Clinical and biochemical predictors of Permanent Growth Hormone Deficiency (pGHD) at retesting

Background and Aims: Retesting subjects treated with GH throughout childhood at attainment of final height is of importance to identify those having pGHD and needing replacement treatment during transition years and adulthood, and to avoid overtreatment of GH sufficient subjects. This study aimed at evaluating the clinical and biochemical features of patients diagnosed of isolated idiopathic (II) GHD in childhood at retesting to verify the prevalence of permanent and transient GHD (tGHD), and the clinical outcomes. We also explored the possible predictors of pGHD. Methods: We retrospectively evaluated 55 subjects (30 females; mean age 15.3+/-1.56yr) who were retested using the GHRH+ arginine stimulation test (ATT). Subjects having pGHD and tGHD were compared. At diagnosis all patients underwent an ATT as first test followed by glucagon (59%), L-Dopa (20%), clonidine (6%) or GHRH+ATT (16%) tolerance tests. Auxological and biochemical parameters, bone age at diagnosis, at 6 and 12 months from the start of replacement therapy and at retesting were recorded. Possible associations with the features of the pituitary gland at MRI at diagnosis, and best GH peak at diagnosis, and at retesting were evaluated. Results: The prevalence of pGHD was 16.3%. Both catch-up growth in the first year of therapy and total height gain at final stature were greater in the pGHD group that had also a greater BMI at diagnosis, at 6 and 12 months on GH therapy compared with the tGHD group. They had also a more pronounced and persistent bone age delay during GH therapy. Subjects with pGHD had a smaller pituitary volume at MRI than the tGHD group, and morphological changes in the pituitary gland were more frequently found. The levels of the GH peaks at diagnosis correlated with the GH peak at retesting. IGF1 and IGFBP3 at diagnosis were lower in the pGHD. At discontinuation of therapy, the biochemical marker that best differentiated the subgroups was IGFBP3 (PGHD 3285.80±505.18ng/ml vs tGHD 4297.67±477.68ng/ml, P<0.05) as a potential marker of persistent GHD in the age of transition. Conclusions: Permanent GHD is not frequent among patients diagnosed of IIGHD in childhood. However, they do seem to have some distinctive features that if confirmed in a larger series could help identify which subjects need retesting and possibly further GH treatment. Furthermore, the correlation between peak GH at testing at diagnosis, and at retesting using the GHRH+ ATT confirms the diagnostic and predictive potential of this combined test.