Pseudohypergonadotropinemia and pseudohyperprolactinemia induced by heterophilic antibodies?

The serum of 20 apparently hypergonadotropic and/or hyperprolactinemic patients (14 females, 6 males, ages 13-75 years) without evidence of neoplasia or pituitary adenomas was found to contain a large amount of molecular material (MW ca. 100,000) resulting in factitiously elevated levels of peptide hormones when measured by double-antibody radioimmunoassay with a long second incubation time. The interference by this material with the test system could be avoided by using polyethylene glycol (PEG) for the separation of free from bound antigen, or by preincubation of the samples with normal rabbit serum. No definite disease process can as yet be linked to these findings. They rather seem to be caused by the presence of heterophilic antibodies in serum, as the serum of approximately one half of the patients was found to give a positive Paul-Bunnell test. Moreover, the beta hCG activity in the urine of these patients was low, probably as a result of the low clearance of substances with igh MW. It is therefore suggested to apply to following diagnostic measures before clinical consequences are being considered in a case of hypergonadotropinemia and/or hyperprolactinemia without pertinent clinical findings: (1) validation of the immunoassay, (2) preincubation of the samples with serum from other species, (3) the use of another separation procedure than the double-antibody method, and (4) measurement of the respective hormone in urine.