 , 10 , 48 These complications include heart failure, myocardial infarction, arrhythmias, and ischaemic and haemorrhagic strokes. 7 , 10 Catecholamines have chronic and acute influences on the cardiovascular system.…”

Pheochromocytoma Concealed By Chronic Methamphetamine Abuse

“…Over the past 2 decades, as PCCs have increasingly been discovered based on reasons other than presenting signs and symptoms, it has become evident that hypertension is not consistently present in patients with these tumors (10,11). Even when hypertension and other signs and symptoms of possible catecholamine excess are present, these are nonspecific (3), and as in the present easily attributed to other causes. Thus, as it turned out, it was the digestive complaints (nausea and vomiting) that prompted an ultrasound and the incidental finding of an adrenal mass, and from this justification for biochemical testing for PCC.…”

“…Classical symptoms of headache, sweating, and palpitations usually occur in paroxysms while hypertension is often sustained (1). However, such signs and symptoms are nonspecific and the presence of hypertension on its own is not useful for clinical suspicion (3).…”