Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD) subjects: the role of timing of onset of GHD.

Abstract

IGF-I standard deviation score (SDS) is widely used in clinical practice; however, factors determining IGF-I SDS in GH-deficient (GHD) individuals remain incompletely understood. Earlier studies have been limited by the small size of cohorts studied. We have used the KIMS database to examine if a true difference exists between subjects who developed GHD in adult life (AO), and those who developed GHD in childhood (CO). A total of 1317 patients fulfilled the inclusion criteria, 1073 with AO GHD and 244 with CO GHD. Serum IGF-I concentrations were determined by a hydrochloric acid-ethanol extraction radioimmunoassay method using synthetic IGF-I for labelling. The reference range was calculated using normative data from healthy Swedish individuals. A total of 86% of patients with CO GHD but only 52% of patients with AO GHD had IGF-I SDS below -2 SDS. The CO cohort had a lower IGF-I SDS (-4.69 vs. -2.24, P < 0.0001), a smaller body mass index (BMI; 26.6 vs. 28.6 kg/m2, P < 0.0001) and waist-hip ratio (WHR; 0.90 vs. 0.92 P < 0.001) than the AO cohort. A stepwise multiple linear regression was performed to examine the principal determinants of IGF-I SDS. Age at onset of GHD was the most important determinant of IGF-I SDS, contributing 17% towards the variability of IGF-I SDS. Timing of onset, gender, BMI, and number of pituitary hormone deficiencies other than GH deficiency were also significant determinants of IGF-I SDS. Whilst age at onset of GHD was the most important determinant of IGF-I SDS, individuals with CO GHD had values on average 1.43 lower than those with AO GHD, all other factors being equal. Potential explanations include differences in GH secretory patterns, variation in body composition, and/or suboptimal treatment of GHD in childhood.