Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging

Abstract

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. OBJECTIVE: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). DESIGN: Prospective study protocol, which has enrolled patients from 6 European centers with confirmed PPGLs. SETTING AND PATIENTS: Data were analyzed from 235 patients (37% iPPGLs, 36% sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. RESULTS: iPPGL patients were diagnosed at a significantly higher age than fPPGLs (p<0.001), found to have larger tumors (p=0.003) and higher metanephrine and normetanephrine levels at diagnosis (p=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs. 4.3 symptoms, p<0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than in fPPGL (60.9%) and sPPGL (21.5%). CONCLUSIONS: Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients the PPGL diagnosis had been delayed. Précis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.