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

Abstract

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.

Keywords: ICD; International Classification of Diseases; SNOMED; Systematized Nomenclature of Medicine; cause of death register; hospital register diagnoses; pathology register; registry-based research.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1

Identification of PPGL patients in area of validation, the North Denmark Region and Central Denmark Region. Notes:aSeven cases of doubt refuted as non-secreting paragangliomas; twenty-four refuted due to weak clinical evidence despite some inconsistencies; and six refuted due to insufficient information to confirm PPGL. bThirty-five cases of doubt confirmed as PPGL based on pathology and clinic despite no lab tests performed (diagnosed at autopsy or by pathologist post-surgery); three confirmed despite no pathological examination (patient abstained from surgery or surgery not technically possibly); and fourteen confirmed due to strong clinical evidence despite some missing data or inconsistencies. cFive refuted as non-secreting paragangliomas; six refuted as workup were insufficient to confirm PPGL. dOne patient with confirmed PPGL who did not fulfill primary or expanded eligibility criteria was reported by endocrine specialist (MGR) at Department of Endocrinology at Aalborg University Hospital. Abbreviation: PPGL, pheochromocytoma and catecholamine-secreting paraganglioma.