title: Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas.
abstract: BACKGROUND
  Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening.
  
  
  OBJECTIVE
  The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL.
  
  
  METHODS
  The study design was retrospective descriptive.
  
  
  METHODS
  PATIENTS included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL.
  
  
  METHODS
  There was no intervention.
  
  
  METHODS
  Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured.
  
  
  RESULTS
  Mean +/- sd age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified.
  
  
  CONCLUSIONS
  SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.
authors.affiliation: Section on Medical Neuroendocrinology, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, 10 Center Drive, Building 10, CRC, Room 1-E 3140, MSC 1109, Bethesda, Maryland 20892-1109, USA.
authors.forename: Henri J L M
authors.initials: HJ
authors.lastname: Timmers
authors.forename: Anna
authors.initials: A
authors.lastname: Kozupa
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Margarita
authors.initials: M
authors.lastname: Raygada
authors.forename: Karen T
authors.initials: KT
authors.lastname: Adams
authors.forename: Daniel
authors.initials: D
authors.lastname: Solis
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D007506:Iron-Sulfur Proteins; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase