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Heterophilic antibodies may be a cause of falsely low total IGF1 levels

Department of Internal Medicine, Erasmus MC, Room D425, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands¹ Department of Internal Medicine, St Antonius Ziekenhuis, Nieuwegein, The Netherlands² Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands³ Department of Clinical Chemistry, St Antonius Ziekenhuis, Nieuwegein, The Netherlands

(Correspondence should be addressed to J A M J L Janssen; Email: j.a.m.j.l.janssen{at}erasmusmc.nl)

Background: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions.

Case: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal.

Conclusion: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.