Total Immunoreactive Calcitonin

Introduction
There are two SAS centres for measurement of plasma calcitonin, namely Hammersmith and Newcastle. Each centre uses a different assay. The assay characteristics and reference ranges of the two assays are different. Absolute values of plasma calcitonin should not be compared between different laboratories, and a given value (s) should be interpreted in relation to the reference range of the same lab. However, the clinical application for measurement, and patient preparation are the same for the two centres.

Clinical application
Medullary thyroid carcinoma (MCT) is a tumour of the calcitonin (CT)-producing C-cells of the thyroid gland. It occurs in a sporadic and in an inherited form. The neoplastic C cells of the thyroid gland produce abnormally high amounts of CT. The basal concentrations of the hormone in plasma are diagnostically elevated in many patients with MCT. However, basal levels of CT are indistinguishable from normal in early disease, when there is only C-cell hyperplasia. In these patients, early diagnosis could be made when provocative tests of CT release with calcium and/or pentagastrin are applied. Serial measurement of plasma CT can be used to monitor therapy. Basal plasma CT levels can also be increased in malignancies other than MCT, such as those of the lung, breast, pancreas and a few rare neuroendocrine tumours and some benign conditions including renal failure and pernicious anaemia. However, patients with these conditions do not get an exaggerated response to pentagastrin stimulation.

Patient Preparation
After an overnight fast, take blood (5mL) into a syringe and then transfer into a lithium heparin tube or a green top vacutainer.

Measurement of plasma calcitonin after an overnight fast is usually sufficient for the diagnosis of MTC. However, in some patients with early disease, basal CT concentrations are not always different from those of normal subjects. Provocative tests of CT secretion may be necessary to establish the diagnosis.

These tests should be performed after an overnight fast and the patient should be recumbent throughout the test. It includes:

Pentagastrin test
Take blood (5mL) for basal CT. Inject pentagastrin solution (0.5(g/kg body weight in 2 ml normal saline) intravenously(iv) within 10-15 sec. Take further blood samples (5mL) 2,5,10 and 15 min later.

Short calcium infusion test
Take blood (5mL) for basal CT. Slowly infuse calcium gluconate (2.5 mg calcium/kg body weight, 10% solution in saline, 10-15mL iv within 30-60 sec. Take further blood samples (5mL) 2,5 and 10 min later.

Combined pentagastrin and calcium infusion test
Take blood (5mL) for basal CT. Infuse iv within 30 sec a mixture of pentagastrin (solution (0.5(g/kg body weight in 2 ml normal saline) and calcium gluconate (2.5 mg calcium/kg body weight). Take further blood samples (5mL) 2,5,10 and 15 min later.

Sample Preparation
If using vacutainers place on ice or transfer each sample promptly to a plastic heparin tube cooled in ice. Within 30 min, separate the plasma in a refrigerated centrifuge at 4C. Transfer the plasma to 2 plastic tubes (preferably 12 x 50 mm) and store at –20C. Send one portion (1mL) of each plasma to the SAS laboratory at Hammersmith.

Ensure the samples remain frozen during transport. Retain the remaining portion frozen in reserve.

Reference Range
The assay measures total immunoreactive calcitonin in plasma. This includes intact molecule, Procalcitonin and calcitonin fragments.

Normal basal total ir-CT is <0.08 (g/l (<80pg/ml). After pentagastrin stimulation the peak ir-CT level in normal subjects is <0.30 (g/l.

Centre offering this assay
London Imperial Charing Cross Endocrine Laboratory

References
Wells SA, Jr, Baylin SB, Linehan WM, Farrell RE, Cox EB and Cooper CW.

“Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland”.

Ann Surg 1978; 188 (2): 139-141.

Saad MF, Ordonez NG, Rashid RK, Guido JJ, Hill CS, Hickey RC and Samaan NA.

“ Medullary carcinoma of the thyroid: a study of the clinical features and prognostic factors in 161 patients”.

Medicine 1984; 63 (6): 319-342.

Samaan NA, Castillo S ,Schltz PN, Khalil KG and Johnston DA.

“Serum calcitonin after pentagastrin stimulation in patients with bronchogenic and breast cancer compared to that in patients with medullary thyroid carcinoma”.

J Clin Endocrinol Metab 1980, 51: 237-241.

Girgis SI and MacIntyre I.

“ The calcitonin gene peptide family: molecular biology, physiology, pharmacology and relations to malignancy”.

In: Endocrine Tumors, Mazzaferri EL and Samaan NA (eds), 1993; Blackwell Scientic Publications, pp 671-686.

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