GH-IGF1 Axis in Children with Cystic Fibrosis

Objective To verify whether growth hormone receptor gene expression plays a role in Cystic fibrosis (CF)children’s growth, as a consequence of the chronic inflammatory condition and malnutrition.

Design We enrolled forty-nine prepubertal patients (24 males and 25 females) affected by CF in a stable clinical condition, 19 of whom had been diagnosed through newborn screening and 30 following presentation of symptoms. Patients had no significant comorbidity affecting growth or CFTR (Cystic Fibrosis Transmembrane conductance Regulator)-related diabetes requiring insulin therapy. Blood was collected during two follow-up visits to measure IGF-I, GHBP and GH-R gene expression. Fifty-two healthy children, sex- and age-matched, were recruited as a control group.

Methods In this study we compared BMI, height, weight, IGF-I, GHBP and GHR gene expression values (evaluated by Chemiluminescent Immunometric assay; ELISA and Real time PCR respectively) in CF patients diagnosed through NBS (New born screening), or by symptoms (Late Diagnosis (LD)) and in healthy controls.

Results BMI increased significantly in patients between the time of diagnosis and check-ups (p<0.001) and particularly in the LD group, the median value was lower at diagnosis and significantly higher (p<0.001) at follow up visits compared to controls. At the initial evaluation, higher levels of IGF-I (not statistically significant) were found in both the NBS group and in the LD group compared to the control group. At the second evaluation, significantly higher levels of IGF-I (p=0.003) were found in both the NBS and LD groups compared to controls; GHR mRNA expression had significantly increased (p=0.013) in LD patients in comparison with the first evaluation and was significantly higher in the NBS and LD groups than in controls. GHBP values had significantly increased (p=0.047) in the NBS group after one year of therapy compared to first visit levels and were significantly higher (p<0,0001) in the NBS and LD groups compared to controls.

Conclusion In our LD patients during childhood, we observed good auxological values and a GH/IGF-I axis function within normal range for the factor evaluated. However, earlier diagnosis through NBS might further minimize and prevent growth retardation, by reducing the duration of symptoms before treatment.