Between-Assay Differences in Serum Growth Hormone (GH) Measurements: Importance in the Diagnosis of GH Deficiency in Childhood

The diagnosis of childhood growth hormone (GH) deficiency is controversial. The usefulness of provocative tests of GH secretion has been questioned for several reasons, one of which involves the large discrepancies in GH measurements among methods and laboratories. Some reports have proposed 10 μg/L as the acceptable GH cutoff value (1), but other values have also been used. GH immunoassays show poor interassay agreement. These assay discrepancies may occur for several reasons: ( a ) the use of different GH calibrators (2); ( b ) the heterogeneity of the GH molecule in human serum (3); ( c ) the interference of endogenous GH binding protein (4); ( d ) the various GH epitope specificities of anti-GH antibodies; and ( e ) the addition of serum to GH calibrators. Because all of these reasons are closely interrelated, their interactions may also accentuate interlaboratory differences in results. The use of methods able to quantify the 22-kDa form of GH exclusively has been proposed as a means of approaching uniformity in results (5). The 22-kDa form is the major circulating fraction and carries the dominant bioactivity. We analyzed serum GH cutoff values, using different immunoassays. We defined the commercial assay SER 66/217 as the Reference Method, and 10 μg/L as the reference cutoff value for this test, based on several years of clinical experience. In the present study, we analyzed 80 samples to compare the Reference Method with nine other commercially available assays. In addition, results of all assays were compared with those of the Delfia Wallac assay (DELFIA 80/505), which utilizes a monoclonal antibody specific for 22-kDa GH. Blood samples (n = 80) were from 42 different individuals (26 …