Bioactive GH-like immunoglobulins G in active acromegaly: response to long-term treatment with bromocriptine

In acromegaly, certain forms of circulating immunoreactive hGH are not true GH but IgGs which possess GH biological activity (bioactive GH-like IgGs). In this study, we tested the effect of bromocriptine on circulating bioactive GH-like IgGs in an acromegalic woman. Increasing doses of oral bromocriptine (2.5, 5.0 and 7.5 mg/day) were administered (for 2, 8 and 6 months respectively). TRH tests were performed before treatment and at the end of treatment with each dose. The patient was without detectable pituitary or extra-pituitary tumour by magnetic resonance imaging. Her serum contained bioactive GH-like IgGs equivalent to 240 mU/l of hGH and elevated insulin-like growth factor I (IGF-I; 9500 U/l). Basal hGH was 12.8 mU/l and increased to 220 mU/l 15 min after TRH (200 micrograms, i.v.). In addition, in the basal samples of each test we measured total IgGs (radial immunodiffusion), bioactive GH-like IgGs (isolated by Sephadex and protein A affinity chromatography and assayed using the Nb2 cell assay) and IGF-I(RIA). Bromocriptine treatment gradually reduced serum levels of bioactive GH-like IgGs and IGF-I, with significant falls observed first at 10 months of treatment. Bioactive GH-like IgGs were 240, 240, 36.0 and < 0.124 mU/l and IGF-I levels were 9500, 8700, 4000 and 3100 U/l at 0, 2, 10 and 16 months of treatment, respectively. In contrast, IR-hGH response to TRH decreased after 2 months of treatment to 89 mU/l and to 49.2 mU/l at the end of the study while basal IR-hGH remained between 13 and 8.4 mU/l. Basal PRL fell to almost undetectable levels. Bromocriptine treatment decreased the GH response to TRH and the serum concentration of bioactive GH-like IgGs and IGF-I. The striking similarity between the pattern of decrease of serum bioactive GH-like IgGs and IGF-I supports the presence of an immuno component in our patient's acromegaly.