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This version published online on November 8, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1429
A more recent version of this article appeared on February 1, 2006
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Submitted on June 28, 2005
Accepted on October 27, 2005

"Hook-effect in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature"

Rébecca Leboeuf, Marie-France Langlois, Marc Martin, Charaf E. Ahnadi, and Guy D. Fink*

Department of Medicine, Division of Endocrinology, Department of Biochemistry, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Collaborative Research for Effective Diagnostics, and Division of Clinical Biochemistry, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada

* To whom correspondence should be addressed. E-mail: gfink.chus{at}ssss.gouv.qc.ca.

Context: Calcitonin is a well established tumor marker for medullary thyroid carcinoma (MTC). Since surgery is the only effective treatment for patients with MTC, the post operative level of serum calcitonin will dictate if residual disease was left behind and if a re-intervention is necessary.

Results: We describe here the case of 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/L). After serial dilutions, a non-linear 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 like the "hook effect" in a calcitonin IRMA assay in patients with MTC. Being aware of this phenomenon is important as a low calcitonin result could give false reassurance to both the patient and the clinician, and can dramatically change the prognosis of the patient.


Key words: medullary thyroid carcinoma • calcitonin • hook-effect




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