The diagnosis of childhood growth hormone insufficiency and growth hormone resistance

Growth hormone insufficiency (GHI) is an uncommon though treatable cause of retarded growth velocity and short stature in childhood, the diagnosis generally requiring the demonstration of a subnormal growth hormone (GH) response to a physiological or pharmacological stimulus. Physiological and pharmacological GH release is a continuous variable and the relationship between spontaneous GH secretion and height velocity is asymptotic. Cut-off points for defining GH insufficiency are largely derived from adult observations, but have been extrapolated to children, for whom normative data are relatively scanty. There is no absolute cut-off that discriminates between normal and abnormal GH response. Moreover, poor reproducibility, sensitivity and specificity of the many dynamic tests available, particularly when performed in the very young child or in early adolescence, together with the confounding effects of assay performance, further weaken the diagnostic efficiency of biochemical investigations. Between 20-40% of children retested at the completion of GH therapy demonstrate a normal GH response to a provocative stimulus. Such limitations mitigate against over-reliance on GH provocation tests in diagnosis, and further emphasize the importance of careful auxology in evaluating the short child.