Changes in body composition in male adolescents with childhood-onset GH deficiency during transition.

OBJECTIVE: Restarting rhGH in adolescents with childhood-onset (CO-) GHD is usually based on GH retest, IGF-1, additional pituitary hormone deficiencies, pituitary morphology and history. Short-term changes in body composition in adolescents with CO-GHD when off rhGH may contribute to the identification of those in need of treatment continuation. DESIGN: This is a longitudinal single-centre study. PATIENTS AND MEASUREMENTS: The body composition of 90 male adolescents with low-likelihood severe GHD of adolescence was measured by DXA at the time of rhGH discontinuation and 6 months thereafter. At diagnosis, mean age was 5.4 years, height was -2.68 SDS and stimulated GH peak was 5.1 ng/mL. RhGH treatment was stopped at 16.7 years at near-final height of -0.44 SDS. The adolescents were re-examined after 3 months off rhGH using both IGF-1 and GHRH-arginine tests. Severe GHD of adolescence was defined both by stimulated GH < 16 ng/mL and by IGF-1 < -1.90 SDS. RESULTS: Males with severe GHD of adolescence (n = 8) gained more relative and absolute fat mass and lost significantly more relative lean body mass after 6 months off rhGH than healthy individuals (n = 82; P < 0.001). The sum of absolute fat mass gain and lean body mass loss (=body composition changes score; BCC score) correlated highly with the GH peak (R = 0.17; P < 0.001). A BCC score >7.0 kg was 88% sensitive and 94% specific for detecting severe GHD of adolescence (AUC = 0.975). CONCLUSIONS: Short-term body composition changes when off rhGH are good clinical markers of severe GHD in male adolescents. The novel BBC score is an aggregate of these changes.

Stable bone density in adolescents with severe growth hormone deficiency after six months off rhGH.

OBJECTIVE: Severe growth hormone deficiency causes lean body mass loss in male adolescents and increased fat mass in both sexes. The changes appear after a 6 month GH pause. AIM: The aim was to examine bone density and structure changes in adolescents with severe GHD during a 6-month rhGH treatment interruption. PATIENTS AND METHODS: In total, 113 adolescents (20 females) paused rhGH treatment for 6 months at near-final height, and they were retested with arginine-GHRH challenge and basal IGF-1. Severe GHD was diagnosed in 19 individuals (5 females, GH peak <16 ng/ml and IGF-1 < -1.9 SDS) and excluded in 94 (15 females). Bone density and structure were measured by pQCT of the forearm and DXA of the total body at cessation of rhGH and 6 months later. RESULTS: In severe adolescent GHD (sGHD) patients, trabecular density (mg/cm3) decreased from 214 to 202 (p < 0.01); changes in the adolescents with normal test results (tGHD) were from 221 to 214 (p < 0.05). Cortical density (mg/cm3) increased from 1077 to 1099 (p < 0.01) in sGHD patients and from 1060 to 1082 in tGHD patients (p < 0.001). The strength strain index (mm3) showed no significant changes in sGHD patients (306 to 307) but changed from 302 to 315 in tGHD patients (p < 0.05). Total bone area (mm2) shifted from 145.1 to 145.2 in sGHD patients and from 153 to 156 in tGHD patients. Total body aBMD (g/cm2) increased in both groups: from 1.10 to 1.12 in sGHD patients and from 1.11 to 1.14 in tGHD patients (p < 0.01). All bone measurements remained within the reference ranges, and there were no differences between sGHD and tGHD patients. CONCLUSION: During a 6-month pause of rhGH treatment, the bone structure and density of adolescents with sGHD did not show changes implying harm. Routine retesting of adolescents, including 6 months without GH, is unlikely to be detrimental to the bone.