title: Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma.
abstract: OBJECTIVE
  Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation.
  
  
  METHODS
  Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated (sporadic group).
  
  
  RESULTS
  A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median of 34.5 months without morbidity. Median tumor doubling time was 17 months.
  
  
  CONCLUSIONS
  Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and less functional than sporadic pheochromocytomas.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Walther
authors.forename: R
authors.initials: R
authors.lastname: Reiter
authors.forename: H R
authors.initials: HR
authors.lastname: Keiser
authors.forename: P L
authors.initials: PL
authors.lastname: Choyke
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: K
authors.initials: K
authors.lastname: Hurley
authors.forename: J R
authors.initials: JR
authors.lastname: Gnarra
authors.forename: J C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: G M
authors.initials: GM
authors.lastname: Glenn
authors.forename: B
authors.initials: B
authors.lastname: Zbar
authors.forename: W M
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010673:Pheochromocytoma / Q000150:complications* / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000235:genetics*