Clinical and Biochemical Features of Pheochromocytoma Characteristic of Von Hippel-Lindau Syndrome

World J Surg. 2020 Feb;44(2):570-577. doi: 10.1007/s00268-019-05299-y.


Background: Approximately 30% of patients with apparent sporadic pheochromocytoma (Pheo) may later prove to have an inherited predisposition syndrome, most commonly Von Hippel-Lindau (VHL) disease. Our aim was to compare the clinical and biochemical features of Pheo in VHL to those in sporadic disease to identify differences that may be used to guide management and surveillance of Pheo in VHL patients.

Methods: Data of all patients who had adrenalectomy for histologic Pheo from 2000 to 2018 (QIIRB1749) were retrospectively reviewed. VHL patients were diagnosed by standard clinical criteria and/or genetic testing. Patients were classified as having sporadic Pheo (sPheo) if they had no family/personal history consistent with an associated genetic disorder and/or had negative testing for VHL, MAX, MEN1, NF1, RET and SDHAF2/B/C/D/A mutations.

Results: Of 175 patients, 38 (22%) had VHL and 137 (78%) had sPheo including 27 (20%) with negative genetic testing. Compared to sPheo, VHL Pheo patients were younger (mean 25.9 vs. 51.2 years, p < 0.001), less symptomatic (55% vs. 72%, p = 0.074), less hypertensive (46% vs. 64%, p = 0.043) and were more likely to have normal plasma metanephrines (85% vs. 25%, p < 0.001). VHL-related Pheos were smaller (median 2.8 cm vs. 4.4 cm, p < 0.001) but more often multifocal (>1 adrenal Pheo) (16% vs. 0%, p < 0.001). Recurrence >6 months from initial resection was common in VHL (40% vs. 0%, p < 0.001), median time to recurrence 15 years, (range 1-38 years).

Conclusions: Compared to those with sporadic Pheo, patients with VHL are more likely to be young, asymptomatic and normotensive and to have small, multifocal, normetanephrine-secreting tumors. Because recurrence is common in VHL and arises up to 38 years later, continued surveillance is advised.

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / etiology
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Pheochromocytoma / etiology
  • Pheochromocytoma / genetics*
  • Retrospective Studies
  • Young Adult
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / genetics*