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Alexander A Leung, Martin D Hyrcza, Janice L Pasieka, and Gregory A Kline

Objective: Exposure to high altitude may be a modifiable risk factor for pheochromocytoma and paraganglioma. The primary objective was to examine the association between the reported incidence of pheochromocytoma and paraganglioma across studies with differences in altitude.

Design: Meta-analysis with meta-regression.

Methods: The annual incidence proportion of pheochromocytoma and paraganglioma per 100,000 population was examined, accounting for differences in altitude. Meta-analysis using restricted maximum likelihood estimates with a random effects model was performed and meta-regression conducted to explore for heterogeneity.

Results: A total of 7 studies were identified from European, North American, and Asian countries. The pooled annual incidence proportion was 0.38 cases per 100,000 people (95% confidence interval [CI], 0.20 to 0.57 cases per 100,000 people) and this was associated with high amounts of statistical heterogeneity (P < 0.01; I2 = 97.5%). Meta-regression confirmed that altitude was significantly associated with the frequency of pheochromocytoma and paraganglioma. For every 500-meter increase in elevation, the annual incidence proportion increased by 0.31 cases per 100,000 people (95% CI, 0.01 to 0.61 cases per 100,000 people; P = 0.046). There were large amounts of residual statistical heterogeneity after meta-regression.

Conclusion: The incidence of pheochromocytoma and paraganglioma increased with altitude. However, variations between studies were only partially explained by elevation. Other factors, such as differences in study quality and the presence of clinical heterogeneity, likely impacted estimates of incidence.

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Alexander A Leung, Janice L Pasieka, Martin D Hyrcza, Danièle Pacaud, Yuan Dong, Jessica M Boyd, Hossein Sadrzadeh, and Gregory A Kline

Objective

Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data.

Design

Population-based cohort study in Alberta, Canada from 2012 to 2019.

Methods

Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated.

Results

A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60–79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algorithm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely approximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year.

Conslusion

The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.