Background: Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases. Methods: A retrospective analysis of 136 patients in a tertiary hospital (1984–2021). Epidemiological, clinical, and histological variables were analysed. Statistics: SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. p < 0.05 was considered statistically significant. Results: 64.71% of the cases (n = 88) presented a genetic mutation (familial cases). Additionally, 32.39% (n = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89–0.97)), blood pressure-related symptoms (OR = 0.22 (0.06–0.89)), bilaterality (OR = 15.49 (3.76–63.84)), and size (OR = 0.70 (0.54–0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24–144.34)). Conclusions: Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.

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.