Search for macrocalcitonin in patients bearing Medullary Thyroid Carcinoma without evidence of clinical and image recurrence

Abstract

Medullary Thyroid Carcinoma (MTC) is a tumor originating from parafollicular cells of the thyroid gland, called C cells, which secrete calcitonin. The MTC is responsible for about 5% of cases of thyroid cancer. Most cases are sporadic, but approximately 30% are associated with a hereditary syndrome known as multiple endocrine neoplasia type 2 (MEN2). MEN2 is an autosomal dominant syndrome in which the predominant manifestation is the MTC. Dominant-activating mutations of the RET tyrosine kinase receptor gene (RET) play a fundamental role in the development of MTC whose more important tumor marker, after total thyroidectomy, is the serum calcitonin. Its determination is crucial for the evaluation and long-term management of patients with MTC helping clinicians in detecting cure or local/distant relapse after initial thyroidectomy. However, in the follow-up, some patients maintain calcitonin persistently increased without evidence of relapse or metastasis. This may lead to a pitfall regarding the value of calcitonin and the apparent absence of a metastatic site suggests possible interferences in the immunometric calcitonin assay. In fact, this artifact has been observed in some cases of macroprolactinomas and macro-TSH in that the increased immunologic levels of those peptides do not reflect a true disease. Accordingly, we propose to search for "macrocalcitonin" in sera from this specific group of patients, once the finding of a negative result could reflect better the pool of calcitonin-producing cells during tumor progression. Moreover, this search will allow a more reliable and specific measure of calcitonin in determining the state of the disease.(AU)