Impact of Routine Measurement of Serum Calcitonin on the Diagnosis and Outcome of Medullary Thyroid Cancer: Experience in 10,864 Patients with Nodular Thyroid Disorders

Abstract

The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce

“…Routine measurement of serum thyroglobulin for initial evaluation of thyroid nodules is not recommended-Recommendation F Serum calcitonin measurement. The utility of serum calcitonin has been evaluated in a series of prospective, nonrandomized studies (24)(25)(26). The data suggest that the use of routine serum calcitonin for screening may detect C-cell hyperplasia and medullary thyroid cancer at an earlier stage FIG.…”

Molecular markers in the diagnosis of thyroid nodules

“…More significant is that non-specific cytological features may wrongly suggest tumors other than MTC. These false negative diagnoses result in the failure to cytologically diagnose MTC, and lower cytological sensitivity for MTC (45,(47)(48)(49)(50)(51)(52)(53)(54)). An abstract reporting 14 samples (from 13 patients) that positively expressed the MTC gene expression signature in the Afirma GEC rare neoplasm cassettes found that all 14 were confirmed as MTC on histopathology (55).…”

Nodular disease and parafollicular C-cell distribution: results from a prospective and retrospective clinico-pathological study on the thyroid isthmus

“…MTC arises from the neural crestderived parafollicular C cells (4), presents in the familial form with a genetic mutation in 25% of the cases (1,5), and is the most aggressive of differentiated thyroid carcinomas, with a survival rate at 10 years approaching 40-50% and depending on the tumor stage at diagnosis (3,27). In the literature, a convincing body of evidence exists showing that when the neoplasm is confined within the thyroid and thyroidectomy with dissection of the central lymph node compartment is performed, the chance of definitive cure is high (3,10,28). Therefore, early detection of MTC is crucial to perform the best surgical approach before extrathyroidal dissemination and to save the patient's life.…”

“…Actually, two diagnostic tools are available for the evaluation of patients with NTD, including those with MTC: FNAC and measurement of human C t concentrations. Previous European studies recruiting large series of patients with NTD (6)(7)(8)(9)(10)(11)(12) demonstrated that it is possible to diagnose MTC earlier with C t screening than FNAC, particularly in patients with nodules smaller than 10 mm (microMTCs). Hence, the ETA has recommended C t screening in all subjects with NTD (13).…”

“…Several studies (6)(7)(8)(9)(10)(11)(12) on sporadic MTC have demonstrated that the earlier the diagnosis the better the prognosis of MTC. C t has been shown to represent a sensitive marker for MTC, leading to the early diagnosis of the neoplasm even when fine needle aspiration cytology (FNAC) discloses benign features (as occurs in nodules smaller than 10 mm).…”