Calcitonin Values Research Articles

Detection of early stage medullary thyroid carcinoma by measuring serum calcitonin using an electro chemiluminescence immuno-assay: A case report of a young Japanese woman with a high-risk RET mutation.

.Medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder caused by the mutation of the RET proto-oncogene, that shows nearly complete penetration. The American Thyroid Association guidelines recommend prophylactic thyroidectomy for patients with high-risk RET mutations. However, in Japan, ethical and medical issues may preclude prophylactic treatment in young patients. Hence, an early diagnosis of MTC is necessary to ensure a favorable outcome. Here, we report the case of a young Japanese girl with a high-risk RET mutation, diagnosed with very early stage MTC using serum calcitonin (Ctn) values measured using an electro chemiluminescence immuno-assay (ECLIA). The Japanese girl with a family history of MEN2 had been followed at our hospital since she was 5-mo-old. RET analysis revealed that she displayed a Cys634Gly mutation. The patient underwent annual neck ultrasonography and calcium infusion testing. When she was 8-yr-old, the Ctn level, measured using ECLIA, dramatically increased with calcium stimulation, from a baseline of 11.3 pg/mL to 333 pg/mL. She subsequently underwent total thyroidectomy and was diagnosed with stage I MTC. Detecting early stage MTC by monitoring serum Ctn measured by ECLIA, may represent a useful strategy for patients with high-risk RET mutations.

The predictive value of calcitonin in the severity and prognosis of elderly patients with severe pneumonia

Objective To analyze the value of serum calcitonin level to determine the illness severity of the elderly patients with severe pneumonia within six hours after admission and to dynamically observe the predictive value of serum PCT level change rate in different time points on the prognosis of the patients. Methods A total of one hundred and twenty olderly patients with severe pneumonia were enrolled.Within six hours after admission, the serum PCT level was detected by enzyme linked fluorescence analysis.Acute physiology and chronic health score (APACHEⅡ) were used to assess the severity of the disease.The correlation between serum PCT and APACHEⅡ score was analyzed by Pearson correlation coefficient.The receiver operating characteristic curve (ROC curve) showed the value of serum PCT level for the prognosis.Serum PCT levels were respectively monitored on the 1st, 2nd, 3rd and 5th day.Based on the prognosis outcome on twenty-first day after admission, the patients were divided into survival group and death group.The changes of serum PCT level in two groups were compared and the rate of change of serum PCT was also compared and the value of the clinical mortality of twenty-first day was assessed. Results Within six hours after admission, the level of serum PCT was positively correlated with APACHE Ⅱ score (r=0.768, P<0.05). The receiver operating characteristic curve (ROC curve) showed that the level of serum PCT was low for the predictive value on the prognosis of the patients, and the area under the curve was 0.502(t=0.915, P=0.153). All patients, there were ninty-four cases in the survival group and twenty-six cases of death group.Dynamic observation of serum PCT levels in the survival group showed a trend of gradual decline with time prolong, the level of PCT change rate was more than or equal to 50 percent within 72 hours.The level of serum PCT change rate in death group showed a gradual upward or downward trend and the change rate of PCT in seventy-two hours was less than 50%.The ROC curve showed that the rate of change of serum PCT level in seventy-two hours was better in predicting the mortality of patients on the twenty-first day, and the area under the ROC curve was 0.892(t=3.895, P=0.001). Conclusion Dynamic monitoring of serum PCT levels can be helped to assessment the prognosis of patients with sepsis and also predict the severity of the illness.The level of serum calcitonin can reflect the severity of severe pneumonia in elderly patients within six hours after admission, but can not accurately determine the prognosis of patients with severe pneumonia.Dynamic monitoring of changes in serum calcitonin level is helpful to judge the prognosis of the elderly patients with severe pneumonia and the predictive value of serum calcitonin level change rate is higher in seventy-two hours after admission. Key words: Procalcitonin; Severe pneumonia; Prognosis

A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology.

Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements.Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays.Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%).Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost.

Reference values of serum calcitonin with calcium stimulation tests by electrochemiluminescence immunoassay before/after total thyroidectomy in Japanese patients with thyroid diseases other than medullary thyroid carcinoma.

Calcitonin is a very sensitive tumor marker of medullary thyroid carcinoma (MTC). MTC patients usually have very high values of serum calcitonin that can be used to diagnose the disease. To improve the diagnostic sensitivity in family members with small MTCs and to evaluate the postoperative biochemical cure status, a calcium stimulation test is widely used. Serum calcitonin has been measured using several methods, but in Japan, only an electrochemiluminescence immunoassay (ECLIA) is currently performed to determine serum calcitonin. Reference values for the calcium stimulation test using an ECLIA have not been reported. Here we conducted a calcium stimulation tests in 26 patients without MTC before and after total thyroidectomy. Preoperatively, the basal calcitonin values of all patients were within normal limits and increased to a mean of 14.4 pg/mL after calcium stimulation. We transformed the peak values before total thyroidectomy to a logarithmic distribution and calculated the normalized mean ± 1.96× standard deviation; the reference upper limit was thus expressed. In the female patients with non-MTC, the reference upper limit was 67.6 pg/mL. In all patients, the calcium stimulation test results after total thyroidectomy showed undetectable basal and stimulated calcitonin values (<0.5 pg/mL). This is the first study to determine reference values to be used for the calcium stimulation test along with an ECLIA in non-MTC patients. We propose that female patients are regarded as biochemically cured or normal when the stimulated calcitonin values by ECLIA are <67.6 pg/mL before surgery and <0.5 pg/mL after total thyroidectomy.

Genetic and Clinical Features of Medullary Thyroid Carcinoma: The Experience of a Single Center in Costa Rica

Background. Activating mutations in the RET gene leads to medullary thyroid carcinoma (MTC). Guidelines encourage performing RET analysis in subjects with hereditary and sporadic disease. Materials and Methods. Design. Observational, case series report study. Patients. Subjects diagnosed with MTC, with a thyroidectomy performed in a single center in Costa Rica between the years 2006 and 2015. Diagnosis and Follow-Up. Pre- and postoperative calcitonin, RET mutation, and neck ultrasound and tomography were obtained. Results. 21 subjects with histological diagnosis of MTC were followed up. The average age at diagnosis was 52.0 ± 15.7 years. The preoperative mean value of calcitonin was 1340 ± 665 pg/mL. Evidence of RET mutation was found in 26.3% of the patients, with only 2 of them grouped in the same kindred. We found statistically significant differences in mean ages between mutated (38.4 ± 20.2 y) versus nonmutated RET gene (54.6 ± 11.8 y, p = 0.04). There were no significant differences regarding tumor size, metastases, and surgical reintervention. Conclusions. We report the results of RET mutation analysis in subjects with MTC in a single center of Costa Rica. The availability of this tool increases the probability of identifying familial MTC, with the benefit of detecting affected subjects and their relatives at an earlier age.

Association of calcium-stimulated calcitonin values with pathological findings following total thyroidectomy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cervical lymph node metastasis in medullary thyroid carcinoma

To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). Cervical lymph node metastasis of medullary thyroid carcinoma is higher. Central compartment dissection is necessary in cN0 patients with extracapsular spread. Neck dissection from level II to level VII was necessary in cN+ patients. Preoperative value of calcitonin maybe can predict the lateral neck metastasis incidence.

LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations.

AimsTo report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization.MethodsThe ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high risk of cardiovascular disease at 410 centres worldwide. People with baseline serum calcitonin ≤50 ng/l were randomized to liraglutide once daily or placebo and will be followed for up to 5 years. Serum calcitonin was measured at baseline and will be measured annually thereafter. An independent committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations ≥20 ng/l.ResultsThe mean age of participants was 64.3 ± 7.2 years, 64.3% were men, and mean the body mass index was 32.5 ± 6.3 kg/m2. The median (interquartile range) baseline serum calcitonin values were 3.9 (1.0 to >7.6) ng/l in men and 1.0 (1.0 to >1) ng/l in women. Serum calcitonin was >10 ng/l in 14.6% of men and in 0.96% of women. In sex-specific multivariable linear analysis of covariance models, a reduced glomerular filtration rate (GFR) was associated with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m2 decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men.ConclusionsIn the LEADER population, the prevalence of elevated serum calcitonin concentrations at baseline was high, and there was an inverse association between eGFR and serum calcitonin concentrations.

Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature.

Generally, calcitonin (CT) values below the upper reference limit rule-out medullary thyroid carcinoma (MTC) with very high accuracy. However, sparse cases of serum-calcitonin-negative MTC (CT-NEG-MTC) have been reported. Here we reviewed CT-NEG-MTC reported in literature, discussed the potential causes and proposed a practical laboratory and clinical approach. A comprehensive literature search was conducted by using the terms "medullary thyroid carcinoma" AND "non-secreting calcitonin" OR "undetectable calcitonin". The search was updated until December 2014. Original articles that described CT-NEG-MTC were eligible for inclusion. Only MTC cases with preoperative CT below the upper reference limit were included in the present review. Eleven papers with 18 CT-NEG-MTC cases (age 50 years, size 26 mm) were retrieved. Four patients with poorly differentiated MTC died within 3 years. Different CT assays were employed and different reference values were adopted. Preoperative serum CT values were below the institution cut-off levels in all cases, and undetectable in four patients. In some papers negative CT results were confirmed by additional tests. Further laboratory investigations were performed in some of the included studies. In patients with well founded suspicious of MTC and within the reference limits/undetectable CT other laboratory investigations [carcinoembryonic antigen (CEA), procalcitonin, CT stimulation, CT in washout of nodule's aspiration] have to be performed. Surgical approach to CT-NEG-MTC does not differ from those secreting CT. Postoperative follow-up of these rare cases should include periodical imaging and measurement of all potential markers. Patients with poorly differentiated MTC are at higher risk of disease-related death, and require more aggressive follow-up strategy.

Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the thyroid C cells producing mainly calcitonin (CTN) used as tumor marker. MTC occurs either sporadic (75%) or in a hereditary form (multiple endocrine neoplasia type 2, MEN2), due to germline mutations in the RET proto-oncogene. The discovery of an MTC in a patient has several diagnostic implications involving a specific strategy: preoperative evaluation of the tumor marker CTN and the extent of the disease, classification of MTC as sporadic or hereditary by DNA testing, and screening for associated endocrinopathies in hereditary MTC. Elevated CTN is a highly sensitive and specific tumor marker for diagnosis and follow-up of MTC. CTN is directly related to the tumor mass. In patients with nodular thyroid disease, diagnosis of MTC could be made by CTN determination as an indicator of tumor burden in conjunction with fine-needle aspiration. Patients with confirmed sporadic or hereditary MTC should have a total thyroidectomy and depending on the preoperative CTN value and the extent of disease additional dissection of the lymph nodes in the central and lateral neck compartment. In MEN 2 patients diagnosed by screening, the time of prophylactic thyroidectomy depends on RET mutation and CTN level.

Calcitonin as Biomarker for the Medullary Thyroid Carcinoma.

Calcitonin (CTN) is a polypeptide hormone consisting of 32 amino acids with a disulfide bridge between position 1 and 7 that is mainly produced by the C-cells of thyroid gland. The measurement of CTN concentrations in blood reflects C-cell activity and is performed in general by immunoassay methods. However, there are analytical, physiological, pharmacological, and pathological factors that can influence results of serum CTN values. Due to the influence of these factors, there is a high variability in assay-dependent cutoffs used to discriminate between MTC, C-cell hyperplasia (CCH), and the absence of the pathological impairment of C-cells. There is a lot of evidence that the measurement of serum CTN concentrations in patients with thyroid nodules can lead to an earlier diagnosis of MTC or CCH than the exclusive use of imaging procedures and/or fine-needle aspiration cytology. Basal CTN concentrations higher than 60-100pg/mL are highly indicative for the diagnosis MTC. In the range between cutoff and 60pg/mL CTN, both MTC and HCC may be a relevant diagnosis. PCT and CTN appear to have a comparable diagnostic capability to diagnose MTCs. However, "positive" PCT values of more than 50pg/mL may be reached also in subclinical infections and will lead, therefore, to an overdiagnosis of the tumor. Pentagastrin- or calcium-stimulated serum CTN concentrations higher than cutoff values might improve diagnostics of MTC, but the non-availability of the first and the lacking of relevant cutoff values for the second tool favors the use of only basal values currently.

Ultrasound features of medullary thyroid carcinoma correlate with cancer aggressiveness: a retrospective multicenter study.

BackgroundPoor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported.MethodsStudy group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in “at risk for malignancy” (m-MTC) or “probably benign” (b-MTC) lesions.ResultsEighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1–14.4). Mean postsurgical calcitonin values were 224 ± 64 pg/ml in m-MTC and 51 ± 21 in b-MTC (p = 0.003).ConclusionsThis study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach.

Influence of thyrotropin and thyroid volume on basal serum calcitonin.

Thyroid volume was found to be a determinant of serum calcitonin levels in animal models and in thyroid-healthy subjects, as recently reported. This study aims to evaluate if this finding is confirmed in patients undergoing ultrasonography-guided fine-needle aspiration cytology of suspicious thyroid nodules. A dataset of 561 patients including basal serum FT4, FT3, TSH, calcitonin, thyroid volume, anti-thyroperoxidase antibodies (TPOAb), and cytology report, was retrospectively analysed. The median thyroid volume was 20.5 ml (14.5-26.8) in males and 12.0 ml (9.3-17.0) in females (p<0.001). The overall median serum calcitonin value was 2.00 pg/ml (2.00-3.10). A Spearman's correlation was performed between serum calcitonin levels and thyroid volume, showing a weak direct relationship (rs=0.173, p<0.001). This relationship is confirmed both in the smokers group (rs=0.337, p=0.003) and in non-smokers group (rs=0.115, p=0.012), and both in the TPOAb-positive patients (rs=0.419, p<0.001) and negative ones (rs=0.107, p=0.025). There is no correlation between serum TSH and calcitonin levels. In patients grouped according to morphologic diagnosis, calcitonin levels are slightly higher in the high-volume groups: the interquartile range was 2.00-2.00 pg/ml in the atrophy, 2.00-2.82 pg/ml in the normal volume, and 2.00-3.85 pg/ml in the goiter group (p=0.02). When males and females are computed separately, the statistical significance is lost. In conclusion, thyroid volume can mildly influence calcitonin levels. Gender acts as a "surrogate marker" of thyroid volume and the application of a gender-specific cut-off can probably overcome this issue in clinical practice.

Clinical value of [18F]FDG-PET/CT in the detection of metastatic medullary thyroid cancer

PurposeTo evaluate the value of fluorine-18 2-deoxy-2-d-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) in the detection of metastatic medullary thyroid cancer. MethodsFrom November 2006 to November 2012, 50 medullary thyroid cancer patients (median age 48.7years, range 18–76) who had a total thyroidectomy operation underwent whole-body [18F]FDG-PET/CT scans. The diagnostic accuracy of [18F]FDG-PET/CT was determined through both lesion-based and patient-based analyses. Further pathological tests were performed on all identified lesions or clinically followed for a minimum period of 6months. ResultsOne hundred forty-four suspicious lesions were identified by organ-based analysis. Of these lesions, [18F]FDG-PET/CT detected 99 true-positive lesions, sensitivity was 73.3%, and specificity was 66.7%. On the patient-based analysis, the overall sensitivity and specificity were calculated as 65.7% and 92.3%, respectively. Using a cutoff calcitonin value of 1000pg/ml, in patients with calcitonin lower than this value, sensitivity and specificity were 42.9% and 91.0%, respectively. In patients with calcitonin exceeding this value, they raised to 77.3% (χ2=4.392, P<.05) and 100% (χ2=0.197, P>.05), respectively. Compared with conventional imaging modality, PET/CT scans detected more lesions in 10 patients (20.4%) and correctly changed the treatment in 8 patients (16.3%). Conclusion[18F]FDG-PET/CT has excellent sensitivity and specificity, especially when the calcitonin value is higher than 1000pg/ml for detecting metastatic medullary thyroid cancer. Compared to conventional morphologic imaging methods, it provides additional information for diagnosis.

Ultrasound features of medullary thyroid carcinoma correlate with cancer aggressiveness: a retrospective multicenter study

Poor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported. Study group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in “at risk for malignancy” (m-MTC) or “probably benign” (b-MTC) lesions. Eighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1–14.4). Mean postsurgical calcitonin values were 224 – 64 pg/ml in m-MTC and 51 – 21 in b-MTC (p = 0.003). This study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach.

Clinical diagnosis and treatment of familial medullary thyroid carcinoma caused by a p.C618Y RET proto-oncogene mutation in a Chinese pedigree

To explore the clinical characteristics, therapeutic and clinical significance for RET proto-oncogene screening in a pedigree with familial medullary thyroid carcinoma. Comprehensive medical history was obtained from 19 members in a 4-generate southern Chinese family. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening. RET screening showed heterozygous missense mutations of TGC to TAC at codon 618 on exon 10 in 8 cases (p.C618Y) completely consistent with the clinical manifestations. The clinical data of 7 patients with medullary thyroid carcinoma (MTC) and 2 carriers of asymptomatic RET mutation from were analyzed. Single/bilateral multi-centric MTC with lymph node metastases was confirmed in 6 cases by histopathology and 1 case by clinical examination. There were 1 male and 6 females with an initial mean diagnostic age was 49.6 years (range: 24 - 78). All had palpable neck masses. And the mean maximum diameter of MTC was 2.6 cm (range 1.4 - 4.4). Seven patients underwent thyroidectomy except a 78-year-old female patient: right total and left subtotal thyroidectomy (n = 1), right total thyroidectomy (previous left total thyroidectomy for benign mass) (n = 1) and total thyroidectomy (n = 4) were performed. All procedures were accompanied by at least bilateral level VI lymph node dissection and/or with modified single/bilateral neck dissection. After the first operation, 6 patients still presented a high value of calcitonin: 1 patient died of metastasis 64 months postoperatively; 3 patients underwent reoperation at 6 months after initial operation, the calcitonin levels dropped to normal in 2/3 cases and stayed higher in 1 case; another two cases presented bilateral thyroid gland residua, local lymph node enlargement on imaging examination and elevated levels of calcitonin at 214 and 60 months postoperation respectively. However, 1/2 asymptomatic with elevated pre-operative calcitonin subjects underwent total thyroidectomy and histopathological examination showed bilateral C cell hyperplasia. The other carriers, without surgery, with normal neck images, close monitoring and a 10-month follow-up, still presented undetectable calcitonin. Based on family survey, integrated RET screening and serum levels of calcitonin facilitate an early diagnosis and normalize surgery to improve the prognosis. For asymptomatic RET mutation carriers, their levels of calcitonin shall guide the individualized regimen of prophylactic thyroidectomy or strict monitoring and follow-ups.

Early changes in carcinoembryonic antigen but not in calcitonin levels are correlated with the progression-free survival in medullary thyroid carcinoma patients treated with cytotoxic chemotherapy

The prognostic value of serum calcitonin (CT) and carcinoembryonic antigen (CEA) doubling time has been recently demonstrated in medullary thyroid carcinoma (MTC) patients. No study has yet validated the surrogate role of these markers for survival during treatment. The aim of this study was to evaluate, in patients with advanced MTC treated with cytotoxic chemotherapy, the relationship between early changes of serum CT or CEA levels and progression-free survival (PFS). The files of 28 consecutive metastatic MTC patients with progressive disease, treated with cytotoxic chemotherapy in a single tertiary referral center between 2000 and 2010, were retrospectively reviewed. Serum CT and CEA measurements and radiological Response Evaluation Criteria in Solid Tumors (RECIST) evaluations were collected every 3 months. The relationship between changes in serum CT and CEA levels at 3 months, defined by an increase or a decrease of at least 20%, and PFS according to RECIST 1.0, was estimated using Kaplan-Meier curves and log-rank test. The median follow-up for the 28 patients was 68 months. According to RECIST, a partial response, a stabilization or a progression was observed in 14, 43, and 43% of cases respectively. Median PFS from the initiation of cytotoxic chemotherapy was 4.5 months. Median PFS among patients with and without significant CT increase at 3 months was 4.6 and 3.3 months respectively (P=0.75). Median PFS among patients with a significant CEA increase at 3 months was 2.7 months, whereas it was 19.1 months in patients in whom CEA did not increase (P=0.02). At 3 months, an increase of serum CEA but not of CT levels appears as a valuable surrogate marker of short PFS in MTC patients treated with cytotoxic chemotherapy. A prospective validation is expected.

Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test

AimTo evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. Material and methodsWe performed a retrospective study of 31 consecutive cases from February 2001 to October 2007 of 17 women and 14 men, mean age 56.2 years (range: 26–88), with anatomical-pathology diagnosis of MTC and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60min after intravenous injection of 333–434 MBq of 18F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 months–8 years). ResultsSensitivity was 88%, specificity 84.6%, positive predictive value (PPV) 88%, negative predictive value (NPV) 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's t-test between positive PET studies for the disease and negative ones. No significant differences were found (p=0.3). ConclusionsIn patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients.

Correlation between Calcitonin Levels and [F18]FDG-PET/CT in the Detection of Recurrence in Patients with Sporadic and Hereditary Medullary Thyroid Cancer

Purpose. Measurement of serum calcitonin is important in the followup of patients with medullary thyroid carcinoma (MTC) and reliably reflects the presence of the disease. This is the largest study so far in bibliography investigating the diagnostic accuracy of combined [18F]FDG-PET/CT in patients with MTC and elevated calcitonin levels. Methods. Between February 2007 and February 2011, 59 [18F]FDG-PET/CT were performed on 51 patients with MTC and elevated calcitonin levels for localization of recurrent disease. Conventional morphologic imaging methods were negative or showed equivocal findings. Results. Among the 59 [18F]FDG-PET/CT, 29 were positive (26 had true-positive and 3 false-positive findings) and 30 negative. The overall per-patient sensitivity of [18F]FDG-PET/CT was 44.1%. Using as cut-off point the calcitonin value of 1000 pg/ml, in patients with calcitonin exceeding this value, sensitivity raised to 86.7%. The overall sensitivity of [18F]FDG-PET/CT was lower (23%) in patients with MEN IIA syndrome. Conclusion. The findings of this paper show that [18F]FDG-PET/CT is valuable for the detection of recurrence in patients with highly elevated calcitonin levels, >1000 pg/mL, but in patients with lower calcitonin levels, its contribution is questionable. Also, there is evidence that the sensitivity of [18F]FDG-PET/CT is lower in patients with MTC as part of MEN IIA syndrome.

Evaluación de la eficacia y del impacto clínico de la PET-18F-FDG en el diagnóstico de recurrencia del carcinoma medular de tiroides con calcitonina elevada y pruebas de imagen negativas

AimTo evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. Material and methodsWe performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60minutes after intravenous injection of 333-434 MBq of 18F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years) ResultsSensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's «t» test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3). ConclusionsIn patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients.