Severity of short stature and not GH peak at diagnosis is the major determinant of growth response to GH therapy in short subjects without severe GH deficiency

A diagnosis of GH deficiency (GHD) is still considered the gold standard for GH therapy in many European countries. Aim of the present multicentre study was to retrospectively analyze growth response to GH therapy and factors related to good response of 2 groups of short subjects with different GH secretion. Inclusion criteria for both groups, besides short stature, were absence of puberty, no other diseases affecting height (Ht) and treatment to adult Ht with same GH therapy schedule (7 mg/m2/wk or 0.20-25 mg/kg/wk). Specific criteria for group 1 (n.76, 47 M and 29 F) was non severe GHD (peak 3-10 μg/L), whereas for group 2 (n.33, 21 M and 12 F) normal GH secretion (peak > 10 μg/L) with IGF-1 levels <-1 SDS responsive (50% increase) to IGF-1 generation test. Therapy duration was similar in the 2 groups: 77 mo in group 1 and 69 mo in group 2. At diagnosis (group 1 vs 2) Ht-SDS was different (-2.6± 0.8 vs -3.0±0.8; p=0.03), while age (9.7±2.5 yrs vs 9.2±2.5), target Ht-SDS (-1.3±0.8 vs -1.5±0.9), bone age delay (-2.0± 0.9 vs -2.3±1.0), IGF-1 SDS (-1.7±1.3 vs -2.2±1.1) were similar.There were no differences between males and females. The percentage of subjects with a Ht gain SDS <0.5 (15 vs 9%) and >1 SDS (63 vs 79%) was similar between the 2 groups. By examining the parameters affecting Ht gain, the subjects showed similar characteristics not associated to the group of treatment, i.e. significant negative correlation with statural deficit at diagnosis (r=-0.49; p=0.0001), age at diagnosis (r=-0.20; p=0.05) and positive with duration of therapy (r=0.28; p=0.007). GH peak at diagnosis was not related to Ht gain in both groups. In the whole group and in the 2 separate groups, among Ht SDS at diagnosis, age at diagnosis and therapy duration, multiple regression analysis identified Ht deficit at diagnosis as the only parameter influencing Ht gain (R2=0.42 in the whole group, R2=0.36 in group 1, R2=0.49 in group 2).Conclusions. Short subjects with normal GH secretion but low IGF-1 levels showed a similar growth response to GH therapy as short subjects with non severe GHD. In our subjects with short stature and different type of GH secretion, degree of short stature at diagnosis seemed the major determinant for height gain during treatment.