Three-decade investigation of familial pheochromocytoma. An allele of von Hippel-Lindau disease?

Arch Intern Med. 1993 Nov 22;153(22):2550-6.


Background: Usually sporadic, pheochromocytoma can, on occasion, complicate genetic disorders, such as neurofibromatosis 1, von Hippel-Lindau disease, and multiple endocrine neoplasia 2; some families seem to have just pheochromocytoma, where it may have occurred by chance. The natural history of a large kindred believed to have an excess of pheochromocytoma 34 years ago was followed with the hypothesis that the predisposition was, in fact, present and that family education and surveillance would decrease mortality.

Methods: Prospective observation and diagnostic surveillance for pheochromocytoma were conducted on the inception cohort, defined as three branches of the kindred in 1960. Of 619 descendants of three (of 11) siblings of German origin, 333 were evaluated in person at least once in the three decades of surveillance. No pheochromocytomas were known to have occurred in the eight other branches. A total of 522 persons from the 11 branches were evaluated.

Results: Five of the eight initial patients with pheochromocytoma died of cardiovascular complications attributable to the tumor. In follow-up, eight additional relatives were newly diagnosed with pheochromocytomas (at an average age of 19 years), and others had additional or recurrent pheochromocytomas, meningioma, para-adrenal paraganglioma, and a functioning glomus vagale; none died.

Conclusions: A continuing excess of pheochromocytoma seems present in the family. Whether the incompletely penetrant gene in this family is allelic to the von Hippel-Lindau gene on chromosome 3 or is a distinct locus remains to be resolved with molecular studies. Meanwhile, education and surveillance seem to decrease mortality from pheochromocytoma in this family.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Alleles*
  • Child
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Pheochromocytoma / complications
  • Pheochromocytoma / genetics*
  • Prospective Studies
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / genetics*