To our knowledge, this is the first study that administered the EQ-5D questionnaire to Italian GHD children. In our study, the mean EQ-5D utility value was 0.95 (SD 0.09), while the mean EQ VAS score was 86.2 (SD 14.2). Although no reference data are available for healthy subjects under the age of 18, our values were not dissimilar to those of the study by Szende et al. [10] for the group of healthy subjects aged 18–24 with the mean EQ VAS (self-assessed health) score of 87.5 [standard error (SE) 0.06], and the mean utility value of 0.985 (SE 0.003). However, in our study the proportion of respondents who indicated problems in the 5 dimensions of the EQ-5D was higher than that of healthy individuals aged 18–24 in the reference group reported by Szende et al. [10]: mobility: 7.7% vs 1.0%; self-care: 5.6% vs 0.7%; usual activities: 9.9% vs 1.8%; pain/discomfort: 16.9% vs 8.6%; anxiety/depression: 11.3% vs 5.2%. We note that the comparison group of healthy subjects aged 18–24 should be considered a proxy, and could differ to our sample in some respects, in particular compared to the younger boys and girls. Thus, the comparison with our results should be interpreted with caution.

Regarding subgroup analyses, we found that 4–7 years old boys were more likely to have some problems in self-care and usual activities than older children or adolescents. Nevertheless, these differences could be also due to the limited sample size of this age group, including only 7 boys. In our study, females aged 13–18, were more likely to have problems than males of the same age in the mobility (14% vs 2%), self-care (7% vs 0%), and anxiety or depression (29% vs 7%). However, the results also in this case should be interpreted with caution given the limited number of 14 females. Basically, the overall generic HRQoL of our study population can be considered high, and in line with the international reference values.

As for disease-specific HRQoL measured in children and adolescents through the QoLISSY-child version, in the overall study population we found a significantly higher score than the reference value for the physical domain (78.66 vs 73.69), and lower scores for coping (42.65 vs 55.60) and treatment (48.88 vs 55.12). Instead, when we compared our results to the reference values specific for GHD patients (not considering ISS patients), our mean scores were significantly lower for all domains, except physical.

As for disease-specific HRQoL measured in parents through the QoLISSY-parent version, in the overall study population we found a significantly higher score than the reference value for the physical domain (78.40 vs 71.80), and a lower score for treatment (48.29 vs 55.18). Comparing our results with those of parents of GHD patients only (excluding parents of ISS patients), our mean scores were significantly lower for social, emotional, treatment, effect on parents, and total score domains.

Comparing our results with those from a field test which describes the validation of the QoLISSY in Italy [7], we did not find significant differences. In the QoLISSY-child version (sample: 24 children) our means were: not significantly higher for physical (78.66 vs 70.83 of the QoLISSY Italian validation study; p = 0.07), social (74.10 vs 67.06, p = 0.17), emotional (71.14 vs 63.80; p = 0.09), beliefs (68.84 vs 63.28; p = 0.33), and total score (74.27 vs 67.23; p = 0.09); they were very similar for coping (42.65 vs 43.26; p = 0.91) and treatment (48.88 vs 48.66; p = 0.96). In the parent version (sample: 32 parents), our means were: not significantly higher for social (71.68 vs 67.83; p = 0.41), beliefs (66.81 vs 63.54; p = 0.55), effects on parent (62.15 vs 58.21; p = 0.40); very similar for physical (78.40 vs 78.78; p = 0.92), emotional (68.57 vs 67.22; p = 0.75), future (79.44 vs 78.39; p = 0.82) and total score (72.38 vs 71.36; p = 0.80); and not significantly lower for coping (42.98 vs 46.70; p = 0.42).

The systematic review by Backeljauw et al. [4] included five studies [11,12,13,14,15] comparing QoL between children with short stature due to GHD or ISS and children with normal stature; four of these studies [12,13,14,15] reported evidence of lower scores in children with short stature than normal stature children, while one study [11] found no difference. None of these studies used the EQ-5D or the QoLISSY questionnaires.

The review included also nine studies comparing QoL between short stature subgroups [14, 16,17,18,19,20,21,22,23]. Five out of 9 studies [14, 16, 19, 20, 23] did not find significant differences in QoL based on different causes of short stature or treatment status; considering only those studies using QoLISSY in GHD children, Bloemeke et al. [16] reported a mean QoLISSY total score after 12 months of treatment of 61.60 (SD 22.88), that is lower than the mean total score of our study (72.38), while Quitmann et al. [19] reported a mean QoLISSY total score after 12 months of treatment of 53.61 (SD 24.39), also in this case lower than the mean total score of our study.

Two out of nine studies [17, 18] found that QoL was significantly higher in children with less severe short stature than in children with more severe short stature. Bullinger et al. [17] reported a mean QoLISSY total score in GHD or ISS children of 73.10 (SD 21.39), similar to our mean total score (72.38). Drosatou et al. [18] reported a mean QoLISSY total score in GHD or ISS children according to the short stature level: height SDS ≤ − 2.0, 75.37 (SD 13.45); height SDS > − 2.0, 79.81 (SD 13.27). The first score (SDS ≤ − 2.0) was similar to our result.

Sommer et al. [22] reported that children with ISS had better QoL than SGA children with short stature. The study by Silva et al. [21] did not find differences between ISS and GHD children, while the treated children had significantly better HRQoL on the QoLISSY-child—physical domain compared to untreated ones; the mean QoLISSY physical score at baseline was 80.91 (20.16), similar to our mean physical score (78.40).

The only Italian study included in the review of Backeljauw [4] was the conference proceeding by Bettini et al. [5]. This study used the QoLISSY questionnaires (child and parent versions) in 80 GHD children and their parents, reporting a total QoL (defined as “satisfying QoL score”) for children of 85.7%, and of 60% for parents; however, it is not clear how these percentages have been calculated and therefore we cannot compare these results with ours.

Two recent conference abstracts [24, 25] describe the quality of life of children treated with once-weekly LAGH compared to those treated with daily GH and that of their parents. The QoLISSY core module was administered to girls aged 3–11 years and boys aged 3–12 years, and to their parents in eight countries. After 12 months of treatment, the total score for QoLISSY-Child was 74.69 in the LAGH group vs 69.03 in the daiòy GH group. These scores were similar to that in our study (74.27); however, the results are not fully comparable due to the different population ages (3–11/12 vs 4–18 of our study). Parents showed lower total scores than their children (69.49 in the LAGH group vs 63.80 in the daily GH group).