Endocrine Abstracts

Background: Patients with medullary thyroid carcinoma (MTC), a neuroendocrine tumour derived from the parafollicular C-cells, often present with metastasized disease. Survival strongly correlates with stage of disease at diagnosis, illustrating the need for early diagnosis. Calcitonin (CT), a well-established tumour marker for MTC, is limited by a high rate of false positives in the screening phase. Promising new markers for MTC are procalcitonin (PCT) and progastrin releasing peptide (proGRP). Where literature has proven non-inferiority for PCT, evidence is lacking for proGRP. Previous studies looking into proGRP had small sample size, mostly retrospective design and large variability in reported sensitivity, specificity and cut-off value. Therefore, the present study prospectively evaluated the clinical performance of proGRP in a large series of patients with pathology proven diagnosis of MTC vs other thyroid disease.

Methods: Serum samples from 278 patients that underwent total thyroidectomy for either benign thyroid disease (n =117), differentiated and other thyroid carcinomas (non-MTC) (n =137) or MTC (n =24) were collected before surgery. Serum proGRP and PCT concentrations were measured using Lumipulse G1200 (Fujirebio), CT was measured using Immulite 2000XPi (Siemens). Cut-offs for CT (10 pg/mL) and PCT (0.15 ng/mL) were based on literature. Cut-off for proGRP (100 pg/mL) was based on previous studies and validated in a local cohort.

Results: Median proGRP concentration (300.5; 69.7 – 1249.8) was significantly higher in MTC compared with benign thyroid disease (30.3; 23.9 – 38.2) and non-MTC (27.1; 21.9 – 34.5) (P < 0.001). Despite, having a good specificity of 99.6%, sensitivity of proGRP was low (70.4%). Therefore, proGRP did not perform better than CT in discriminating between MTC and benign thyroid disease or non-MTC in a screening setting. As expected, PCT performed as good as CT with a sensitivity off 100% and a specificity of 98.5% (CT sensitivity and specificity were 100% and 98.8% respectively). Combining proGRP and CT lead to a perfect specificity (100%), but decreased sensitivity even further (69.2%).

Conclusion: ProGRP alone does not perform better as a screening marker for MTC than CT. Furthermore, there is no added value of combining proGRP and CT in a two-step approach in cases where calcitonin concentration is inconclusive. This study supports the evidence in literature for PCT as a tumour marker in MTC, with PCT having clear advantages over CT given the better (pre-) analytical characteristics, such as inter-assay comparability and protein stability.