J. Endocrinol. Invest. 24: 361-369, 2001 CASE REPORT A case of spurious hypercalcitoninemia: A cautionary tale on the use of plasma calcitonin assays in the screening of patients with thyroid nodules for neoplasia 1 G.I. Uwaifo*, A.T. Remaley**, M. Stene***, J.e. Reynolds****, P.M. Yen*****, R.H. Snider******, K.L. Becker******, and N.J. Sarlis***** *Developmental Endocrinology Branch, National Institutes of Child Health and Human Development, **Clinical Pathology Department and ****Nuclear Medicine Department, Clinical Center, National Institutes of Health; *****Clinical Endocrinology Branch, National Institutes of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD; ***Peptide Laboratory, Esoterix Endocrinology, Calabasas Hills, CA; ******Metabolic Research Department, VA Medical Center, Washington, DC, USA ABSTRACT. The measurement of plasma CT has an important role as a screening test for me- dullary thyroid carcinoma (MTC) in patients with thyroid nodules. However, elevated plasma CT levels should be interpreted within the context of the overall clinical picture in each individual case and carefully validated before therapeutic deci- sions are made. We present the case of a 17-yr- old girl who was referred to us with a thyroid nodule and elevated plasma CT levels, as mea- sured by a one-site RIA not involving prior plas- ma extraction. Plasma CT was re-measured us- ing two different methods, a RIA with prior plasma extraction and a two-site immunoche- miluminometric assay (lCMA), and was either very low or undetectable. Subsequently, samples were re-assayed using the initially applied CT INTRODUCTION While nodular thyroid disease is common, the inci- dence and prevalence of medullary thyroid cancer (MTC) is low (1-3), as it accounts for less than 10% of thyroid cancers (3, 4). As currently no effective curative treatment options exist for MTC other than 1This paper was presented in part at the 82 nd Annual Meeting of the Endocrine Society, Toronto, ON, Canada, 2000. Key-words: Calcitonin, Hashimoto's thyroiditis, immunoassay, medullary thyroid carcinoma, C-cell hyperplaSia. Correspondence: Dr. Nicholas J. Sari is, Investigator, CEB, NIDDK, National Institutes of Health (NIH), Bldg. 10, Rm. 8D12C, 10 Center Drive - MSC 1758, Bethesda, MD 20892-1758, USA. E-mail: njsarlis@helix.nih.gov Accepted January 3, 2001 . 361 RIA; plasma CT levels were again found to be el- evated. These elevations were of a spurious na- ture, probably caused by the presence of an unidentified substance in the patient's plasma in- terfering with the measurement of CT in the ini- tially used RIA. Our patient was eventually diag- nosed with Hashimoto's thyroiditis, and had no evidence of MTC. As several conditions can cause either true or spurious hypercalcitoninemia, we suggest that elevated plasma CT levels should be confirmed at least once before other exten- sive diagnostic investigations are initiated or thyroidectomy is recommended. Finally, the as- say selected should detect only the mature CT molecule. (J. Endocrinol. Invest. 24: 361-369,2001) @2001, Editrice Kurtis surgery performed early in the natural history of the disease, i.e. in the absence of extraglandular tumor spread (5, 6), there is great need for timely diag- nosis of this neoplasm. Although the majority of MTC cases are sporadic, about 25% of cases are of familial nature, and caused by an inherited mutation in the RET onco- gene (7, 8). CT assays have proven very useful for screening for MTC in cases of familial occurrence of this tumor (8, 9). When basal plasma CT levels are higher than 200 pg/ml, in cases with high pre-test probability of MTC [i.e. in a member of a multiple endocrine neoplasia type 2 (MEN2) kindred with a thyroid nodule], the test has a sensitivity of 70% and a specificity of 98% (10-12). Moreover, CT assays have greater utility in the diagnosis of MTC in com-