Laboratory assessment of GH.

The diagnosis of growth hormone (GH) deficiency is based primarily on clinical criteria. In paediatric endocrinology, auxological evaluation leads to the diagnosis, while in adult endocrinology evidence of severe pituitary disease is associated with GH deficiency. Final proof of the diagnosis, however, is sought by measurement of GH levels in serum after dynamic provocative testing of GH secretion. Although arbitrary cut-off levels exist, below which the maximum GH peak should be found in different provocative tests, these recommendations have to be considered vague in the light of the considerable heterogeneity between results from different commercially available GH assays. Factors influencing the results of GH measurement by immunoassay are the heterogeneity of molecular isoforms of circulating GH, assay design, standard matrix, choice of reference preparation for calibration and, to a considerable extent, the epitope specificity of the antibodies used. Ideally, GH should be measured by a true somatogenic bioassay. Such assays are too cumbersome for routine use, however, and in most instances are only suitable for investigation of purified GH preparations rather than quantification of GH levels in serum samples. Significant progress was made recently with the concept of immunofunctional measurement of GH levels, in which only GH molecules having both receptor interaction sites necessary for initiation of the signal transduction process in target cells are translated into an assay signal. Immunofunctionally measured GH levels are, therefore, closer to the results from bioassays than the determination of arbitrary immunoreactivity of GH isoforms with a given antibody or set of antibodies in conventional immunoassays. In the context of establishing a diagnosis of GH deficiency, it is mandatory that techniques for GH measurement are standardized more rigidly before recommendations on meaningful cut-off levels for different provocative tests are made.