# Symptomatic Pheochromocytoma: A Risk Model

## TL;DR

This study identifies factors that predict whether pheochromocytoma patients will be symptomatic and develops a tool to help clinicians assess risk and improve patient care.

## Contribution

A novel nomogram was developed to predict symptomatic pheochromocytoma based on sex, genetic status, and secretion profile.

## Key findings

- Approximately two-thirds of pheochromocytoma patients were symptomatic.
- Symptomatic patients had higher rates of intraoperative and postoperative complications.
- A nomogram incorporating sex, genetic status, and secretion profile showed moderate discrimination (AUC 0.799).

## Abstract

Pheochromocytoma is increasingly detected incidentally or through genetic screening, resulting in a growing proportion of patients without typical symptoms. We retrospectively studied 173 patients diagnosed and/or operated on for pheochromocytoma at a tertiary hospital between 1984 and 2021 to identify factors associated with symptomatic presentation and to compare perioperative outcomes. Approximately two-thirds of patients were symptomatic. Female sex, sporadic disease (negative genetic testing), and a noradrenergic secretion profile were independently associated with symptomatic presentation. Symptomatic patients experienced higher rates of intraoperative and postoperative complications. We also developed a nomogram based on sex, genetic status, and secretion profile to estimate an individual patient’s probability of being symptomatic, showing moderate discriminatory ability. This tool may assist clinicians in identifying higher-risk patients and optimizing preoperative evaluation and perioperative monitoring.

Background/Objectives: Pheochromocytoma (PHEO) is increasingly detected incidentally or through genetic screening; however, predictors of symptomatic presentation and its perioperative impact remain unclear. We aimed to quantify the prevalence of symptomatic PHEO, identify associated factors, compare perioperative outcomes, and develop a predictive nomogram. Methods: We retrospectively analyzed patients diagnosed and/or operated on for PHEO at a tertiary referral center between 1984 and 2021. Associations with symptomatic presentation were assessed using univariate and multivariable logistic regression analyses. A nomogram was constructed based on independent predictors and evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Results: Among 173 patients (mean age 44.4 ± 15.8 years; 53.2% women), 67.1% were symptomatic. In multivariable analysis, male sex (odds ratio [OR] 0.33; p = 0.023) and the presence of a germline mutation (OR 0.15; p = 0.004) were associated with a lower likelihood of symptoms, whereas a noradrenergic secretion profile was associated with a higher likelihood (OR 12.73; p = 0.02). Symptomatic patients had higher rates of intraoperative (OR 2.60; p = 0.032) and postoperative complications (OR 3.09; p = 0.04). The nomogram incorporating sex, genetic status, and noradrenergic profile demonstrated moderate discrimination (AUC 0.799; 95% confidence interval 0.722–0.877; p < 0.001). Conclusions: Symptomatic PHEO is associated with sex, genetic status, and noradrenergic secretion profile and is linked to increased perioperative morbidity. A simple nomogram based on readily available variables may help estimate individual risk and support perioperative management.