ESPE Abstracts

Introduction and Aim of the Study: girls with previous pediatric medulloblastoma (MB) are at risk of short stature and impairment of the hypothalamic pituitary gonadal function due to multiple risk factors;our aim was to assess the impact of hypergonadotropic hypogonadism (HH) on growth up to final height (FH) in females with or without growth hormone deficiency (GHD).

Methods: anthropometrics (height-Ht-SDS, BMI-SDS, Tanner stage, distance from target height- ∆TH) and biochemical data (LH, FSH, estradiol) of 30 females diagnosed with MB at the age of 6.7±3.3 years (at least 10 years old at last visit) were retrospectively collected at relevant time-points: first endocrine visit-T0 (9.2±3.9yrs);at suspected biochemical pubertal start-PS (defined as detectable serum LH/estradiol, n=16/30,8.1±1.4yrs);at Tanner B2 (n=25/30,10.9±1.3yrs);at GHD diagnosis (n=21/30,11.0±2.4yrs), six months after Tanner B2 (n=16/30,11.7±1.2yrs), at HH diagnosis (n=12/30,13.5±1.4yrs) and at FH (n=21/30,15.4±1.6yrs;16/21 with GHD). GHD patients were treated with rhGH therapy. Eleven girls underwent the standard risk, n=19 the high risk protocol and n=26 craniospinal-radiotherapy (CSRT 32.3±8.3 Gy). HH was defined as Tanner-B1 at 13 yrs (n=4) or as arrested pubertal progression for 12 months (n=8).

Results: There were no differences in cancer risk grading, RTCS dose and GHD (yes/no) between HH and non-HH females. HH and non-HH females presented a progressive height decline independently of GHD (T0 -0.9±1.2 vs -0.6±1.2 SDS;Tanner B2 -1.1±1.0 vs -0.7±1.0 SDS, respectively) with HH girls showing a steeper decrease of stature at HH diagnosis (-1.8±1.3 SDS), an absent catch-up after estrogen-replacement (ERT) compared to non-HH girls at FH (-1.8±1.0 vs -1.0±1.2 SDS) and a reduced final ∆TH (-1.6±0.7 vs -1.0±1.2 SDS);FSH values were elevated in HH compared to non-HH females at T0 (53.1±40.4 vs 11.4±16.0 IU/l, P=0.003), at Tanner B2 (54.9±47.1 vs 18.0±17.9 IU/l, P=0.02), after six months PS (73.9±38.7 range 33.7-114.1 vs 20.1±16.6 IU/l range 6.5-54.3, P=0.009). HH was predicted by FSH values at T0 in logistic regression analyses (R2 0.291, P=0.02), while FH by height (β 0.87, P<0.0001) and Tanner stage (β 0.32, P=0.02) at T0 in multiple regression analyses (R2 0.598).

Conclusions: the study shows that height is impaired in females with childhood-onset MB and HH;high FSH values are predictive of future HH before the age of 10 years even when spontaneous puberty occurs. ERT started an earlier age could improve height outcome.