The Serum Growth Hormone (GH) Response to Provocative Tests Is Dependent on Type of Assay in Autosomal Dominant Isolated GH Deficiency because of an ARG183HIS (R183H) GH-I Gene Mutation

The clinical appearance and genetic basis of familial isolated growth hormone deficiency (IGHD) are heterogeneous and are associated with at least four types of Mendelian disorders: two forms with autosomal recessive inheritance (IGHD type 1A and 1B), one with autosomal dominant inheritance (IGHD type 2), and one with X-linked inheritance (IGHD type 3) (1)(2).Recently, Deladoey et al. (3) reported a new form of IGHD type 2 in four unrelated families. These patients carried an ARG183HIS (R183H) GH-1 mutation. On the basis of in vivo and in vitro experiments, the authors reported that the R183H mutant GH peptide severely impaired GH-regulated secretion. Furthermore, this GH mutant was found to have an effect on GH receptor/GH-binding protein (GHR/GHBP) transcription identical to that of the 22-kDa GH when tested in a human hepatoma cell line (4).Human GH represents a family of proteins rather than a single hormone. Indeed, GH is among the more heterogeneous polypeptide hormones, and the proportions of immunoreactive forms in plasma vary with time after a GH secretory pulse (5). The simultaneous use of an immunoassay that detects most serum GH isoforms (total GH) and one specific for the 22-kDa GH form makes it possible to uncover changes in the pattern of secretion of GH isoforms. Moreover, discrepancies between GH immunologic and biological activities have been reported (6). It has therefore been proposed that the ratio of non-22-kDa GH to 22-kDa GH isoforms may have important implications for normal and abnormal growth (7).We studied two nonrelated patients from Argentina with severe short stature and IGHD type 2 attributable to the R183H GH-1 gene mutation and found that the evaluation of GH response to provocative tests might be misleading in these patients, depending on the type of assay used to assess …