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.
15 Sep 2022 - 17 Sep 2022