Differences in Serum GH Cut-Off Values for Pharmacological Tests of GH Secretion Depend on the Serum GH Method

Abstract

Background: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5–10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. Methods: Fifty pre-pubertal patients with short stature (height ≤–2 SDS and GV ≤–1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). Results: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. Conclusion: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.

Is BaF3 Bioassay Useful to Identify Patients with Bioinactive Growth Hormone?

“…It must be considered in the analysis that, when Kowarski described the syndrome of bioinactive GH, serum GH levels were measured by radioimmunoassay using polyclonal antibodies that recognized all forms of serum GH; later on, monoclonal antibodies which measure the 22 Kd form were used. Moreover, the advent of methodologies based on the interaction with the GH receptor binding sites 13,14 reduced the chances of discrepancy between immunoreactivity and bioactivity. However, the finding of discrepancies between immuno-and bio-assays of serum GH still suggests the presence of mutations in the GH-1 gene that cause the production of GH oligomers with low biological activity 15 or abnormal post-translational processing of GH 16,17 .…”

How to Optimally Manage Growth Hormone Therapy: Survey of Chilean Pediatric Endocrinologists

“…One interesting study showed that the cut-off value is based on the serum GH method. They concluded that a value of 10.8 ng/ml is the cut-off for a GH deficit diagnosis if the GH test is done by immunofluorometric assay [22]. We suggest caution with the interpretation of the GH test results and using them in association with the IGF-1 and IGFBP3 serum levels (using SDS corrected for age, sex and BMI).…”

Predictor Variables of Developing Anterior Pituitary Deficiencies in a Group of Paediatric Patients with Central Diabetes Insipidus and Langerhans Cell Histiocytosis

“…GHD was defined as follows: maximum serum GH response less than 6.1 ng/mL (IRP IS80/505) or 4.7 ng/ml (IRP IS 98/5742) to 2 pharmacological tests [19,20] .…”