Follow-up Of Medullary Thyroid Cancer Research Articles

The role of procalcitonin in the follow-up of medullary thyroid cancer.

Calcitonin (Ct) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. We analyzed the performance of procalcitonin (ProCt) in follow-up MTC patients. In this monocentric and retrospective study, we consecutively obtained ProCt and Ct values from all MTC patients that we visited during the period from April 2021 to May 2022. Patients were defined as having structural evidence of disease (29/90, 32.2%) irrespective of Ct values or, in its absence, as not evident disease (NED) if Ct was ≤10 ng/L (47/90, 52.2%), or minimal residual disease if Ct was >10 ng/L (14/90, 15.6%). Ct and ProCt values were highly correlated (r = 0.883, P < 0.01). Median ProCt values differed between NED, minimal residual disease, and structural disease, being 0.04 ng/mL, 0.26 ng/mL, and 1.98 ng/mL, respectively (P < 0.01). ProCt was undetectable (<0.04 ng/mL) in 40/47 (85.1%) of NED patients, in 3/14 (21.4%) patients with minimal residual disease and in none of the patients with a structural disease (P < 0.01). Among the 11 patients with detectable but ≤10 ng/L Ct and undetectable ProCt values, none had a structural disease. The most accurate cut-off of ProCt to distinguish between the presence or absence of a structural disease was >0.12 ng/mL (P < 0.01, area under the curve: 0.963), with the following sensitivity, specificity, positive predictive value, and negative predictive value (NPV): 100%, 83.61%, 74.4%, and 100.0%. ProCt and Ct have a high correlation in MTC follow-up. ProCt may be useful as an adjunct to Ct, especially for its NPV concerning the structural disease.

Lentivirus-mediated silencing of MPHOSPH8 inhibits MTC proliferation and enhances apoptosis.

Thyroid carcinoma (TC) is the most common malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. For medullary thyroid cancer (MTC), a type of TC, a high mortality rate has been reported. In previous studies, M-phase phosphoprotein 8 (MPHOSPH8) displayed an elevated expression in various human carcinoma cells. Thus, MPHOSPH8 may be a sensitive biomarker that could be used for the diagnosis and follow-up of MTC. In the present study, plasmids of RNA interference targeting the MPHOSPH8 gene were constructed. Once these lentiviruses targeting MPHOSPH8 were transfected into the MTC cell line TT, cell viability and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was used to assess the cell cycle distribution and apoptosis. The expression levels of MPHOSPH8 were detected by reverse transcription quantitative-polymerase chain reaction and western blot analyses. Depletion of MPHOSPH8 significantly inhibited cell proliferation. Furthermore, knockdown of MPHOSPH8 in TT cells led to G0/G1 phase cell cycle arrest and apoptosis. The results of the present study suggest that MPHOSPH8 promotes cell proliferation and may be a potential target for anticancer therapy of MTC.

Refining Calcium Test for the Diagnosis of Medullary Thyroid Cancer: Cutoffs, Procedures, and Safety

Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Calcium Stimulated Calcitonin Measurement: A Procedural Proposal

Human calcitonin (hCT) is a tumor marker essential to the diagnosis and follow-up of medullary thyroid cancer (MTC). Current consensus recommends hCT measurement when initially evaluating thyroid nodules; if slightly elevated, a confirmatory stimulated calcitonin test is commonly performed, usually using pentagastrin. In recent years the supply of pentagastrin was not guaranteed with long periods of unavailability; the outlook for future availability is unknown. Therefore it is desirable for many institutions to establish a procedure for calcitonin stimulation using a stimulant with a secure supply; stimulation of calcitonin using calcium represents the easiest alternative.Several schemes and dosages have been used in the past for calcium stimulated calcitonin measurement. In this paper we propose a procedure for calcium stimulated calcitonin measurement based on our experiences. Furthermore we will briefly point out the limitations of this method with regard to available data in literature.

Serum calcitonin estimation in medullary thyroid cancer: basal or stimulated levels?

Calcitonin (Ct) is a tumour marker essential for the diagnosis and follow-up of medullary thyroid cancer (MTC). Accurate and consistent measurements of serum Ct are of critical importance. Ct measurements by different methods can differ, leading to difficulties in the interpretation of results. Second generation assays for Ct have been developed and are now available in clinical laboratories. However, the lack of standardization for Ct assays remains a common problem with Ct assays. The reference interval and reliability should be carefully defined.The role of stimulated Ct for the diagnosis and follow-up of MTC should also be pointed out as the pentagastrin test is no more available in all countries. However, the stimulated test remains very useful to exclude MTC if the basal Ct serum level is in the grey zone (15-20 ng/L), after surgery to confirm the complete cure. A residual response after surgery could indicate a need for aggressive surgery or - in case of metastatic disease - could suggest the prognosis.High-dose Ca test (2.5mg/kg) seems to be a reliable and effective test for the diagnosis and follow-up of MTC. It seems more potent than pentagastrin with fewer side effects. The threshold able to discriminate healthy subjects from C-cell hyperplasia (CCH) cases for the stimulated Ct concentration is 184 ng/L for women and 1620 ng/L for men.As stimulated Ca test will eventually replace the pentagastrin test, there is a need to confirm or to modify the threshold identified for each assay individually.

Comparison of Calcium and Pentagastrin Tests for the Diagnosis and Follow-Up of Medullary Thyroid Cancer

The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. Patients with MTC in remission (n=24) or in persistence (n=18), RET gene mutations carriers (n=14), patients with nodular goiter (n=69), and healthy volunteers (n=16) were submitted to pentagastrin and Ca (25 mg/kg) tests. In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with a mean number of 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified.

New advances in the diagnosis, medical management and follow-up of medullary thyroid cancer

Abstract Medullary thyroid cancer (MTC), which behaves more aggressively than the other well-differentiated thyroid cancers of follicular cell origin, accounts for 10% of all thyroid cancer-related deaths. Most MTCs are sporadic however approximately 25% is hereditary as part of the multiple endocrine neoplasia syndrome type 2 (MEN 2a and 2b). Both sporadic and inherited forms of MTC have a propensity for lymphatic and distant metastasis. The primary treatment of MTC is total thyroidectomy and removal of all neoplastic tissues present in the neck. After surgical treatment, measurements of serum calcitonin and carcinoembryonic antigen are of paramount importance in the postoperative follow-up since these markers reflect the presence of persistent or recurrent disease. Systemic chemotherapy with dacarbazine, 5-fluorouracil and doxorubicin, either alone or in combination, has shown very limited efficacy, producing only partial responses in the range of 10-20% and of short duration. Although current treatment options for patients with metastatic and refractory MTC are limited, recent advances in molecular oncology have fostered the invention of novel small molecules which target specific pathways which are thought to be essential in the MTC carcinogenesis. Several kinase inhibitors are currently under evaluation and preliminary results are promising. Keywords: Medullary thyroid cancer, thyrosine kinase inhibitors Ozet Meduller Tiroid Kanseri (MTC) folikul hucrelerinden kaynaklanan iyi diferansiye tiroid kanserlerinden daha agresif seyreder ve tiroid hastaliklarina bagli olusan olumlerin yaklasik %10’unu olusturur. MTC’rinin cogu sporadik olarak ortaya cikar fakat %25’i MEN Tip 2’nin bir parcasi olarak herediter olabilir. MTC’nin her 2 formunda da lenf nodu metastazi ve uzak metastaz gorulebilir. Hem sporadik hem de herediter formun primer tedavisi total tiroidektomi ve boyundaki tumor dokusunun tamaminin cikarilmasidir. Total tiroidektomi sonrasi serum CT (kalsitonin) ve CEA olcumu MTC hastalarin operasyon sonrasi takibinde onemlidir cunku bu belirteclerdeki artis persistan veya rekurren hastalik oldugunu dusundurur. Dakarbazin, 5-florourasil ve doksorubisinle (tek veya kombinasyon seklinde) sistemik kemoterapinin etkisi oldukca sinirlidir, kismi cevap %10-20 arasindadir ve kisa surelidir. Metastatik veya rekurren MTC hastalarinda gunumuzde tedavi secenekleri sinirli olmasina ragmen molekuler onkolojideki son ilerlemeler MTC tumor olusumunda onemli oldugu dusunulen spesifik yolaklara yonelik kucuk molekullerin gelisimini hizlandirmistir. Bazi kinaz inhibitorleri MTC’lerinde denenmektedir ve on sonuclar umit vericidir. Anahtar sozcukler: Meduller tiroid kanseri, tirozin kinaz inhibitorleri

Biochemical Markers in the Follow-up of Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC. Patients were divided according to the stage of disease: group 1, no evidence; group 2, stable disease (SD); and group 3, progressive disease (PD). Plasma dopamine was increased in the majority of the patients with SD and PD; however it did not correlate with extent of disease. Elevated plasma platelet levels of serotonin were only present in patients with multiple endocrine neoplasia 2 with SD or PD but did not differ between those groups. Histamine metabolites were elevated in 20% of patients with SD and PD. In addition to plasma calcitonin, only CEA and chromogranin A could differentiate between stable and progressive MTC. MTCs are capable of synthesizing catecholamines, serotonin, and histamine metabolites underscoring that MTCs have metabolic characteristics in common with other neuroendocrine tumors. Thus far, clinical usefulness and relevance seems limited. The most useful markers in the follow-up of MTC are plasma calcitonin and CEA.