medwireNews: Years of treatment with recombinant human growth hormone (rhGH) does not increase the cumulative lifetime exposure to insulin-like growth factor (IGF)-1 above the population average in children born small for gestational age (SGA), a study shows.
The researchers note that epidemiological studies have linked high IGF-1 levels to “an increased risk of several common cancers.”
Their analysis used data from 6459 participants in three longitudinal and four cross-sectional population-based cohorts in the Copenhagen area of Denmark to calculate the estimated cumulative exposure to IGF-1 between the ages of 0 and 76 years.
“We believe that cumulative lifetime exposure to IGF-I rather than intermittent changes in IGF-I levels is the predictor of disease risk”, they explain.
“This seems plausible from a physiological perspective as carcinogenesis requires accumulation of genetic damage.”
The team found that people “predominantly” remained within the same tertile of IGF-1 standard deviation score (SDS) throughout their life, with intraclass correlation coefficients of 0.50 in male participants and 0.53 for females.
A value of 0.50 or greater is regarded as showing good reliability for a blood biomarker, say Anna Sophie Lebech Kjaer (Copenhagen University Hospital – Rigshospitalet, Denmark) and study co-authors.
“Thus, a single measurement of IGF-I (SDS) is a reliable approximation of cumulative lifetime exposure”, they write in The Journal of Clinical Endocrinology & Metabolism.
In a subpopulation of 167 people with the largest number of consecutive measurements, 59% changed IGF-1 SDS tertile at some point, but only 9% had a large change from the first to third tertile or vice versa.
Using these population data as a reference, the team found that rhGH treatment for a median of 9.4 years in nine patients born SGA increased their average estimated lifetime exposure to IGF-1 from 9512 to 11,271 µg/L.
However, this was significantly lower than the average in the reference population, of 12,648 µg/L. The increase associated with rhGH treatment corresponded to an increase in IGF-1 SDS from –0.89 to –0.35.
“It is reassuring that years of GH-induced increased IGF-I levels do not seem to impact the lifetime IGF-I exposure in a substantial way”, say the researchers.
“We speculate that this is in part why GH therapy does not seem to increase cancer incidence in children without additional risk factors.”
In the reference population, the pubertal peak in IGF-1 occurred earlier in girls than boys, at a median of 14.6 years and Tanner stage 4 in the former and 15.1 years and Tanner stage 5 in the latter. Levels declined throughout adult life, but slightly more rapidly in women than men. Higher BMI was associated with higher IGF-1 levels in childhood, but with lower levels in adulthood.
By Eleanor McDermid
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