Revaluation of the clinical and metabolic behavior of GHD children during GH treatment according to newly proposed note 39 of the Italian Medicines Agency (AIFA)

Background The newly proposed note 39 of the Italian Medicines Agency (AIFA) revisited the diagnostic criteria of growth hormone deficiency (GHD) in children and, applying it, a percentage of children previously diagnosed as GHD may have received a wrong diagnosis and a unnecessary treatment, with potential clinical implications. Aim To evaluate the clinical and metabolic behavior of GH-treated children according to the new criteria of GHD diagnosis. Subjects and Methods: We retrospectively analyzed clinical and metabolic data of 310 prepubertal children (220 M, 90 F, age 10.8 ± 2.9 yrs) with short stature admitted to our section of Endocrinology during the years 2005-2014, having at least a 24 months follow-up. All children were divided, according to new AIFA note 39, into group A (n°181 with a peak of GH < 8 ng/dl after 2 tests), group B (n°103 with a peak of GH ≥ 8 and < 10 ng/dl) and group C (n°26 with a peak of GH > 10 ng/dl). Results At baseline, group A showed higher waist circumference than B (p=0.031) and C (p=0.041), while no difference in metabolic parameters was found between the 3 groups. As expected, group C showed a better height (-1.70 ± 0.35 SD) than A (-2.04 ± 0.72; p=0.002) and B (-2.06 ± 0.86; p=0.010), associated with higher bone/chronological age ratio (p=0.044 and 0.00, respectively) and IGF-1 (p=0.013 and 0.015, respectively). After 12 and 24 months of treatment, group B showed lower height velocity (p<0.001 and 0.049) and QUICKI (both p<0.001) and higher fasting glucose (p=0.001 and 0.015), insulin (p=0.001 and 0.008), Homa-IR (p<0.001 and 0.001) than group A, and HbA1c levels higher at 12 months (p=0.017), although always within the normal range. Conclusions Children considered as affected by GHD on the basis of previous, but not current, AIFA criteria showed a worse auxological and metabolic response, probably confirming that the previous cut-off of 10 ng/dl seems to be too high and those patients may not fully benefit from the GH treatment.