Endocrine Abstracts

Background: Medullary thyroid carcinoma (MTC) is a rare disease accounting for 1-3% of all thyroid carcinomas. Unfortunately, most patients present with metastasized disease: 70% with cervical lymph node metastasis and 5-10% with distant metastasis. Survival strongly correlates with stage of disease at diagnosis, illustrating the need for early diagnosis. Calcitonin is a well-established tumour marker for MTC, but its use in the screening phase is limited by a high rate of false positives. Among thyroid cancer types, progastrin-releasing peptide (proGRP), is specifically expressed in MTC. Therefore, proGRP is a potential tumour marker for MTC. We studied the value of proGRP as a screening marker for MTC, especially in the range where calcitonin is inconclusive.

Methods: To investigate the potential of proGRP as an additional tumour marker in the diagnostic work up for MTC we took a stepwise approach. First, we prospectively collected serum samples of patients with benign thyroid nodules (benign cohort) and measured serum proGRP concentration. Second, we aimed to establish a reference range and cut-off for proGRP in a clinical setting. Hereto, we measured serum proGRP in a cohort of people where blood was drawn for a vitamin B12 measurement (reference cohort). Third, we investigated the correlation between calcitonin and proGRP in a cohort of patients in whom calcitonin was measured. Serum proGRP and calcitonin concentrations were measured using Lumipulse G1200 (Fujirebio) and Immulite 2000XPi (Siemens) respectively.

Results: The mean serum proGRP concentration in the benign cohort (n = 48) was 36.9 pg/ml (95% CI 33.2-40.5, range 17.8 – 62.3 pg/ml). In the reference cohort (n = 670) mean serum proGRP was 43.9 pg/ml (95% CI 41.2-46.6). The 2.5%-97.5% reference interval was 13.5 – 124.9 pg/ml, with a 90% CI of the upper limit of 103.5 – 154.5. There was a strong correlation between calcitonin and proGRP (r=0.814, P < 0.001, n = 212), especially in the calcitonin concentration range above 100 pg/ml (r=0.810, P < 0.001, n = 54). In the calcitonin concentration range of 10-100 pg/ml no correlation (r= -0.161, P = 0.475, n = 22) was found.

Conclusion: Mean proGRP concentration in the benign cohort was within reference ranges of the reference cohort, suggesting a potential role for proGRP as an additional screening marker for MTC. This was confirmed by the good correlation between proGRP and calcitonin in patients with a calcitonin above 100 pg/ml. Further research should determine whether proGRP can be employed as a screening tool to diagnose MTC.