Biochemical diagnostic strategies in the evaluation of short stature: The diagnosis of insulin-like growth factor deficiency

The cornerstones in the evaluation of short stature are auxology and biochemical testing. Traditionally, the diagnosis of growth hormone (GH) deficiency has been based upon measurement of serum concentrations of GH following either physiological or pharmacological stimulation, or determination of spontaneous GH secretory patterns. Assessment of pituitary GH secretion is, however, fraught with problems, including the nonphysiological nature of provocative testing, the reliance on arbitrary definitions of subnormal responses, the inadequate attention paid to age- and puberty-related variability, and the dependence upon assays with marginal concordancy. It is proposed that the evaluation of short stature is best pursued by careful auxology plus assessment of the insulin-like growth factor (IGF) axis, with particular attention to measurements of serum concentrations of IGF-I and IGF-binding protein-3. The diagnosis of IGF deficiency can then be readily established, and its etiology pursued logically.