# Seasonal and Climatic Influences on Catecholamine Metabolite Levels in Patients With and Without Pheochromocytoma–Paraganglioma

## TL;DR

This study found that non-PPGL patients show seasonal changes in catecholamine metabolites, while PPGL patients show less variation, suggesting environmental factors affect test results.

## Contribution

The study identifies seasonal and climatic influences on catecholamine metabolite levels in PPGL and non-PPGL patients.

## Key findings

- Non-PPGL patients had higher plasma metanephrine in autumn and winter.
- Temperature, daylight, and humidity were key predictors of metabolite levels in non-PPGL patients.
- PPGL patients showed no significant seasonal variation in metabolite levels.

## Abstract

Background/Objective: Pheochromocytomas and paragangliomas (PPGL) lead to marked catecholamine metabolite elevations, whereas the causes of mild increases remain unclear. We aimed to evaluate seasonal and climatic variation in plasma and urinary catecholamine metabolites in both PPGL and non-PPGL patients. Methods: We retrospectively reviewed adult patients who underwent plasma and/or 24 h urinary catecholamine metabolite testing at Ankara Bilkent City Hospital between February 2019 and May 2023. Using a big-data approach, we examined the relationship between catecholamine metabolite levels and monthly and seasonal climatic changes. Results: In non-PPGL patients, plasma metanephrine levels were significantly higher in autumn (p = 0.009) and winter (p = 0.027), and both plasma metanephrine (p < 0.001) and plasma normetanephrine (p = 0.003) showed transformed rank means in February that were elevated relative to the overall mean. Temperature, daylight duration, and humidity were the strongest predictors in the LASSO models. In contrast, catecholamine metabolite levels in the PPGL group showed no significant monthly or seasonal variation (all p > 0.05). However, when values exceeding the reference limits were examined, a significantly higher proportion of elevated plasma metanephrine measurements was observed during autumn (p = 0.005), whereas plasma normetanephrine elevations were most prominent during winter (p = 0.002). Conclusions: Catecholamine metabolite levels show notable variability in non-PPGL patients, which cannot be explained by seasonal comparisons alone. Monthly patterns and environmental factors—such as temperature, humidity, and photoperiod—should be considered when interpreting mild or borderline elevations to reduce false-positive results. In PPGL patients, seasonal variability was modest; however, plasma catecholamine metabolite testing showed higher diagnostic sensitivity during colder months.