Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma.
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.
Lenders
Jacques W M
JW
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
Pacak
Karel
K
Huynh
Thanh-Truc
TT
Sharabi
Yehonatan
Y
Mannelli
Massimo
M
Bratslavsky
Gennady
G
Goldstein
David S
DS
Bornstein
Stefan R
SR
Eisenhofer
Graeme
G
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
D002395:Catecholamines; D005934:Glucagon