title: Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma.
abstract: BACKGROUND
  Pheochromocytomas can usually be confirmed or excluded using currently available biochemical tests of catecholamine excess. Follow-up tests are, nevertheless, often required to distinguish false-positive from true-positive results. The glucagon stimulation test represents one such test; its diagnostic utility is, however, unclear.
  
  
  OBJECTIVE
  The aim of the study was to determine the diagnostic power of the glucagon test to exclude or confirm pheochromocytoma.
  
  
  METHODS
  Glucagon stimulation tests were carried out at three specialist referral centers in 64 patients with pheochromocytoma, 38 patients in whom the tumor was excluded, and in a reference group of 36 healthy volunteers.
  
  
  METHODS
  Plasma concentrations of norepinephrine and epinephrine were measured before and after glucagon administration. Several absolute and relative test criteria were used for calculating diagnostic sensitivity and specificity. Expression of the glucagon receptor was examined in pheochromocytoma tumor tissue from a subset of patients.
  
  
  RESULTS
  Larger than 3-fold increases in plasma norepinephrine after glucagon strongly predicted the presence of a pheochromocytoma (100% specificity and positive predictive value). However, irrespective of the various criteria examined, glucagon-provoked increases in plasma catecholamines revealed the presence of the tumor in less than 50% of affected patients. Diagnostic sensitivity was particularly low in patients with pheochromocytomas due to von Hippel-Lindau syndrome. Tumors from these patients showed no significant expression of the glucagon receptor.
  
  
  CONCLUSIONS
  The glucagon stimulation test offers insufficient diagnostic sensitivity for reliable exclusion or confirmation of pheochromocytoma. Because of this and the risk of hypertensive complications, the test should be abandoned in routine clinical practice.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 8, 6525GA Nijmegen, The Netherlands. j.lenders@aig.umcn.nl
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: Thanh-Truc
authors.initials: TT
authors.lastname: Huynh
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D002395:Catecholamines / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D010912:Pituitary-Adrenal Function Tests / Q000379:methods*; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D002395:Catecholamines; D005934:Glucagon