Original ArticleIncidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review
Introduction
Pheochromocytomas (PCC) and sympathetic paragangliomas (sPGL) are rare neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla and the extra-adrenal sympathetic paraganglia, respectively. Histologically these tumors are identical and they share the capacity to synthesize and release catecholamines (dopamine, norepinephrine and epinephrine) [[1], [2], [3]]. Uncontrolled hypersecretion of catecholamines by these tumors may evoke typical signs and symptoms such as paroxysmal hypertension, sweating and tachycardia, and can result in severe cardiovascular morbidity and mortality [4]. Surgical resection is the treatment of choice, as it represents the only option for cure [5].
In the past, a substantial proportion of PCC/sPGL was not diagnosed during life but discovered post mortem during autopsy [6]. Recent years have seen a tremendous rise in the number of imaging studies being ordered in clinical practice [7, 8], as well as more frequent assessment of metanephrines in plasma or urine [9]. The sensitivity of biochemical testing and imaging techniques for detecting PCC/sPGL has also improved substantially over the past two decades [[10], [11], [12]]. It is conceivable that these changes in diagnostic procedures have influenced the detection rate of PCC/sPGL during life in recent years. However, epidemiological data on PCC/sPGL, and particularly on its incidence rate, are surprisingly scarce.
Our objective was to determine the annual incidence rate of PCC/sPGL during the past two decades in the Netherlands. To this end we conducted a retrospective nationwide pathology study. We hypothesized that the annual incidence rate has increased during the past two decades. For comparison of our data, we performed a systematic review of the literature on previously reported nationwide incidence rates of PCC/sPGL.
Section snippets
Systematic review
In order to identify articles published in peer-reviewed medical journals we conducted a systematic search of PubMed/MEDLINE and Embase, in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [13]. We used the following search terms: pheochromocytoma, paraganglioma, epidemiology, incidence, prevalence, autopsy, and post mortem examination (see Supplemental data for detailed information). The search was carried out on November 10, 2016. We
Systematic review
After removal of duplicates, the literature search yielded 2095 papers. After reading titles and abstracts we excluded 2025 articles. We excluded an additional 67 papers after reading the full texts (Supplemental Fig. 1). We finally included three papers in the present systematic review [[19], [20], [21]].
The three publications included in this systematic review were published between 1964 and 1988. Two of the three used a national disease registry for data extraction. One study used a
Discussion
We here describe the epidemiology of PCC/sPGL in the Netherlands during two decades, i.e. from 1995 to 2015. We found a significant increase of the ASR of PCC/sPGL, which coincided with a reduction in tumor size and a higher age at the time of initial diagnosis.
The incidence rates in the present study are derived from the largest series of patients with PCC/sPGL published so far, and are considerably higher than previously reported. There is, however, a lack of good quality estimates with
Declaration of interest
All authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Author contributions
All authors meet all the criteria for authorship in the ICMJE Recommendations.
Annika M.A. Berends: Literature search, figures, study design, data collection, data analysis, data interpretation, writing.
Edward Buitenwerf: Literature search, figures, study design, data collection, data analysis, data interpretation, writing.
Ronald R. de Krijger: Data analysis, data interpretation, writing.
Nic J.G.M. Veeger: Data analysis, data interpretation, writing.
Anouk N.A. van der Horst-Schrivers: Data
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