Measurement of plasma free and total growth hormone concentrations in patients with growth hormone antibodies developed in response to therapy.

Abstract

Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0, 30.7 and 13.2 micrograms/1, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies.