CONTEX: Although GH values measured by an immunoassay usually reflect GH bioactivities, discrepancy exists between immunoactivity and bioactivity in a rare condition known as 'bioinactive GH'.
Objective: To report an immunologically anomalous but considerably bioactive GH.
Methods: We performed mutational and functional analyses of GH1 in a 7-year-old Japanese boy with short stature (-3.0 s.d.) in whom serum GH values measured with a Tosoh immunoassay kit were all undetectable in three provocation tests, whereas urine GH value measured with a Hitachi immunoassay kit was within the normal range. Serum IGF-1 was at a low-normal range, and IGF-binding protein-3 was below the normal range.
Results: Mutation analysis showed a missense GH produced by a novel GH1 mutation (p.D116E) of paternal origin and a frameshift mutation (p.Q68fsX106) of maternal origin. Genotype-phenotype correlations in this family and in vitro functional studies indicated that the p.D116E-GH was immeasurable with the Tosoh kit but was measurable, though maybe not precise, with a Daiichi kit, and had a reduced in vivo bioactivity. The p.Q68fsX106 yielded no GH protein.
Conclusions: The results suggest that the p.D116E affects the GH epitope primarily recognized by the Tosoh kit but not by the Hitachi or the Daiichi kits, thereby producing an immunologically anomalous but considerably bioactive GH. The presence of such a hormone discordant for immunoactivity and bioactivity should be kept in mind, to allow for an appropriate assessment of endocrine data.