Investigation of factors potentially influencing calcitonin levels in the screening and follow-up for medullary thyroid carcinoma: a cautionary note

Abstract

BackgroundThe malignant transformation of thyroid C cells is associated with an increase in human calcitonin (hCT), which can thus be helpful in the early diagnosis of medullary thyroid carcinoma (MTC). For this reason, hCT levels should be determined in all patients with nodular goitre. Hashimoto’s thyroiditis, nodular goitre and proton pump inhibitor (PPI) therapy are factors reported to influence basal serum hCT concentrations. The diagnostic role of mildly to moderately increased hCT levels is thus a matter of debate. In this study, we attempt to clarify the role of the aforementioned factors.MethodsFrom 2008 to 2009, we collected data from 493 patients who were divided into five groups. We assessed whether there were significant differences in hCT levels between patients with Hashimoto’s thyroiditis, patients with nodular goitre, patients with PPI therapy, and healthy control subjects. In addition, we investigated whether a delayed analysis of blood samples has an effect on serum hCT concentrations.ResultsImmunoradiometric assays (Calcitonin IRMA magnum, MEDIPAN) revealed that the time of analysis did not play a role when low levels were measured. Delayed analysis, however, carried the risk of false low results when serum hCT concentrations were elevated. Men had significantly higher serum hCT levels than women. The serum hCT concentrations of patients with Hashimoto’s thyroiditis and nodular goitre were not significantly different from those of control subjects. Likewise, PPI therapy did not lead to a significant increase in serum hCT concentrations regardless of the presence or absence of nodular goitre.ConclusionsIncreases in serum hCT levels are not necessarily attributable to Hashimoto’s thyroiditis, nodular goitre or the regular use of PPIs and always require further diagnostic attention.

A cut‐off value of basal serum calcitonin for detecting macroscopic medullary thyroid carcinoma

“…Indeed, hypercalcitoninemia can be observed in conditions other than MTC . The sensitivity and the specificity of basal serum CT assays can be improved via stimulated CT testing . Stimulated CT testing was historically done by measuring serum CT levels after intravenous administration of calcium and/or the secretagogue pentagastrin .…”

“…However, pentagastrin is contraindicated during pregnancy and in patients with asthma, coronary artery disease and severe hypertension or duodenal ulcer . Moreover, pentagastrin has become unavailable in many countries . Currently, newer CT assays have significantly improved functional sensitivities.…”

“…8,[10][11][12][13][14][15] The sensitivity and the specificity of basal serum CT assays can be improved via stimulated CT testing. 7,8,12,16,17 Stimulated CT testing was historically done by measuring serum CT levels after intravenous administration of calcium and/or the secretagogue pentagastrin. 1 However, pentagastrin is contraindicated during pregnancy and in patients with asthma, coronary artery disease and severe hypertension or duodenal ulcer.…”

“…18 Moreover, pentagastrin has become unavailable in many countries. 12,16,17 Currently, newer CT assays have significantly improved functional sensitivities. Therefore, most experts believe that there is rarely a need for stimulated CT testing in diagnosis or follow-up of MTC.…”

Calcitonin-Screening und Stimulationstests

“…B. beim Immulite 2000 erst ab > 25 000 pg/ml und beim SELco Calcitonin IRMA erst ab > 200 000 pg/ml). Da die C-Zell-Dichte in der gesunden Schilddrüse von Männern mehr als doppelt so hoch ist als bei Frauen [17] mit entsprechendem Potenzial, hCt basal und stimuliert zu sezernieren, sind konsequenterweise geschlechtsspezifische Referenzbereiche zu fordern [11,16,21]. Die obere Normgrenze liegt bei Männern ca.…”