ESPE Abstracts

Background: It has been previously proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Instead, amongst these, solely children with an identifiable monogenic cause of GHD or an identifiable functional or anatomical anomaly in the hypothalamic-pituitary axis should be considered GHD. The remaining patients should be defined as affected by “short stature unresponsive to stimulation tests” (SUS).

Methods: Retrospective analysis on 187 consecutive patients with short stature and pathological response to two stimulation tests for GH secretion, who underwent recombinant human GH (rhGH) therapy in a single Italian centre. Patients were divided into GHD (n=41, 22%; F=32%) and SUS (n=146, 78%; F=29%) groups, with a median follow-up (FU) time of 4.2 years (IQR 3.4-5.1). GH peaks at stimulation tests, height, bone age and serum levels of IGF-1 were compared at diagnosis, at 1 year of treatment and last available FU.

Results: At diagnosis, GHD and SUS populations did not differ significantly in age (11.8 vs 11.9, P=0.68), sex (F 32% vs 29%, P=0.78) and prevalence of short stature (height <-2 SDS) (100% vs 99%, P=0.45). IGF-1 SDS were significantly lower in GHD (-2.41 vs -1.99, P=0.02). The GH peak in the GHD group was lower when the stimulus was arginine (3.8 vs 5.0 ng/mL, P<0.01), but higher with insulin (3.5 vs 2.2 ng/mL, P=0.04). After 1 year of treatment, the prevalence of short stature was equally reduced in both groups (27% vs 25%, P=0.82), while the increase in IGF-1 SDS was greater in the GHD category (2.05 vs 1.52, P=0.01). At the last available FU, solely a minority of patients (52 of 187; 22% vs 29%, p 0.77) had reached the definitive height, none of which <-2 SDS. All 52 patients underwent retesting for GHD, which was positive in a significantly greater portion of GHD patients (33% vs 4%, P<0.01).

Conclusions: The GHD and SUS populations cannot be distinguished by GH stimulation tests alone. Both populations equally benefit from GH therapy in terms of stature. However, the stronger benefit of IGF-1 secretion in the GHD group suggests that deficient GH secretion may not be the sole cause of short stature in the SUS population. This is further corroborated by the finding that a vast majority of SUS patients do not have pathological retesting upon reaching definitive height.