Growth Response to Recombinant Human Growth Hormone (GH) in Children with Idiopathic Growth Retardation by Level of Maximum GH Peak during GH Stimulation Tests

Abstract

Due to their lack of reproducibility, it is unlikely that GH stimulation tests can provide reliable diagnostic information to distinguish partial isolated GH deficiency (GHD) from idiopathic short stature (ISS). We hypothesized that the classical distinction between these groups, essentially based on stimulatory GH peaks, is artificial and that, as a consequence, the average response to GH treatment will not be different between them. The hypothesized lack of prognostic validity of stimulatory GH peaks was studied in 435 prepubertal children with nonorganic growth retardation. Children were categorized as ‘severe GHD’, ‘partial GHD’ or ‘ISS’, if the maximum rise in their serum GH during two GH stimulation tests was 0– 10 mU/l, 10–20 mU/l, or >20 mU/l, respectively. Children with ‘partial GHD’ had short-term (1- and 2-year) and long-term (till final adult height) growth responses similar to those of children with ISS, significantly lower than the response seen in children with ‘severe GHD’. In children with stimulatory GH peaks >10 mU/l, including those currently considered partially GH deficient, the maximum GH peak was not a significant determinant of growth response in the short or the long term. In conclusion, ‘partial GHD’ is ill defined and cannot be distinguished from ISS based on the currently applied auxological or GH stimulation test criteria alone. More research is required for better identification of (all) children who will respond to GH treatment, whether or not GH deficient.

A brief review of the use and utility of growth hormone stimulation testing in the NCGS: Do we need to do provocative GH testing?

“…Other investigators have also reported that peak GH values obtained during GHST are poor predictors of subsequent growth for all but the lowest peak GH values [13,14]. Interestingly, Wyatt et al [15] noted in 1995 that while 80% of the pediatric endocrinologists who responded to their questionnaire used two GH stimulation tests, only 32% believe the results of such tests predicted a response to therapy.…”

Validation of a Mathematical Model Predicting the Response to Growth Hormone Treatment in Prepubertal Children with Idiopathic Growth Hormone Deficiency

“…The severity of GHD was more pronounced in our subjects which is shown by a significantly lower mean GH peak after the provocation test. In other words, in the original group patients with less severe GHD were included, and it is well known that these patients will respond less favorable to GH treatment [13]. In addition, our group was composed from only 2 university centers applying rather stringent criteria for the diagnosis and laboratory methods which may help to reduce the variability arising from data composition from a large number of centers.…”

Is growth hormone stimulation testing in children still appropriate?

“…Van den Broeck et al [39] reviewed the Dutch Growth Hormone Register and analyzed whether longterm response to therapy of 435 children could be predicted by peak GH response at the time of diagnosis. Children were diagnosed as severe GHD, partial GHD, or ISS based on GH response to GH stimulation tests (<10 mU/L or 5 ng/mL, 10-20 mU/L or 5-10 ng/mL, >20 mU/L or 10 ng/mL, respectively).…”

“…The response to therapy was significantly better in children with severe GHD, but was not statistically different between children with partial GHD and those with ISS. The authors conclude that ''there is a lack of prognostic validity of GH stimulation tests as they are currently applied'' [39].…”