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Potency and Tolerance of Calcitonin Stimulation with High Dose ...

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Introduction<br />

Human calcitonin (hCT) is a tumor marker essential to the diagnosis <strong>and</strong> follow-up <strong>of</strong><br />

medullary thyroid cancer (MTC ) (1-4). Current European consensus recommends hCT<br />

measurement when initially evaluating thyroid nodules (5). If hCT is mildly elevated,<br />

European centers commonly perform a confirmatory test <strong>with</strong> intravenous pentagastrin<br />

stimulation (3, 6-8). A less popular alternative stimulation test uses a short intravenous<br />

calcium infusion (3, 6). <strong>Stimulation</strong> testing also may aid early risk stratification in patients<br />

<strong>with</strong> MTC (4).<br />

For reasons including the unavailability <strong>of</strong> pentagastrin in the US, the American<br />

Thyroid Association has not recommended routine hCT measurement (9). However, a recent<br />

U.S. cost-effectiveness study (10), though not <strong>with</strong>out flaws, provides data favoring such<br />

testing .<br />

Key to employing stimulated hCT measurement clinically are the reliability <strong>and</strong><br />

relevance to everyday practice <strong>of</strong> healthy adult reference values. Most published reference<br />

values for stimulation tests were obtained in small series not rigorously screened for thyroid<br />

abnormality (2, 6, 7, 11). Calcium stimulation was investigated in only a few studies (12)<br />

using disparate regimens, e.g., 10% calcium gluconate dosages <strong>of</strong> 2.0-2.5 mg/kg body weight,<br />

injection over 30 sec-5 min (3, 13-15).<br />

Indeed, hCT reference ranges generally were obtained <strong>with</strong> competitive<br />

radioimmunoassays <strong>and</strong> do not apply to automated non-competitive chemiluminescent<br />

immunometric assays.<br />

Differences in hCT measurement are evident even <strong>with</strong>in the radioimmunoassay<br />

class, emphasizing the need to re-evaluate reference ranges <strong>and</strong> cut-<strong>of</strong>f values for each assay<br />

individually (16).<br />

We therefore conducted this study to define the normal ranges on a commonly used<br />

chemiluminescent immunometric assay <strong>of</strong> serum hCT values in healthy adults before <strong>and</strong><br />

after pentagastrin or high-dose calcium stimulation,. We also sought to assess these<br />

secretagogues’ tolerability in such subjects..<br />

3

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