Pegvisomant-primed glucagon stimulation test in assessing GH  reserve and GH/IGF kinetics in adults suspected of GH deficiency.
OBJECTIVE
The accuracy of the glucagon stimulation test(GST) in diagnosing adult GH deficiency (GHD) has recently been questioned. Because pegvisomant (PegV)increases endogenous GH secretion, we hypothesized that priming PegV to the GST (PegV-GST) 72 h beforehand would improve the diagnostic accuracy of this test. This pilot study aimed to prospectively compare PegV-GST to two other diagnostic tests for adult GHD.


METHODS
Adults suspected of GHD underwent PegVGST,GST and insulin tolerance test (ITT) in random order.Growth hormone levels (measured by a PegV insensitive assay) during PegV-GST, GST and ITT were compared,and acute effects of PegV on GH/IGF kinetics were assessed.


RESULTS
Ten subjects with hypothalamic-pituitary disease and 1–4 pituitary hormone deficiencies were studied. Basal and peak GH levels with the PegV-GST were comparable to those of the GST and ITT. The five subjects that failed the GST and ITT were the same subjects that failed the PegVGST,using the peak GH cut point of<3 ng/mL for this test. After PegV priming, basal GH and GH binding protein(GHBP) increased (both P<0.01) and total IGF-I and bioactive IGF decreased (both P<0.05), whereas IGF-II and IGFBPs -1, -2 and -3 were unchanged compared to pre-PegV priming. Serum PegV levels correlated positively with basal GH, peak GH, IGFBP-1 and IGFBP-2 levels, and negatively with D bioactive IGF and DGHBP (all P<0.05).


CONCLUSIONS
Single dose PegV administration in adults suspected of GHD increased basal GH and GHBP, with concomitant rapid fall in IGF-I levels and bioactive IGF. PegV priming did not appear to improve the diagnostic accuracy of the GST. Further studies involving larger subject numbers are needed to verify the clinical utility of PegV-GST in evaluating adult GHD.
Kevin C J
KC
Yuen
Jan
J
Frystyk
Sharon A
SA
Rhoads
Martin
M
Bidlingmaier
D000328:Adult; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007018:Hypopituitarism / Q000175:diagnosis* / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies
D018970:Insulin-Like Growth Factor Binding Protein 1; D019382:Human Growth Hormone; D005934:Glucagon; C406545:pegvisomant