Thalita G. Alves
UNEXPECTED HIGH LEVEL OF CALCITONIN IN PATIENTS WITH APPARENTLY CURED MEDULLARY THYROID CARCINOMA: A NOVEL PITFALL IN THE IMMUNOASSAY – THE “MACROCALCITONIN”
Thalita Goulart Alves (Universidade Federal de São Paulo – Laboratório de Endocrinologia Molecular e Translacional)
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Introduction: Calcitonin (CT) represents a sensitive marker of medullary thyroid carcinoma (MTC). Clinical challenge may rise when patient presents mild CT increase without corresponding structural disease found by imaging scan. This lack of biochemical-clinical correlation may suggest assay interferences, which can delay a suitable approach for the patients. The objective of the study was to investigate the presence of new assay interferences in the serum of MTC patients who are apparently without structural disease.
Methods: CT was measured by an in-house immunofluorometric assay from 25 patients (17F:8M, aged 16-67 years) with MTC. After precipitation with polyethylene glycol (PEG) samples were subjected to gel-filtration on high performance liquid chromatography-HPLC (Biosep S-3000 column, 30x6.7mm, Phenomenex) and to affinity chromatography on Protein A Sepharose (GE Healthcare). Results showed that serum CT ranged from 21-19.800 pg/mL. Three patients showed low recovery of CT (1-7%) after PEG when compared with recovery of the others (55-135%). Elution profile on HPLC showed that almost all of the immunometric CT from these three patients behaved as a high-molecular-weight aggregate (MW>300 kDa). Additionally, when these samples were applied to the protein A sepharose, CT immunoreactivity was almost completely retained on the column and only released after lowering pH to 2.8.
Conclusion: Our results show for the first time the presence of a novel pitfall in the CT immunoassay – the “Macrocalcitonin”. Its etiology, frequency and meaning remain to be defined. However, rather than a simple artifact, its recognition has a noteworthy interest since it can help clinicians on the MTC follow-up, avoiding unnecessary investigation and overtreatment.