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

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.

Pheochromocytoma in Denmark during 1977-2016: validating diagnosis codes and creating a national cohort using patterns of health registrations.

BACKGROUND: Pheochromocytoma and catecholamine-secreting paraganglioma (PPGL) are rare but potentially life-threatening tumors. We aimed to validate diagnosis codes for PPGL in the Danish National Patient Registry, the Danish National Pathology Registry, and the Danish Registry of Causes of Death and to create a national cohort of incident PPGL patients by linking these three registries. PATIENTS AND METHODS: We obtained data from the three abovementioned registries for all individuals registered with pheochromocytoma or catecholamine hypersecretion in Denmark during 1977-2016 (average population 5.30 million). We then reviewed health records for all individuals living in the North Denmark Region and Central Denmark Region (average population 1.75 million) to validate the diagnosis of PPGL. We tested a number of algorithms for accurately identifying true cases of PPGL to maximize positive predictive values (PPVs) and completeness. The best algorithm was subsequently validated in an external sample. RESULTS: We identified 2626 individuals with a PPGL diagnosis code in Denmark, including 787 (30.0%) in the North Denmark Region and Central Denmark Region. In this subsample, we retrieved the health records of 771/787 (98.0%) individuals and confirmed 198 incident PPGL patients (25.3%). The PPV of PPGL diagnosis codes was 21.7% in the Danish National Patient Registry, 50.0% in the Danish Registry of Causes of Death, and 79.5% in the Danish National Pathology Registry. By combining patterns of registrations in the three registries, we could increase the PPV to 93.1% (95% confidence interval [CI]: 88.5-96.3) and completeness to 88.9% (95% CI: 83.7-92.9), thus creating a national PPGL cohort of 588 patients. PPV for the optimal algorithm was 95.3% (95% CI: 88.5-98.7) in the external validation sample. CONCLUSION: Diagnosis codes for pheochromocytoma had low PPV in several individual health registries. However, with a combination of registries we were able to identify a near-complete national cohort of PPGL patients in Denmark, as a valuable source for epidemiological research.