Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review

doi:10.1016/j.ejim.2018.01.015

European Journal of Internal Medicine

Volume 51, May 2018, Pages 68-73

https://doi.org/10.1016/j.ejim.2018.01.015 Get rights and content

Highlights

•
Up-to-date epidemiological data on PCC/sPGL are lacking.
•
The incidence rate of PCC/sPGL has increased significantly during the past two decades.
•
This rise in incidence rate is accompanied by a reduction in tumor size and a higher age at diagnosis.
•
The observed epidemiological changes are most likely the result of more intensified use of better diagnostics.

Abstract

Introduction

Recent years have seen major changes in clinical practice which may have affected the incidence rates of pheochromocytoma(PCC)/sympathetic paraganglioma(sPGL). There is, however, a lack of up-to-date information describing trends in these incidence rates.

Methods

We searched the Dutch pathology registry to identify all histopathologically confirmed cases of PCC/sPGL diagnosed between 1995 and 2015. We calculated incidence rates according to age category as well as age-standardized incidence rates (ASR). We also searched Medline and Embase to find data on nationwide incidence rates of PCC/sPGL.

Results

The nationwide pathology study revealed a total of 1493 patients with either PCC or sPGL. The ASR for PCC increased from 0.29 (95% CI: 0.24–0.33) to 0.46 (95% CI: 0.39–0.53) per 100,000 person-years in the periods 1995–1999 and 2011–2015, respectively. For sPGL the ASR in these same periods were 0.08 (95% CI: 0.06–0.10) and 0.11 (95% CI: 0.09–0.13) per 100,000 person-years, respectively. Concomitantly, PCC size decreased (β −0.17; P < .001) and age at diagnosis increased (β 0.13; P = .001). Our systematic search yielded 3 papers reporting on a total of 530 PCC/sPGL cases, showing a combined annual incidence rate varying from 0.04 to 0.21 per 100,000 person-years.

Conclusion

Incidence rates of PCC/sPGL have increased significantly over the past two decades. This trend coincides with a higher age and a smaller tumor size at diagnosis. Most likely these observations are at least in part the result of changes in clinical practice during the study period, with a more intensified use of both imaging studies and biochemical tests for detecting PCC/sPGL.

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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Carbon dot-based fluorescent probe for early diagnosis of pheochromocytoma through identification of circulating tumor cells
2024, Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
Pheochromocytoma (PCC), as a rare neuroendocrine tumor, is often missed or misdiagnosed because of its atypical clinical manifestations. To realize the early accurate diagnosis of PCC, we have selected circulating tumor cells (CTCs) with more complete biological information as biomarkers and developed a simple and novel fluorescence cytosensor. Octreotide-2,2′,2′′,2′’’- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) modified magnetic Fe₃O₄ and signal amplification CDs@SiO₂ nanospheres are prepared to capture and detect PCC-CTCs from peripheral blood via binding to the somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. During the detection process, the target cells were separated and enriched by magnetic capture probes (Fe₃O₄-DOTA), and then signal probes (CDs@SiO₂-DOTA) could also specifically bound to target cells to form the sandwich-like structure for fluorescence signal output. The proposed fluorescence cytosensor has revealed good sensitivity and selectivity for quantitative analysis of PCC-CTCs in the concentration of 5–1000 cells mL⁻¹ with a LOD of 2 cells mL⁻¹. More importantly, designed fluorescence cytosensor has shown good reliability and stability in complex serum samples. This strategy provides a new way for detection of PCC-CTCs.
A Woman with Bilateral Pheochromocytoma and Tuberous Sclerosis Complex
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Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Here, we report an unusual case of synchronous PPGL in an asymptomatic patient with tuberous sclerosis complex (TSC).
A 49-year-old woman with a history of TSC and end-stage renal disease was referred for evaluation of bilateral adrenal and retroperitoneal masses. She denied chest pain, palpitations, headaches, or previous hypertensive crisis. The laboratory test results showed a plasma normetanephrine level of 20.20 nmol/L (normal range, 0.00-0.89 nmol/L) and plasma chromogranin A level Chromogranin A (CgA) levels of 1518 ng/mL (normal range, 0-103 ng/mL). The plasma metanephrine level was normal. After α-blockade, the patient underwent bilateral adrenalectomy and retroperitoneal mass excision. Pathology confirmed these lesions to be pheochromocytoma and composite paraganglioma/ganglioneuroma, respectively. Her plasma normetanephrine level normalized postoperatively, and the chromogranin A levels improved to 431 ng/mL.
Routine imaging has increased the incidental diagnosis of PPGL. Diagnostic workup includes measurement of the urinary and/or plasma metanephrine and catecholamine levels followed by tumor localization. Patients with young age, syndromic lesions, bilateral PPGL, or unilateral disease with a positive family history should have genetic testing. Definitive treatment is surgical after α-blockade.
This case highlights a rare presentation of bilateral PPGL in a patient with TSC.
Functional retroperitoneal paraganglioma invading the inferior vena cava in the elderly, a case report and literature review
2023, International Journal of Surgery Case Reports
Phaeochromocytomas and paragangliomas are rare neuroendocrine neoplasms that grow outside the adrenal gland and arise from the primitive neural crest cells. The retroperitoneal location is extremely rare with an incidence of 2–8 per million.
Here we report a case of an 80 years old man presenting with abdominal pain and vomiting associated with hypertensive peaks and weight loss. CT scan showed a retroperitoneal para-aortic tumor invading the inferior vena cava, with significantly elevated urinary catecholamine levels. Histopathological and immunohistochemistry examinations confirmed the diagnosis of paraganglioma. A medical preparation by alpha-blockers was performed. Complete resection of the tumor with the reconstruction of the vena cava was achieved without postoperative complications. After surgery, blood pressure and HbA1c were on the targets and the urinary catecholamine levels were normal.
The diagnosis of paragangliomas is suspected by clinical symptoms in the case of functional paragangliomas and the confirmation is biological by the plasmatic or urinary catecholamines. Non-functional paragangliomas often represent a diagnostic challenge. In our case, the large size, the location of the tumor, and the invasion of adjacent structures represented a surgical challenge to perform a complete resection.
In the elderly, this pathology is quite uncommon. Retroperitoneal paraganglioma is a rare location of this type of tumor. Endocrinologists, surgeons, and anesthesiologists should work together to ensure an appropriate diagnosis and treatment of paraganglioma. The gold standard treatment is the complete resection after a medical preparation.
Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes
2023, International Journal of Cardiology
There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS.
We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS.
Among the 18 patients with a median age of 50 years (Q1-Q3: 40–61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15–33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days.
PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed.
T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.
Paragangliomas and Pheochromocytomas: Positron Emission Tomography/Computed Tomography Diagnosis and Therapy
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Back to Biochemistry: Evaluation for and Prognostic Significance of SDH Mutations in Paragangliomas and Pheochromocytomas
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Original ArticleIncidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review

Highlights

Abstract

Introduction

Methods

Results

Conclusion

Introduction

Section snippets

Systematic review

Systematic review

Discussion

Declaration of interest

Funding

Author contributions

Lancet

Endocr Pract

Semin Oncol

Cancer Cell

Eur J Cancer

Update on tumours of the adrenal cortex, phaeochromocytoma and extra-adrenal paraganglioma

Histopathology

Pathology and genetics: tumours of endocrine organs (IARC WHO classification of tumours)

Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines?

J Clin Endocrinol Metab

Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline

J Clin Endocrinol Metab

Mayo Clin Proc

Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996–2010

JAMA

The influence of population aging and size on the number of CT examinations in The Netherlands

Health Phys

Accuracy of plasma free metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review and meta-analysis

Endocr Pract

Diagnostic imaging over the last 50 years: research and development in medical imaging science and technology

Phys Med Biol

History and future technical innovation in positron emission tomography

J Med Imaging

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Ann Intern Med

Oxford centre for evidence-based medicine-levels of evidence

Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive

Cell Oncol

Primary spinal paragangliomas: a clinicopathological and immunohistochemical study of 30 cases

Histopathology

Original Article
Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review

Diagnostic imaging over the last 50 years: research and development in medical imaging science and technology