Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age

Summary Objective Bone marrow transplantation with total body irradiation ( BMT / TBI ) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH – IGF ‐ I axis in relation to adiposity. Design Cross‐sectional case control study. Patients BMT / TBI survivors ( n  = 22) and short stature control participants ( n  = 19), all GH ‐naïve or off GH treatment >3 months. Measurements Auxology, DEXA scans and GH – IGF ‐ I axis investigation: (i) 12‐h overnight GH profiles; (ii) insulin tolerance test ( ITT ); and (iii) IGF ‐ I generation test. Analysis: auto‐deconvolution of GH profile data and comparison of quantitative parameters using anova . Results Eighty‐two percent of BMT / TBI survivors had growth hormone deficiency ( GHD ) using ITT . GH profile area‐under‐the‐curve ( GH ‐ AUC ) was reduced in BMT / TBI survivors vs short stature control participants [geometric mean (range) 209 (21–825) vs 428 (64–1400) mcg/l/12 h, respectively, P  =   0·007]. GHD was more marked in those who had additional cranial irradiation ( CRT ) [ ITT peak 1·4 (0·2–3·0) vs TBI only 4·1 (1·1–14·8) mcg/l, P  = 0·036]. GHD was more marked at the end of growth in BMT / TBI survivors vs short stature control participants ( GH ‐ AUC 551 (64–2474) vs 1369 (192–4197) mcg/l/12 h, respectively, P  = 0·011) and more prevalent (9/11 vs 1/9, respectively, P  = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF ‐ I generation tests were normal. BMT / TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat‐adjusted mean difference for GH ‐ AUC 90·9 mcg/l/12 h, P  = 0·025). Conclusions GHD was more prevalent in BMT / TBI survivors than expected for the CRT dose in TBI , worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT / TBI .