Basal and Calcium-Stimulated Procalcitonin for the Diagnosis of Medullary Thyroid Cancer: Lights and Shadows

Abstract Background: procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics. Methods: serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions underwent a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease. Results: median bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2=0.75), and with tumor size (P<0.01, R2=0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 98.2%, negative predictive value [NPV]: 90.6%, P<0.01). While bproCt was >0.07 ng/ml in 38/39 (97.4%) patients with MTC >10 mm, it was only above said cut-off in 15/23 (65.2%) patients with tumors ≤10 mm. A sproCt >0.19 ng/ml was able to identify MTC (sensitivity: 90.0%, specificity:100.0%, PPV: 100.0%, NPV: 86.7% [P<0.01]). Conclusions: proCt cannot replace Ct as the standard of care in the MTC diagnosis, because it often fails to identify a small MTC. That said, it has a very high specificity and can be used in combination with Ct in MTC diagnostics, particularly in the case of mildly elevated basal Ct levels.

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Basal and Calcium-Stimulated Procalcitonin for the Diagnosis of Medullary Thyroid Cancers: Lights and Shadows

Frontiers in Endocrinology ◽

10.3389/fendo.2021.754565 ◽

2021 ◽

Vol 12 ◽

Author(s):

Simona Censi ◽

Marta Di Stefano ◽

Andrea Repaci ◽

Teresa Benvenuti ◽

Jacopo Manso ◽

...

Keyword(s):

Thyroid Cancer ◽

Positive Predictive Value ◽

Predictive Value ◽

Medullary Thyroid Cancer ◽

High Specificity ◽

Final Diagnosis ◽

Tertiary Level ◽

Consecutive Series ◽

Medullary Thyroid ◽

Calcium Stimulation

BackgroundProcalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics.MethodsSerum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions undergoing a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease.ResultsMedian bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2 = 0.75), and with tumor size (P<0.01, R2 = 0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 98.2%, negative predictive value [NPV]: 90.6%, P<0.01). While bproCt was >0.07 ng/ml in 38/39 (97.4%) patients with MTC >10 mm, it was above said cut-off only in 15/23 (65.2%) patients with tumors ≤10 mm. A sproCt >0.19 ng/ml was able to identify MTC [sensitivity: 90.0%, specificity:100.0%, PPV: 100.0%, NPV: 86.7% (P<0.01)].ConclusionsOur data suggest that bproCt can be a good adjunct to Ct for MTC diagnostic purposes. In consideration of its high specificity, it can be used in combination with Ct in MTC diagnostics, particularly in the case of mildly elevated basal Ct levels.

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Abstract #1101 The Value of Calcitonin Calcium Stimulation Test Levels as Predictors of Medullary Thyroid Cancer.

Endocrine Practice ◽

10.1016/s1530-891x(20)47466-x ◽

2018 ◽

Vol 24 ◽

pp. 273-274

Author(s):

Corin Badiu ◽

Mara Baet ◽

Ruxandra Dobrescu ◽

Andra Caragheorgheopol ◽

Corneci Cristina

Keyword(s):

Thyroid Cancer ◽

Medullary Thyroid Cancer ◽

Stimulation Test ◽

Medullary Thyroid ◽

Calcium Stimulation

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Localization of CaSR Antagonists in CaSR-expressing Medullary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-1756 ◽

2013 ◽

Vol 98 (11) ◽

pp. E1722-E1729 ◽

Cited By ~ 4

Author(s):

Haiming Ding ◽

Adlina Mohd Yusof ◽

Shankaran Kothandaraman ◽

Motoyasu Saji ◽

Chaojie Wang ◽

...

Keyword(s):

Thyroid Cancer ◽

Nude Mice ◽

Medullary Thyroid Cancer ◽

Antagonistic Activity ◽

Parathyroid Glands ◽

Human Embryonic Kidney Cells ◽

Medullary Thyroid ◽

Calcium Stimulation

Objective: Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo. Design: We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was further radiolabeled with 125I and evaluated in nude mice with and without heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do not express CaSR, respectively. Results: Two newly synthesized compounds, 9 and 11, exhibited better antagonistic activity than Calhex 231. The half-life of 125I-compound 9 in nude mice without xenografts was 9.9 hours. A biodistribution study in nude mice bearing both tumors demonstrated that the uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24 hours: 0.39 ± 0.24 vs 0.18 ± 0.12 percentage of injected dose per gram of tissue (%ID/g) (P = .002), with a ratio of 2.25 ± 0.62. Tumor-to-background ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to-blood values increased from 2.02 ± 0.52 at 1 hour to 3.29 ± 0.98 at 24 hour (P = .015) for TT tumors, and 1.7 ± 0.56 at 1 hour to 1.48 ± 0.33 at 24 hour (P = .36) for MZ-CRC-1 tumors. Conclusions: Our new CaSR antagonists specifically inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors in vivo, and therefore have the potential to serve as scaffolds for further development as imaging pharmaceuticals.

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Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Endocrine Related Cancer ◽

10.1677/erc-06-0053 ◽

2007 ◽

Vol 14 (2) ◽

pp. 393-403 ◽

Cited By ~ 22

Author(s):

Uberta Verga ◽

Stefano Ferrero ◽

Leonardo Vicentini ◽

Tatiana Brambilla ◽

Valentina Cirello ◽

...

Keyword(s):

Thyroid Cancer ◽

Multinodular Goiter ◽

Medullary Thyroid Cancer ◽

Final Diagnosis ◽

C Cells ◽

Cell Hyperplasia ◽

Medullary Thyroid ◽

C Cell Hyperplasia ◽

C Cell ◽

Molecular Studies

The cut-off values able to differentiate between reactive or neoplastic C-cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). In the present study, the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml were studied. As controls, 16 patients with MNG and bCT levels <10 pg/ml and 4 patients with familial (FMTC) were included. For each case, calcitonin (CT) immunoreactive cells were counted in 60 consecutive high-power fields (400×) and CCH classified as focal, diffuse, nodular, or neoplastic. RET genetic analyses were performed at the germline and tissue levels in MTC and CCH cases. In patients with MNG, sCT levels >50 pg/ml were associated with CCH or MTC, being the total number of C-cells/60 fields significantly higher than that found in MNG with normal bCT (P = 0.0008) and comparable with that detected in FMTCs. In the group with sCT>50 pg/ml, the C-cells displayed a neoplastic phenotype. Neither germline nor somatic RET mutations were found. In conclusion, sCT levels >50 pg/ml were always associated with CCH, without correlation between CT levels and the number of C-cells or the final diagnosis. The C-cells had a morphology and distribution pattern similar to those observed in FMTC. Thus, sCT levels >50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a prophylactic surgical treatment.

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Calcitonin level in the postoperative period as a risk factor for persistence of medular thyroid cancer

Clinical endocrinology and endocrine surgery ◽

10.30978/cees-2021-4-9 ◽

2021 ◽

pp. 9-18

Author(s):

O. A. Tovkai ◽

V. O. Palamarchuk ◽

V. A. Smolyar ◽

V. V. Kuts ◽

R. M. Sichinava

Keyword(s):

Thyroid Cancer ◽

Surgical Treatment ◽

Postoperative Period ◽

Predictive Value ◽

Medullary Thyroid Cancer ◽

Disease Stage ◽

Clinical Recurrence ◽

Medullary Thyroid ◽

Group 1

Aim — to evaluate the possibility of using basal calcitonin levels in the postoperative period to assess the effectiveness of surgical treatment of medullary thyroid cancer and the likelihood of its persistence (recurrence). Materials and methods. A single-site retrospective study was conducted to assess results of surgical treatment of 194 patients (74.2 % women and 25.8 % men), from them148 (76.3 %) patients had primary forms of the disease (group 1) and 46 (23.8 %) the recurrent form (group 2). Primary surgery included thyroidectomy, supplemented with thecentral and lateral dissection of the neck. Patients in group 1 were divided into two subgroups depending on the postoperative calcitoninlevels: group 1A with normal calcitonin levels (≤ 18 pg/ml)and group 1B with hypercalcitoninemia (> 18 pg/ml). The quantitativedetermination of blood serum calcitonin levels was performed using automatic immunochemiluminescent analyzer «MAGLUMI» («Snibe Diagnostic», China) in 1 week and 1 year after surgery. Accumulation and primary data processing were performed in MS Excel 2013, statistical processing was performed using StatPlus programs with descriptive statistics, parametric and nonparametric methods for testing statistical hypotheses (Student’s criteria, Mann-Whitney, Fisher angular transformation), analysis of conjugation tables, ROC-analysis. The results were considered statistically significantat p < 0.05. Results. The average duration of follow-up was 67.5 months. The results of surgery were analyzed in terms of absence or presence of clinical recurrence, calcitoninlevels in the early postoperative period (5 days) were used as a predictor. After 2 years of follow-up,normocalcitoninemiawas accompanied by recurrence in almost 2 % of cases, while hypercalcitoninemia — in 61 % to 74 %, depending on the stage and frequency of the disease. The correlationsbetween postoperative calcitonin levels and presence of recurrence (persistence) of medullary thyroid cancer has been established: AUC = 0.928 (0.867; 0.989, Juden index (J) = 0.429, threshold (cut-off point) ≥ 28.1 pg/ml, sensitivity = 0.938 (0.854; 1,000), specificity = 0.855 (0.789; 0.920), predictive value of positive result(PPV) = 0.699, predictive value of negative resultPNV = 0.991. Moreover, countersensitivity scores and incidence of negative test results in patients with relapse depending on the level of postoperative calcitonin were calculated. Conclusions. Postoperative calcitonin levels in 5 days after surgery can be used for assessment of efficacy of the surgical treatment (AUC — 0,928 (0,867; 0,989), Juden index — 0,429)). The prognosis of recurrence-free disease does not depend on the disease stage. At calcitonin levels < 18 pg/ml, clinical signs of the disease persistence (recurrence) were detected in 1.5 % of cases (PNV = 0.991). The reliability of predicting the disease recurrence depended on the stage and frequency of surgery: PRV = 0.612 in primary forms without metastases, PRV = 0.825 in recurrent forms. Calcitonin values < 28.1 pg/ml can be considered a relatively «safe» level.

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Intraoperative and postoperative care of unsuspected pheochromocytoma in medullary thyroid cancer

Otolaryngology ◽

10.1016/s0194-5998(94)70538-0 ◽

1994 ◽

Vol 111 (5) ◽

pp. 665-668

Author(s):

S YEE ◽

S STERN

Keyword(s):

Thyroid Cancer ◽

Postoperative Care ◽

Medullary Thyroid Cancer ◽

Medullary Thyroid

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Immunoscintigraphy in Medullary Thyroid Cancer Using an 123I- or 111ln-Labelled Monoclonal Anti-CEA Antibody Fragment

Nuklearmedizin ◽

10.1055/s-0038-1624348 ◽

1986 ◽

Vol 25 (06) ◽

pp. 227-231 ◽

Cited By ~ 6

Author(s):

Chr. Eilles ◽

W. Spiegel ◽

W. Becker ◽

W. Börner ◽

Chr. Reiners

Keyword(s):

Bone Marrow ◽

Thyroid Cancer ◽

Potassium Iodide ◽

Medullary Thyroid Cancer ◽

Elevated Serum ◽

Antibody Fragment ◽

Special Importance ◽

Medullary Thyroid ◽

Medullary Cancer ◽

Serum Cea

The monoclonal anti-CEA F(ab’)2 fragment MAb BW 431/31, labelled with 123I or111 In, was used for immunoscintigraphy (IS) in 9 patients with medullary cancer of the thyroid (CCC). The results of 11 studies lead to the following conclusions: 1) When using radioiodine as a label for MAb in IS, potassium iodide is absolutely necessary to block the thyroid which is of special importance in patients with thyroid cancer; 2) Preinjection of “cold” MAb reduces the relatively high unspecific uptake (especially in bone marrow) of MAb BW 431/31, which is of special importance for the antibody labelled with 111 In; 3) IS with MAb BW 413/31 in patients with CCC and elevated serum CEA is positive only in cases with large secondaries; and 4) In patients with CCC and several manifestations of secondaries, only a single (large) metastasis may be apparent.

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