Childhood-onset growth hormone deficiency (CO-GHD) is topical at present due to the increasing understanding of underlying genetic aetiologies, influence on childhood growth, and future effects on adolescence and adult health. There is no previous Irish data of this group of children.
Methods: A retrospective cohort study over 2 years (2013-2015) including all children diagnosed with GHD who received recombinant growth hormone treatment (rGH). Predictors of persistent GHD at final height were examined.
Results: A total of 43 children fulfilled inclusion criteria of which congenital GHD was identified in 37. Of these46% had structural pituitary abnormalities (n=15)/a novel genetic mutation of the POU1F1pituitary transcription factor (n=2), with a 2:1 male: female ratio. Idiopathic GHD was identified in 54% of children (n=20) which had a 9:1 male to female ratio. Acquired GHD due pituitary tumours were identified in six children with a 5:1 male to female ratio, and clinically presented with stunted growth, increased BMI and other pituitary hormone deficits. Median age at presentation in children with pituitary tumours was advanced (12.2 years - interquartile range 4.3) compared to children with congenital idiopathic GHD and GHD due to structural pituitary abnormalities; 7.6 and 3.7 years respectively. The assessment of children >14 years of age following rGH treatment revealed a mean gain in height SDS (Ht gain SDS) of 1.2±0.76 S.D. in the idiopathic group and positively correlated to the period of rGH treatment (P=0.016), however, children with structural/ genetic pituitary abnormalities had mean Ht gain SDS of 2.3±1.6 S.D. with a significant negative correlation to the Ht SDS at diagnosis (P<0.001). At final height, 4 of 7 adolescents retested for GHD (57%) exhibited persistent GHD. IGF-1 SDS after interruption of treatment <−2 S.D. correlated with GH status at transition (P=0.04). The underlying aetiology was a factor in prediction of GH status at final height, with complex pituitary defects more likely to be associated with persistent GHD (P=0.02).
Conclusions: This Irish study revealed novel characteristics such as higher male predominance in congenital idiopathic and acquired GHD due to pituitary tumours. A higher percentage of pathological congenital GHD was noted in this cohort compared to the literature. New insights on pituitary genetic mutations have emerged during the study, with future implications on the management of GHD at childhood and at the transition to adult care in the affected patients.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology