Gonadotropin therapy failure secondary to human chorionic gonadotropin-induced antibodies

A 15-yr-old male with the diagnosis of Kallmann's syndrome manifested secondary gonadal resistance during a third treatment course of hCG. A serum sample obtained 6 months after failure of the patient to respond to hCG bound [125I]hCG 60% at a 1:2 dilution of serum; 50% at 1.5; 28% at 1:50; 21% at 1:100; and less than 5% at a 1:500 dilution. Serial sampling of the patient's serum over a 22-month period demonstrated a progressive decline in binding capacity, decreasing to 32% binding of [125I]hCG at a 1:2 dilution of serum. The data demonstrated that the patient produced a low affinity, high capacity binding substance with a Ka of 5 x 10(7) liters/M and a R0 of 1.8 x 10(16) sites/g gamma-globulin. The binding substance appeared to be a gamma-globulin of the immunoglobulin G class, which bound labeled hCG and human LH (hLH) more avidly than it bound hFSH and interfered with the biological response to hCG therapy. These data further indicated that antibodies produced against hCG may bind other endogenous glycoproteins such as hLH, hFSH, and hTSH. Although binding to hTSH did not occur in this patient, the presence of a common beta-chain in the molecular structures of hLH, hFSH, hCG, and TSH makes such a potential occurrence not implausible. Despite the apparent infrequency of the development of clinically observable interference with the biological activity of hLH/hCG in hCG-treated patients, this report indicates that a potential hazard exists. The possibility should be considered in the decision to treat a patient with normal gonadotropin secretion with exogenous gonadotropins.