Pheochromocytoma in Children and Adolescents With Multiple Endocrine Neoplasia Type 2B

J Clin Endocrinol Metab. 2019 Jan 1;104(1):7-12. doi: 10.1210/jc.2018-00705.

Abstract

Context: Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early-onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of pheochromocytoma (PHEO) development. The literature on PHEO in patients with MEN2B is limited with most data being reported from adult studies that primarily address MEN2A.

Objective: The aim of the current study is to describe PHEO development in a cohort of pediatric patients with MEN2B.

Design: Retrospective chart review of patients with MEN2B evaluated at the National Institutes of Health in the period between July 2007 and February 2018.

Results: A total of 38 patients were identified (21 males and 17 females). Mean age at MEN2B diagnosis was 10.6 ± 3.9 years. Eight patients (21%) developed PHEO in the course of follow-up to date, all of whom were sporadic cases with the classic M918T RET mutation. PHEO was diagnosed based on biochemical and/or imaging screening studies in five patients, whereas three patients presented with symptoms of excess catecholamines. PHEO was diagnosed at a mean age 15.2 ± 4.6 (range, 10 to 25) years and 4.0 ± 3.3 years after MEN2B diagnosis. Only one patient was diagnosed with PHEO as the initial manifestation of MEN2B after she presented with hypertension and secondary amenorrhea.

Conclusion: Undiagnosed PHEO can be associated with substantial morbidity. Current American Thyroid Association guidelines recommend PHEO screening starting at age 11 for the high-/highest risk group. The youngest patient diagnosed with PHEO in our cohort was an asymptomatic 10-year-old, suggesting that PHEO development may begin before the screening-recommended age of 11, though remains clinically undetectable and thus the current screening guidelines seem appropriate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / diagnosis
  • Adrenal Gland Neoplasms / etiology*
  • Adrenal Gland Neoplasms / mortality
  • Adult
  • Age of Onset
  • Catecholamines / metabolism
  • Child
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Mass Screening
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2b / complications*
  • Multiple Endocrine Neoplasia Type 2b / genetics
  • Multiple Endocrine Neoplasia Type 2b / mortality
  • Pheochromocytoma / diagnosis
  • Pheochromocytoma / etiology*
  • Pheochromocytoma / mortality
  • Retrospective Studies
  • Young Adult

Substances

  • Catecholamines