Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that can affect the entire gastrointestinal tract. Although CD can develop at any age, many patients are diagnosed in childhood; specifically, ~20% of patients with CD develop IBD before the age of 20.

Cell surface amounts of GHR are the most important determinant of growth hormone (GH) responsiveness. In our patients, GHR mRNA levels were lower at diagnosis consistent with an inflammatory state, although this result was not statistically significant. One year later, when the disease was under control, the GHR values were found to have significantly increased, together with the IGF-I levels.

On the contrary, basal values of GHBP in CD patients were significantly lower compared to controls but they did not increase after 1 year of therapy. Therefore, our data show that GHBP level and GHR function are not closely correlated, as demonstrated also in other physiological and pathological conditions.

GHR regulation

GHR regulation and its cleavage to GHBP are tissue-specific. Therefore, it is possible that, in our patients, these mechanisms lead to an increase in GHR availability on the cell's surface, thus improving GH action.

To the best of our knowledge, there are no previous studies reporting GHR gene expression values in CD children at the onset of the disease and during follow-up. Our study raises the hypothesis of another cytokine interaction with the GH/IGF-I axis.

This mechanism involves the GHR before the start of signal transduction. Since GHR is present at growth plate level, it is possible of course that there is not only systemic but also local GH/IGF-I resistance.

However, in our study, only two patients showed severe growth retardation at diagnosis with a height under −2 SDS (9.5%) and this value is lower than the rate that has been previously reported. This is possibly due to the shorter interval between the onset of symptoms and diagnosis, due to improvements in diagnosis as shown also in the study of Song et al.

In the study, the median interval from onset of symptoms to diagnosis was 5.5 months, whereas the median diagnostic delay was 11.7 months in the previous study. Indeed, it has been shown that the duration of developmental delays and height in CD patients are significantly correlated, suggesting that earlier diagnosis might minimize and prevent growth retardation by reducing the duration of symptoms before treatment, and so rectifying the growth inhibiting effects of malnutrition and inflammatory cytokines.

The study has some limitations. Firstly, we acknowledge that the sample size was small, secondly the heterogeneity in drug treatments. Further studies with a larger sample size may provide more precise results.

Serum IGF and GHR gene expression levels change during therapy, per the clinical features, suggesting that disease activity modification is accompanied by variations in hypothalamic/pituitary-related factors. During disease remission, IGF-I and GHR mRNA expression increase, supporting the possibility of a strong correlation between growth factors, inflammatory process, and nutritional status.

These findings underline the importance of prompt control of inflammatory activity to prevent stunted growth and to promote good overall outcomes in mild to moderate CD. Furthermore, monitoring CD patients' growth is indispensable to assess their response to therapy over time.