Abstract
AJ Varewijck, SW Lamberts, SJ Neggers, LJ Hofland, JA Janssen J Clin Endocrinol Metab 7 January 2013 [Epub ahead of print]
Growth hormone (GH) replacement is recommended for adults with severe growth hormone deficiency (GHD) and impaired quality of life (QOL). Total insulin-like growth factor 1 (IGF-1) concentration is used to monitor and titrate GH therapy, but does not correlate well with QOL. This may reflect the fact that immunoassay measurements of circulating IGF-1 do not take into account the modifying effects of IGF binding proteins. Measurement of IGF-1 bioactivity using a kinase receptor activation (KIRA) bioassay may reflect the clinical effects of GH replacement more accurately.
This study examined the relationship between QOL and total IGF-1 or IGF-1 bioactivity during GH treatment. Patients (n = 106) with GHD were assessed at baseline, six months and 12 months using a GHD-specific QOL module and a generic health survey. Total and bioactive IGF-1 were measured at all time points and adjusted for age.
Consistent with previous studies, fewer patients had pretreatment IGF-1 bioactivity within the normal range (22%) than had total IGF-1 within range (38%). Both total and bioactive IGF-1 were significantly increased after 12 months of treatment, although only 50% of patients had IGF-1 bioactivity in the normal range, compared with 81% for total IGF-1.
QOL did not significantly improve after 12 months, possibly due to a high baseline – many of these patients were not GH-naive and had been off treatment for just one month before the study. Pretreatment, QOL was not correlated with either total IGF-1 or IGF-1 bioactivity. At 12 months, there was some tendency towards higher QOL scores, as measured by the GHD-specific module, with higher IGF-1 bioactivity (correlation r = 0.28, P = 0.01), a relationship not seen with total IGF-1.
The authors conclude that IGF-1 bioactivity may be an improved marker for some aspects of QOL. An interesting follow-up study would be to assess the use of IGF-1 bioactivity for GH dose titration.