Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study

Abstract

Context Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare catecholamine-secreting tumors but recent studies suggest increasing incidence. Traditionally, PPGL are described to present with paroxysmal symptoms and hypertension, but existing data on clinical presentation of PPGL come from referral centers. Objective We aimed to describe time trends in clinical presentation and incidence of PPGL in a population-based study. Methods We conducted a nationwide retrospective cohort study of a previously validated cohort of 567 patients diagnosed with PPGL in Denmark 1977-2015. We collected clinical data from medical records of a geographic subcohort of 192 patients. We calculated age-standardized incidence rates (SIRs) and prevalence for the nationwide cohort and descriptive statistics on presentation for the subset with clinical data. Results SIRs increased from 1.4 (95% CI 0.2-2.5) per million person-years in 1977 to 6.6 (95% CI 4.4-8.7) per million person-years in 2015, corresponding to a 4.8-fold increase. The increase was mainly due to incidentally found tumors that were less than 4 cm and diagnosed in patients older than 50 years with no or limited paroxysmal symptoms of catecholamine excess. On December 31, 2015, prevalence of PPGL was 64.4 (CI 95% 57.7-71.2) per million inhabitants. Of 192 patients with clinical data, 171 (89.1%) had unilateral pheochromocytoma, while unilateral paraganglioma (n = 13, 6.8%) and multifocal PPGL (n = 8, 4.2%) were rare. Conclusion Incidence of PPGL has increased 4.8-fold from 1977 to 2015 due to a “new” group of older patients presenting with smaller incidentally found PPGL tumors and few or no paroxysmal symptoms.

Incidence, Clinical Presentation and Trends in Indication for Diagnostic Work-Up of Small Intestinal and Pancreatic Neuroendocrine Tumors

“…As the presented data illustrate, incidental findings on imaging constitute an increasing challenge in everyday clinical practice. It has been shown that neuroendocrine incidentalomas originating from areas such as the pituitary gland, adrenal medulla or appendix seem to have a more indolent behavior compared to the symptomatic ones of the same primary site [8,25,26]. In contrast to these findings, our data show that incidental discovered siNETs seem to have a phenotype comparable to the symptomatic discovered disease.…”

Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

“…Currently, we only have some expert opinions suggesting that patients with poorly controlled diabetes or complicated controlled diabetes and hypertension, as well as patients with unexplainable bone fragility or severe osteoporosis, should be screened for hypercortisolism (2,30,31). Consistent with the hypothesis of a current underestimation of the number of patients with adrenal diseases, the incidence of paraganglioma (PGL) has increased 4.8 times from 1977 to 2015, which is likely due to its recognition in patients with PGL found in small incidentally discovered adrenal masses and few or no paroxysmal symptoms (22). This finding suggests that current guidelines, based on old data, may not be adequate to detect patients with PGL seen in daily clinical care today.…”

“…Thus, optimizing the accuracy of screening tests has been advocated in order to avoid overdiagnosing and to individuate true positive cases. In this sense, recent findings that various adrenal disorders have a genetic basis and that genetic variants may predispose to the development of these diseases could lead to a better focus on providing screening tests to the individuals at risk (20)(21)(22)(23).…”

Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry

“…Traditionally considered a “one in a million” disease, PPGLs have shown a rising incidence during the last 40 years, from 1.4 per million person-years in 1977 to 6.6 in 2015, constituting a 4.8-fold increase [ 6 ]. The upsurge is largely attributable to smaller tumors in patients with few/no symptoms, suggesting that an intensified use of clinical imaging techniques might contribute to this increase.…”