Calcitonin Measurement Research Articles

Breast metastasis from medullary thyroid carcinoma: a report of a case

BackgroundMetastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.Case presentationA 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.ConclusionAlthough breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

Correction factor between two calcitonin assays: DiaSorin LiaisonXL and Cobas E601

Abstract Introduction: Calcitonin measurement is important for the diagnosis and monitoring of medullary thyroid carcinoma. Unfortunately, in clinical practice, different detection systems assays are used in the follow-up of the patients, which can be misleading. Objective: To identify the correction factor for calcitonin measurement on two different immunoanalysers: DiaSorin-LiaisonXL (immunochemiluminescence) and CobasE601 (electro-immunochemiluminescence). Methods: We selected 89 registered CT samples (28-from men; 61-from women), that were analysed on CobasE601 with reported values between 0.5 pg/ml and 2812 pg/ml (128.5±513.98). These CT samples were selected randomly to cover as wide a range of values as possible, and represented either basal CT (n=38) or selected from CT stimulation tests (n=51). Samples were evaluated subsequently on DiaSorin-LiaisonXL. All patients gave their informed consent. Results: Between the two assays a segmented linear correlation was noted. We identified the following general linear regression equation: 1.108x+19.337 (p<0.05). The bias increased at high calcitonin values. Therefore, for a better accuracy we analysed the regression equation segmentally. A statistic difference (p<0.05) was noted for CT values ranged between 350-2600 pg/ml (n=31) on DiaSorin-LiaisonXL, for which the linear regression equation for CobasE601 becomes 1.009x+169.796. Conclusions: Calcitonin correction factors are highly important in the dynamic follow up of a patient suffering from medullary thyroid carcinoma when different detection systems assays are used to determine calcitonin. We identified the correction factors for calcitonin determination between two different frequently used chemiluminescence immunoanalysers: DiaSorin-LiaisonXL and CobasE601. However, it is strongly advisable to use the same analyser in order to establish biochemical evolution of calcitonin.

Predictive Value of Calcium Test for Preoperative Diagnosis of Medullary Thyroid Carcinoma in Patients With Moderately Elevated Basal Calcitonin

ObjectiveMedullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs. MethodsA total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses. ResultsA peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%. ConclusionHigh-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified.

The value of routine measurement of serum calcitonin on insufficient, indeterminate, and suspicious thyroid nodule cytology.

Routine calcitonin measurement in patients with nodular thyroid disease is rather controversial. The aim of this study was to evaluate the contribution of serum calcitonin measurement in the diagnostic evaluation of thyroid nodules with insufficient, indeterminate, or suspicious cytology. Out of 1668 patients who underwent thyroidectomy with the diagnosis of nodular thyroid disease and were screened, 873 patients with insufficient, indeterminate, or suspicious fine-needle aspiration biopsy results were included in the study. From the total number of patients in this study, 10 (1.1%) were diagnosed as medullary thyroid cancer (MTC) using histopathology. The calcitonin level was detected to be above the assay-specific cutoff in 23 (2.6%) patients ranging between 6.5 and 4450 pg/mL. While hypercalcitoninemia was detected in all 10 MTC patients, a false positive elevation of serum calcitonin was detected in 13 patients (1.5%). Of the MTC group, seven patients had cytology results that were suspicious for malignancy (Bethesda V), one patient’s cytology showed atypia of undetermined significance (Bethesda III), and two patient’s cytology results were suspicious for follicular neoplasm (Bethesda IV). Among the cases with non-diagnostic cytology (Bethesda I), none of the patients were diagnosed with MTC. In conclusion, routine serum calcitonin measurement can be performed in selected cases rather than in all nodular thyroid patients. While it is reasonable to perform routine calcitonin measurement in patients with Bethesda IV and Bethesda V, this measurement was not useful in Bethesda I patients. In Bethesda III patients, patient-based decisions can be made according to their calcitonin measurement.

Mildly Elevated Basal Calcitonin Level in Patients With Thyroid Goiter: Using the Calcitonin Measurement in Fine-Needle Aspirate Washout Fluid of the Healthy Lobe to Define Medullary Thyroid Cancer and Reactive C-Cell Hyperplasia

Abstract Background: Mildly elevated basal calcitonin level (bCT), that suggests a bCT increase up to 100 pg/ml, may testify either medullary thyroid carcinoma (MTC) or reactive thyroid C-cell hyperplasia (CCH). The latter is observed under many conditions such as hypercalcemia, hypergastrinemia, thyroiditis, neuroendocrine tumors (NET), renal end-stage kidney disease, obesity, and smoking. The research is aimed at analyzing the clinical significance of the calcitonin measurement in the fine needle aspiration washout fluid sample (FNA-CT) for screening certain patients with nodular thyroidopathy and elevated bCT. Patients and Methods: 70 patients with mildly elevated bCT (for women 6-100 pg/ml, for men 19-100 pg/ml) underwent ultrasound-guided FNA-CT measurement of the thyroid nodules and healthy lobe tissue. After obtaining a FNA-CT specimen, the needle was washed with 0.5 ml of saline solution. The calcitonin (CT) was measured by ECLIA (LIAISON XL). Results: There were 51 females and 19 males, with a mean age of 46.8 ± 14.4 years (range 16-81). The mean value of bCT was 23.3 ± 19 pg/ml (range: 7-86.5). According to ultrasound, 66 patients (95%) presented with thyroid nodules, in 4 cases previously identified nodes were not confirmed. The mean lesion size was 10.8 ± 4.9 mm (range: 4-26). Thyroid nodules were evaluated by FNA biopsy which revealed according to the Bethesda system category I in 6 cases, II - 44, III - 2, IV - 4, V - 6, and VI - 1. Analyzing FNA-CT results we identified 13 cases (18%) with MTC with low CT level of healthy lobe tissue (1-89.6 pg/ml) and high CT level of the lesion (>2000 pg/ml), which was confirmed by final histological examination. Low CT level from both healthy lobe and the nodule (<20 pg/ml) was observed in 10 cases, we carried out the measurement of stimulated CT to exclude the extrathyroidal CT production, which was confirmed in 1 case. All 4 patients with no nodules possessed significantly higher T-rates (1650-2000 pg/ml). The remaining 43 cases (61%) had an increased CT-level of healthy tissue (>2000 pg/ml) with a lower level from the lesion. Among these patients, the probable predisposing CCH factors were obesity - 8 cases, thyroiditis - 12, NET - 3, hypercalcemia - 3, renal kidney disease - 1, and smoking - 3. These 54 patients were kept under dynamic control. The observation period for patients - 1 year. 4 patients underwent surgical treatment, subsequently, histological examination revealed papillary thyroid cancer, follicular adenoma, colloid goiter against CCH, and CT-producing NET. Conclusion: The measurement of FNA-CT of the healthy lobe tissue may be useful to differentiate MTC and CCH, but requires new data in a major cohort of patients. The disadvantage of this study is the impossibility of CCH histological verification in the follow-up group.

Diagnosis of Medullary Thyroid Cancer During COVID-19 Pandemic, the Benefit of Using a Standardized Protocol

Introduction: The reported prevalence of malignancy in thyroid nodules ranges from 4% to approximately 10%, with a small percentage (~2-8%) being medullary thyroid cancer (MTC). During the COVID-19 pandemic, elective thyroid FNA was temporarily halted at our institution. In response to this, our institution has devised a new protocol to aid in the detection of MTC, which includes serum calcitonin measurement as a surrogate marker for potential MTC. A severely elevated calcitonin (>100 pg/mL) is considered for surgery even without FNA diagnosis. We present a case of MTC that was detected due to the adopting of this protocol during COVID-19 pandemic at the Phoenix VAMC. Case Presentation: 71 year old male with an incidentally noted 3.0 cm solid, hypoechoic nodule with internal calcification, TI-RADS category 5. TSH level was normal at 3.309 mIU/mL. The patient denied any personal or family history of thyroid cancer, MEN syndrome, radiation exposure, or compressive symptoms. Following established protocol published by our institution in clinical thyroidology we performed a serum calcitonin that came back elevated at 1515 pg/mL (normal < 10 pg/mL). Given the marked elevation in serum calcitonin levels and highly suspicious radiographic appearance of the thyroid nodule, we strongly suspected medullary thyroid cancer and elected to send him directly for total thyroidectomy without performing FNA. The patient underwent total thyroidectomy with central neck dissection. Pathology showed a 3.2 cm medullary thyroid carcinoma without extrathyroidal extension or perineural invasion. Lymphovascular invasion was present. 6/10 central comparement lymph nodes were positive for metastatic disease. Postoperative calcitonin level was 2 pg/mL. Discussion: Our patient had markedly elevated serum calcitonin levels in addition to a high-risk ultrasonographic features, which was highly suspicious for MTC. Per our COVID-19 protocol, we measured the serum calcitonin level to screen for MTC and then referred him directly to surgery without FNA given the high suspicion for MTC. By using this protocol, we were able to diagnose and treat MTC expeditiously. The measurement of serum calcitonin is still controversial in the U.S, with the ATA remaining equivocal on this method. We believe that our case can serve as a practical example that validates our institution’s use of calcitonin screening of thyroid nodules in diagnosing MTC during the COVID-19 pandemic.

Circulating pro-gastrin releasing peptide (ProGRP) in patients with medullary thyroid carcinoma.

Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI). Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys® assays on Cobas e601 platform (Roche Diagnostics). Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially. Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults.

BackgroundSerum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.MethodsSubjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).ResultsThis study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively.ConclusionSpecific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Diagnostic accuracy of routine calcitonin measurement for the detection of medullary thyroid carcinoma in the management of patients with nodular thyroid disease: a meta-analysis.

ObjectiveThe usefulness of routine calcitonin measurement for early detection of medullary thyroid carcinoma (MTC) in patients with nodular thyroid disease (NTD) has been investigated in various studies. Recently, a Cochrane review has been published on this issue, but a meta-analysis is lacking yet. Therefore, we performed this meta-analysis.MethodsWe performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of routine calcitonin measurement for detecting MTC in patients with NDT were selected. Statistics were performed by using Stata software, risk of bias was assessed using Review Manager version 5.3.ResultsSeventeen studies, involving 74,407 patients were included in the study. Meta-analysis, using the bivariate random effects model and the hierarchical summary receiver operating characteristic (HSROC) curve revealed the following pooled estimates: sensitivity 0.99 (95% CI, 0.81–1.00), specificity 0.99 (95% CI, 0.97–0.99), positive likelihood ratio (L+) 72.4 (95% CI, 32.3–162.1), and negative likelihood ratio (L−) 0.01 (95% CI, 0.00–0.23). Meta-regression analysis showed that the threshold of basal calcitonin is an independent factor, but in particular performing stimulation test is not an independent factor.ConclusionsWe showed that routine basal serum calcitonin measurement in the management of patients with thyroid nodules is valuable for the detection of MTC. However, the published cut-off values should be considered and, if applicable, the patients monitored in a wait-and-see strategy by experienced physicians to avoid overtreatment.

ENDOCRINE TUMOURS: Calcitonin in thyroid and extra-thyroid neuroendocrine neoplasms: the two-faced Janus.

An increased calcitonin serum level is suggestive of a medullary thyroid cancer (MTC), but is not pathognomonic. The possibility of false positives or other calcitonin-secreting neuroendocrine neoplasms (NENs) should be considered. Serum calcitonin levels are generally assessed by immunoradiometric and chemiluminescent assays with high sensitivity and specificity; however, slightly moderately elevated levels could be attributable to various confounding factors. Calcitonin values >100 pg/mL are strongly suspicious of malignancy, whereas in patients with moderately elevated values (10-100 pg/mL) a stimulation test may be applied to improve diagnostic accuracy. Although the standard protocol and the best gender-specific cut-offs for calcium-stimulated calcitonin are still controversial, the fold of the calcitonin increase after stimulation seems to be more reliable. Patients with MTC show stimulated calcitonin values at least three to four times higher than the basal values, whereas calcitonin-secreting NENs can be distinguished from a C-cell disease by the absence of or <two-fold response to stimulation. The measurement of calcitonin in fine-needle aspirate washout (FNA-CT) and calcitonin immunocytochemical staining from thyroid nodules are ancillary methods that may significantly improve MTC diagnosis. The present review examines the gray areas in the interpretation of calcitonin measurement in order to provide a tool to clarify the origin of calcitonin secretion and differentiate the behavior of the two-faced Janus of neuroendocrinology: intra-thyroid (MTC) and extra-th9yroid NENs.

Clinical performance of calcitonin and procalcitonin Elecsys® immunoassays in patients with medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays, CT is the main tumor marker used in the diagnosis and follow-up of MTC patients. Nonetheless, procalcitonin (PCT) has recently been proposed as a useful complementary/alternative biomarker in MTC. Our aims were to investigate the diagnostic performance of CT and PCT and their combination in the differential diagnosis between active and inactive MTC and between MTC and non-MTC thyroid diseases, respectively. Serum samples were collected from 16 patients with active (i.e. primary tumour before surgery or post-surgical recurrent disease) and 23 with inactive (i.e. complete remission) MTC, 125 patients with non-MTC benign thyroid disease and 62 patients with non-MTC thyroid cancers, respectively. Elecsys® CT and PCT measurements were simultaneously performed on the Cobas e601 platform (Roche Diagnostics, Rotkreutz, Switzerland). Both CT and PCT median values in active MTC (94pmol/L and 1.17ng/mL, respectively) were significantly higher compared with inactive MTC (0.28 and 0.06) and either benign (0.37 and 0.06) or malignant (0.28 and 0.06) non-MTC. Undetectable PCT was found in five non-MTC patients with false positive CT results. Elecsys® PCT assay is a highly sensitive and specific alternative MTC marker. At the very least it appears useful in patients with positive CT results as negative PCT values securely exclude active MTC. The availability of both markers on the same automated platform facilitates reflex or reflective strategies to refine the laboratory diagnosis.

5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine.

Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the RET proto-oncogene. In this review, we propose “5P” strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on RET mutations, MEN2 could be prevented through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in RET can enable early diagnosis of MEN2. Combining RET mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately prediction of MEN2 progression, thus facilitating implementation of personalized precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires participation of physicians, patients, family members, and related organizations. Psychological support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The “5P” strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.

Measurement of calcitonin in nodular thyroid disease approach: The experience of a tertiary centre

Measurement of calcitonin in nodular thyroid disease approach: The experience of a tertiary centre

Early diagnosis of medullary thyroid cancer in case of low serum calcitonin: Role of calcitonin measurement in fine-needle aspiration washout fluid

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

Personalized management of differentiated thyroid cancer in real life \u2013 practical guidance from a multidisciplinary panel of experts

PurposeThe standard of care for differentiated thyroid carcinoma (DTC) includes surgery, risk-adapted postoperative radioiodine therapy (RaIT), individualized thyroid hormone therapy, and follow-up for detection of patients with persistent or recurrent disease. In 2019, the nine Martinique Principles for managing thyroid cancer were developed by the American Thyroid Association, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and European Thyroid Association. In this review, we present our clinical practice recommendations with regard to implementing these principles in the diagnosis, treatment, and long-term follow-up of patients with DTC.MethodsA multidisciplinary panel of five thyroid cancer experts addressed the implementation of the Martinique Principles in routine clinical practice based on clinical experience and evidence from the literature.ResultsWe provide a suggested approach for the assessment and diagnosis of DTC in routine clinical practice, including the use of neck ultrasound, measurement of serum thyroid-stimulating hormone and calcitonin, fine-needle aspiration, cytology, and molecular imaging. Recommendations for the use of surgery (lobectomy vs. total thyroidectomy) and postoperative RaIT are also provided. Long-term follow-up with neck ultrasound and measurement of serum anti-thyroglobulin antibody and basal/stimulated thyroglobulin is standard, with 123/131I radioiodine diagnostic whole-body scans and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography suggested in selected patients. Management of metastatic DTC should involve a multidisciplinary team.ConclusionsIn routine clinical practice, the Martinique Principles should be implemented in order to optimize clinical management/outcomes of patients with DTC.

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Early thyroidectomy in multiple endocrine neoplasia: a four decade experience.

Forty years ago, physicians caring for the J-kindred, a 100+ member family with multiple endocrine neoplasia type 2A (MEN2A), hypothesized that early thyroidectomy based on measurement of the biomarker calcitonin could cure patients at risk for development of medullary thyroid carcinoma (MTC). We re-evaluated 22 family members with proven RET proto-oncogene mutations (C634G) who underwent thyroidectomy and central lymphadenectomy between 1972 and 1994 based on stimulated calcitonin abnormalities. Current disease status was evaluated by serum calcitonin measurement and neck ultrasound in 18 of the 22 prospectively screened patients. The median age of the cohort at thyroidectomy was 16.5 years (range 9-24). The median duration of follow-up at the time of examination was 40 years (range 21-43) with a median current age of 52 years (range 34-65). Fifteen of the 18 patients had no detectable serum calcitonin (<2 pg/mL). Three had detectable serum calcitonin measurements, inappropriately elevated following total thyroidectomy. None of the 16 patients imaged had an abnormal ultrasound. Survival analysis shows no MTC-related deaths in the prospectively screened patients, whereas there were many in prior generations. Early thyroidectomy based on biomarker testing has rendered 15 of 18 MEN2A patients (83%) calcitonin-free with a median follow-up period of 40 years. There have been no deaths in the prospectively screened and thyroidectomized group. We conclude that early thyroidectomy and central lymph node dissection is an effective prophylactic treatment for hereditary MTC.

MON-457 Reactive Thyroid C-Cell Hyperplasia or Medullary Thyroid Cancer in a Patient with Nodular Thyroidopathy. May the Calcitonin Measurement in Fine-Needle Aspirate Washout Fluid of the Healthy Lobe Help to Define These Conditions?

Background: Serum basal calcitonin (bCT) is used as a biomarker of medullary thyroid carcinoma (MTC) but bCT can also be elevated in patients with hypercalcemias, hypergastrinemias, thyroiditis, neuroendocrine tumors, renal end-stage kidney disease, obesity and cigarette smoking. The application of bCT and calcitonin measured in the FNA washout fluid sample (FNA-CT) for screening certain patients with nodular thyroidopathy can be controversial. Case: A 44 yo patient presented with elevated bCT level - 24pg/ml (N for male <18). He had a morbid obesity (BMI-45kg/m2) and thereby received GLP-1 receptor agonists Liraglutide 18 mg in total throughout one month. The ultrasound thyroid examination showed 2 nodules in the right lobe: 11mm and 9 mm (EU-TIRADS 2 and 4). Thyroid nodules were evaluated by fine needle aspiration biopsy (FNAB) which revealed benign colloid nodules (Bethesda II). Following the most updated ATA guidelines, to accurately diagnose MTC we performed FNA-CT measurement. The concentration from both nodules exceeded the upper reporting range of 2000 pg/ml. The patient stopped his therapy with Liraglutide and after one month of following, his bCT dropped at 18 pg/ml. He underwent a second workup with same results. We examined FNA-CT of contralateral healthy lobe and obtained 913 pg/ml. After this case, 17 patients with high-normal rate of bCT: 14 of them had a nodule (Bethesda II) and elevated FNA-CT of healthy tissue of the contralateral lobe (>2000 pg/ml) were determined in follow-up group. The remaining 3 patients with nodules (Bethesda IV-VI) and FNA-CT of healthy lobe which did not exceed bCT rate, were operated. MTC was confirmed. Discussion: Our patient had not only many factors which can occur his bCT level (obesity, smoking), but also unfavourable FNA washout results. Additionally, since in clinical studies GLP-1 receptor activation has been associated with C-cell hyperplasia (CCH), we cannot completely exclude the possible effect of this treatment on patient’s bCT level. We confronted a situation when, on the one hand, FNA-CT data indicate the MTC nature of hypercalcitoninemia, but on the other hand, decreasing bCT-level in dynamic observation is not common for MTC. FNAB of the healthy lobe and obtaining high rates of CT in the washout fluid sample allowed us to confirm the diffuse CCH process, thus to follow up these patients. CT stimulation test cannot distinguish between minimal MTC and CCH and has no reference range. The weak point of the proposed study is the lack of morphological data in the follow-up group of patients. Conclusion: It is possible to use rate of FNA-CT of the healthy lobe to differentiate between various C-cell diseases, but requires new data.

Lymph Node Metastases of Medullary Thyroid Cancer: Role of Calcitonin in the Washout Fluid of Fine-Needle Aspiration.

Introduction The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. Results From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490–15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.

Considerations for Thyroid Fine Needle Aspiration (FNA) Biopsies During the COVID-19 Pandemic

Considerations for Thyroid Fine Needle Aspiration (FNA) Biopsies During the COVID-19 Pandemic

Usefulness of Serum Calcitonin in Patients with Thyroid Nodules ≤ 1 cm Without an Indication for Fine-Needle Aspiration.

Fine-needle aspiration (FNA) is not necessary in adults with nodules ≤ 1 cm without apparent extrathyroidal extension (ETE) or lymph node (LN) involvement on ultrasonography (US). In the absence of FNA and serum calcitonin (Ctn) measurement, medullary thyroid microcarcinomas (microMTC) are not diagnosed. The aim of this prospective study was to evaluate Ctn levels in adults with a low clinical risk of MTC and nodules ≤ 1 cm without ETE or LN involvement on US. A total of 506 consecutively seen adults who had nodules with two or more suspicious features were included. Patients with elevated basal Ctn underwent a calcium stimulation test and FNA. Basal Ctn was normal in 490 patients (96.8%). In the 16 patients with elevated basal Ctn, FNA revealed MTC in only one patient and MTC was not suspected in the 15 patients with elevated basal Ctn. Three patients with stimulated Ctn<100 pg/ml and benign cytology were not submitted to surgery. MTC was excluded by histology in three patients with stimulated Ctn<100 pg/ml and indeterminate or suspicious cytology and in eight patients with stimulated Ctn>100 pg/ml. One patient with stimulated Ctn>100 pg/ml had MTC. Ctn was undetectable 6 months after surgery in two patients with MTC. Although uncommon, even subjects without a suspicious history and with nodules ≤ 1 cm without ETE or LN involvement on US, but with suspicious findings, can have microMTC. The measurement of Ctn permits the diagnosis of these cases.