Endocrine Abstracts

Background: Screening serum calcitonin (sCT) measurement in patients with thyroid nodules is still debated. Moreover, sCt cutoffs for medullary thyroid carcinoma (MTC) are not univocally defined. Also, sensitivity of cytology by fine needle aspiration biopsy (FNAb) has been demonstrated to detect approximately half of MTCs. Ct measurement in fine-needle aspiration washout fluid (Ct-FNAb) has high sensitivity and specificity and is helpful in case of non-diagnostic cytology¹. Recently, a series oflow sCt MTC has been collected².

Aim: The objectives of this retrospective observational study were to define Ct-FNAb levels in subjects with low sCt (below cutoffs diagnostic for MTC) and to evaluate their clinical, ultrasonographic (US), cytological and histological characteristics.

Methods: We selected subjects with sCt above local normal ranges but below one of the diagnostic cutoff proposed for MTC (26 pg/ml in females and 68 pg/ml in males), subjected to FNAb with Ct-FNAb measurement and then thyroidectomized.

Results: Surprisingly, 50% (8/16) had MTC at histology, 19% cellular C hyperplasia (CCH) and only 31% neither MTC nor CCH. Ct-FNAb was significantly higher in MTC compared to both no MTC no CCH (2001 vs 25.32 ± 55.72 pg/ml; P = 0.013) and to CCH (2001 vs 195.56 ± 286.09 pg/ml; P = 0.008). Even if below the diagnostic cutoff, also sCt was higher in MTC compared to no CCH and no MTC group (19 ± 7 vs 9 ± 4 pg/ml; P = 0.019) but was not able to discriminate MTC from CCH. US failed to identify suspicious nodules, since MTC differed only for being solid and not haloed. At cytology nearly 90% of MTC lesions were non-diagnostic or, mainly, indeterminate. At histology, 7/8 were low risk micro MTCs.

Conclusion: HighCt-FNAb despite sCt only slightly elevated suggests: i) early detection of MTC before the onset of high secretion of Ct, ii) a peculiar variant of MTC, able to produce Ct but not to secrete it in bloodstream because of intracellular secretory pathway alteration, iii) possible methodological interferences in the dosage of sCt. In conclusion, this study demonstrates the importance of Ct-FNAb to discover early stages of MTC with sCt below diagnostic cutoffs.

References

1. Diazzi C et al. The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer. Endocr Pract 2013 19 769–779.

2. Gambardella C et al. Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma? BMC Endocr Disord. 2019 19 45.