Sex-Related Differences in Self-Reported Symptoms at Diagnosis in Pheochromocytomas and Paragangliomas

Abstract

Context: Biological sex can play a role in the severity of certain diseases.

Objective: Our objective was to evaluate whether sex-related differences affect the signs and symptoms of pheochromocytomas and paragangliomas (PPGLs) at presentation.

Methods: We reviewed the records of patients with PPGLs at our center from 1995 to 2022.

Results: Our study included 385 patients with PPGLs: 118 (30.6%) head and neck paragangliomas (HNPGLs), 58 (15.1%) thoracoabdominal paragangliomas (TAPGLs) and 209 (54.3%) pheochromocytomas (PHEOs). The cohort consisted of 234 (60.8%) women and 151 (39.2%) men. At diagnosis, more women than men presented with headaches (47.5% vs 32.4%; P = .007); however, more men presented with diabetes (21.1% vs 12.5%; P = .039). When subdivided by tumor location, headaches occurred more often in women with HNPGLs and TAPGLs (31.0% vs 11.4%; P = .0499 and 60.0% vs 21.7%; P = .0167). More men presented with diabetes among patients with PHEOs (28.2% vs 11.2%; P = .0038). In regard to nonsecretory PPGLs, women presented with a higher prevalence of headaches (46.9% vs 3.6%; P = .0002), diaphoresis (16.3% vs 0.0%; P = .0454), and palpitations (22.4% vs 0.0%; P = .0057). In patients with secretory tumors, women presented with more headaches (58.9% vs 42.7%; P = .0282) and men with more diabetes (29.3% vs 12.5%; P = .0035).

Conclusion: In our cohort, more women presented with headaches across all tumor types and secretory statuses. More men presented with diabetes among patients with PHEOs and secretory tumors. In nonsecretory PPGLs, women had more adrenergic symptoms. These findings can be explained by differences in adrenergic receptor sensitivity, self-reported symptoms, and possibly other vasoactive peptides and sex-hormone status.

Keywords: biological sex-related differences; paragangliomas; pheochromocytoma.