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"Hook Effect" in Calcitonin Immunoradiometric Assay in Patients with Metastatic Medullary Thyroid Carcinoma: Case Report and Review of the Literature

Department of Medicine, Division of Endocrinology (R.L., M.-F.L.), and Department of Biochemistry (M.M.), Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada; and Collaborative Research for Effective Diagnostics (C.E.A.) and Division of Clinical Biochemistry (G.D.F.), Faculté de Médecine et des Sciences de la Santé (R.L., M.-F.L., C.E.A., G.D.F.), Université de Sherbrooke, Sherbrooke, Québec, Canada

Address all correspondence and requests for reprints to: Dr. Guy Fink, Division of Clinical Biochemistry, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Québec, Canada J1H 5N4. E-mail: gfink.chus{at}ssss.gouv.qc.ca.

Context: Calcitonin is a well-established tumor marker for medullary thyroid carcinoma (MTC). Because surgery is the only effective treatment for patients with MTC, the postoperative level of serum calcitonin will dictate whether residual disease was left behind and whether reintervention is necessary.

Results: We describe here the case of a 41-yr-old man with metastatic MTC. Despite extensive disease in the neck as well as metastatic lesions in the liver, his serum calcitonin, measured with a commercial one-step immunoradiometric assay, was only minimally elevated (244 ng/liter). After serial dilutions, a nonlinear relationship became evident, suggesting the presence of a "hook effect." Treatment of the serum with heterophilic blocking reagent revealed no change. Calcitonin was then measured with a different immunoradiometric assay and revealed a much higher level. Similar discrepancies were found in different samples from various patients when analyzed with different calcitonin immunoassays.

Conclusion: To our knowledge, this is the first reported case of a phenomenon such as the hook effect in a calcitonin immunoradiometric assay in patients with MTC. Being aware of this phenomenon is important, because a low calcitonin result could give false reassurance to both the patient and the clinician and could dramatically change the prognosis of the patient.

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				M. Tommasi and S. Raspanti Comparison of Calcitonin Determinations by Polyclonal and Monoclonal IRMAs Clin. Chem., April 1, 2007; 53(4): 798 - 799. [Full Text] [PDF]

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