Calcitonin Measurement Research Articles

Thyroglobulin and calcitonin measurements: pitfalls and future perspectives.

Thyroid cancer is the most prevalent endocrine cancer. Prognosis depends on type and stage of cancer when discovered. Treatment involves (hemi-)thyroidectomy, possibly followed by additional therapeutic options. After treatment, patients are monitored using serum concentrations of endocrine tumour marker thyroglobulin in case of differentiated cancer and calcitonin in case of medullary thyroid cancer. Measuring thyroglobulin and calcitonin concentrations in serum may be challenging. In this review we give a complete overview of the evolvement in laboratory measurements regarding thyroglobulin and calcitonin with an emphasis on (pre-)analytical challenges and potential approaches to overcome current pitfalls.

Defining the Functional Sensitivity for the Siemens Atellica Calcitonin Assay: Insight From a Single-Center Study

BackgroundDetectable, and especially rising postthyroidectomy serum calcitonin and carcinoembryonic antigen levels, as per American Thyroid Association guidelines, indicate potential disease presence, requiring frequent calcitonin measurement or imaging for early detection of persistent or recurrent medullary thyroid carcinoma. Thus, defining the clinical cutoff value of detection of calcitonin assays relative to imaging and clinical status is crucial for patient care. This study aimed to evaluate postoperative calcitonin levels using the new Siemens Atellica assay system to determine the most appropriate levels for clinical decision-making. MethodsA retrospective analysis was conducted using Siemens Atellica for calcitonin testing on 56 samples from 40 patients between September 27, 2022 and August 11, 2023. Only calcitonin results performed at least 3 months post-total thyroidectomy were included. Imaging studies, within 6 months of the calcitonin report, were assessed. Carcinoembryonic antigen results were also reviewed. ResultsPrecision analysis at 2.94 and 5.24 pg/mL revealed coefficients of variation at 16.49% and 8.87%, respectively. For the evidence of post-total thyroidectomy persistent or recurrent medullary thyroid carcinoma confirmed by imaging, using a 1.89 pg/mL cutoff for calcitonin yielded 43% sensitivity and 67% specificity. Using a 5.00 pg/mL cutoff resulted in 0% sensitivity and 100% specificity. ConclusionsOur findings indicate the potential suitability of a 5 pg/mL calcitonin cutoff on the Siemens Atellica platform for evaluating tumor persistence or recurrence in post-thyroidectomy patients in our institution. However, individual laboratories should establish their own clinical cutoff value when evaluating calcitonin levels for monitoring tumor recurrence post-thyroidectomy.

High Prevalence of Hypercalcitoninemia in a Large Cohort of Adult and Pediatric Patients With PTH Resistance Syndromes

Abstract Context Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathyroid hormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series. Objective Our aim was to investigate the characteristics of hypercalcitoninemia in pediatric and adult patients with PHP/iPPSD. Methods We retrospectively collected data from 2 cohorts from 2 European endocrinology tertiary centers: the pediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements. Results In the pediatric cohort, 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in pediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded; adult patients underwent regular thyroid ultrasound to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects, and subjects with MTC, there was no difference with patients with C-cell hyperplasia. Conclusion This study underscores the common occurrence of hypercalcitoninemia in both pediatric and adult patients with PHP/iPPSD, in particular with subtypes iPPSD2 and iPPSD3. Furthermore, these patients show hyperresponsiveness to calcium stimulation tests falling between healthy subjects and patients with MTC. These findings contribute to the understanding of CT dynamics in the context of PHP/iPPSD.

Diagnosis of medullary thyroid microcarcinoma by calcitonin measurement in fine-needle aspiration washout

Diagnosis of medullary thyroid microcarcinoma by calcitonin measurement in fine-needle aspiration washout

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

Up Date from the Factors Related to the Development of Endocrine Diseases: A perspective biological chemistry

The endocrine system contributes to the functioning of the body's metabolism, the increase or decrease in hormones favors the formation of disorders that develop metabolic diseases. Aim. Compile information on factors that intervene in the development of endocrinological diseases, mainly in hormonal action and alterations of certain metabolites. Methodology. A bib¬liographic search was carried out in Google Schoolar and PudMed using keywords, the information was analyzed in pairs. Results. Hormonal action is affected by desynchronization in hormonal production, triggering metabolic diseases. Measurement of calcium, phosphorus, PTH, 25OHD, 1.25OHD, calcitonin and osteocalcin help in the diagnosis. Conclusion. Circadian alterations favor the development of metabolic diseases, the participation of the clinical laboratory with specific tests is important.

Diffuse C-Cells Hyperplasia Is the Source of False Positive Calcitonin Measurement in FNA Washout Fluids of Thyroid Nodules: A Rational Clinical Approach to Avoiding Unnecessary Surgery.

The FNA-CT is useful for the diagnosis of MTC. The aim of this study was to evaluate the performance of FNA-CT in TNs coexisting with CCH. This study retrospectively reviewed the records of 11 patients with TNs submitted to thyroidectomy on the basis of elevated basal and/or stimulated serum CT values, which at histology were not confirmed to be MTC. The results obtained in this group were compared with those of a previously reported group of histologically proven MTC patients submitted to an identical presurgical evaluation. All patients, negative for known mutations in the RET proto-oncogene, were preoperatively submitted to neck ultrasound, FNA-cytology, and FNA-CT. Approximately 6 of 11 patients showed increased (>36 ng/mL, as established in previous studies not involving patients with CCH) FNA-CT. All these patients showed diffuse CCH at histology in the thyroid lobe submitted to FNA; 5 of them were benign at histology, while only one was malignant (papillary thyroid carcinoma, PTC). The remaining 5 of 11 patients had low FNA-CT (<36 ng/mL), and all of them showed only focal CCH in the lobe submitted to FNA; three of them were malignant (2 PTC, 1 follicular carcinoma), while two were benign. Employing the currently proposed cut-off values, false-positive FNA-CT results may be observed in benign/malignant TNs with coexisting diffuse CCH. FNA-CT must therefore be cautiously used in the diagnostic approach for patients with TNs and a slightly increased basal or stimulated serum CT concentration in order to avoid unnecessary surgery.

Evaluation of calcitonin measurement in fine needle aspirates in the diagnosis of primary and metastatic medullary thyroid carcinoma

Serum CT represents the tumoral marker of medullary thyroid carcinoma (MTC), and is a main diagnostic tool and follow-up after treatment. Nevertheless, calcitonin levels can be elevated in a number of other situations and does not always distinguish MTC from other clinical circumstances, particularly when elevation remains moderate. Fine needle aspiration biopsy is a widely used examination for the investigation of thyroid nodules and lymph nodes, but its sensitivity for the diagnosis of MTC remains low ranging from 45% to 63%. Calcitonin measurement in fine needle aspiration wash out fluid has been reported as reliable, and is recommended by the experts of American Thyroid Association (ATA) in their 2015 consensus for the management of MTC even if its diagnostic is not standardized yet. Material and methods: Twenty patients with 45 lesions (thyroid nodule and lymph node) were included in this study; calcitonin was performed in each of them, the puncture needles were washed with 1ml of saline solution to obtain to measure Calcitonin in fine needle aspiration washout fluid. Results: After surgery 32 MTC were diagnosed on histology. Receiver operating curve (ROC curve) indicated CT in fine needle aspiration &gt;22.99pg/ml as more accurate cut off value with a sensitivity and specificity of 96.87% and 100%. Calcitonin ratio was evaluated too, the cut off value being&gt;0.64 with a sensitivity of 62.5% and specificity of 100%. Conclusion: Calcitonin in fine needle aspiration wash out fluid constitutes an excellent diagnostic tool of MTC with the use of 22.99pg/ml threshold.

Measurement of calcitonin and cea in the needle washout fluid from thyroid nodule for the diagnosis of medullary thyroid carcinoma

Background. medullary thyroid carcinoma (mtc) produces serum markers including calcitonin (ct) and carcinoembryonic antigen (cea). The measurement of ct in fine-needle aspirate washout fluid (FNA-CT) improves the cytological diagnosis of mtc. However, no data are available about cut-off values for FNA-CT using currently immunoassay. The measurement of cea in the needle washout fluid (FNa-cea) in mtc has not been studied.Objective: to assess the diagnostic value and propose cut-off values for FNA-CT and FNacea in the thyroid nodule to diagnose mtc.Material and Methods. We conducted a retrospective analysis of 164 samples of fine-needle aspirate washout fluid collected from 92 patients with thyroid nodules, who underwent FNa followed by cytological examination and measurement of FNA-CT. seventeen cases with mtc and 41 with non-mtc nodules were histologically verified. one hundred and six nodules identified as non-mtc by cytology were not operated on. FNa-cea was additionally studied in 29 samples. The cut-off value was determined by Roc analysis.Results. The FNA-CT level was &gt;2000 pg/ml in all mtc nodules, except for one, in which the FNA-CT level was 638 pg/ml. In non-mtc nodules, the FNA-CT levels were &lt;10 pg/ml and &lt;100 pg/ml in 81 % and 90 %, respectively, however, it was &gt;500 pg/ml in 5 %, and &gt;1000 pg/ml in 2 %. At a cut-off value of 590 pg/ml, the sensitivity and specificity of FNA-CT were 100 % and 96 %, and at a cut-off of 1721 pg/ml, the corresponding values were 94 % and 99 %. The false positive FNA-CT values were 3.7 % and 1.2 % at the cut-off values of 590 pg/ml and 1721 pg/ml, respectively. The median levels of FNa-cea in mtc and non-mtc nodules were 59.3 ng/ml and 1.5 ng/ml, respectively. At a cut-off value of 7.5 ng/ml, the sensitivity of FNa-cea was 86 % and specificity was 100 %. Additional measurement of FNa-cea prevented all false-positive results of FNA-CT, but did not detect 2 mtcs with low FNa-cea levels (false-negative rate of 6.9 %). Among samples with FNA-CT value of &gt;590 pg/ml and negative cytology (n=9), FNa-cea differentiated mtc with 100 % sensitivity and specificity.Conclusion. The maximum sensitivity of FNA-CT in the thyroid nodule was at a cut-off value of 590 pg/ml (100 %), the maximum specificity was at a cut-off value of 1721 pg/ml (99 %). Risk of false positive result is the major challenge of FNA-CT. to reduce false-positive results, we recommend to measure FNa-cea in the nodules with negative cytology and high level of FNA-CT. At a cut-off value of 7.5 ng/ml, FNa-cea allows the false-positive FNA-CT to be excluded.

An old friend, a new insight: Calcitonin measurement in serum and aspiration needle washout fluids significantly increases the early and accurate detection of medullary thyroid cancer.

The sensitivity of cytological (CY) evaluation after fine-needle aspiration (FNA) for detecting medullary thyroid carcinoma (MTC) is a subject of controversy. The routine use of serum calcitonin (CT) in patients with thyroid nodules is not universally adopted. The authors conducted CT screening of FNA washout fluid (FNA-CT) to address the diagnostic challenges. The objective was to assess the contributions of serum CT, FNA cytology (FNA-CY), and FNA-CT to the diagnosis. Between February 2019 and June 2022 (group 1), the authors prospectively screened the CT of patients with thyroid nodules. Both FNA-CY and FNA-CT were performed for patients with persistently elevated CT values. The sensitivity of FNA-CY, serum CT, and FNA-CT for accurate diagnosis was evaluated. Additionally, the authors retrospectively examined data from patients with thyroid nodules before CT screening (2008-2019) (group 2). They compared the characteristics of MTC patients in groups 1 and 2. MTC was identified in 30 patients (0.25%) in group 1 and 19 (0.07%) in group 2. A FNA-CT cutoff value of 4085.5pg/mL detected MTC with a sensitivity of 96.8%, and a serum CT cutoff value of 28.3pg/mL detected MTC with a sensitivity of 86.7%. In contrast, FNA-CY detected MTC with a sensitivity of 42.4%. In group 1, 18 patients (60%) with MTC were diagnosed with microcarcinoma, whereas only two patients (10.5%) in group 2 had microcarcinoma. This study detected MTC earlier by routinely measuring serum CT in all patients with nodular thyroid disease and performing FNA-CT in those with elevated values. FNA-CT and serum CT sensitivities were significantly higher than those of FNA-CY. This study revealed different FNA-CT cutoff values compared to other studies, emphasizing the need for determining clinic-specific cutoff values.

Appropriate and mindful measurement of serum calcitonin in patients with thyroid nodules. A white paper

Medullary thyroid carcinoma (MTC) is an infrequent thyroid malignancy that is often diagnosed at advanced stage with consequent poor prognosis. Thus, the earlier the diagnosis of MTC, the better the prognosis. Unfortunately, the preoperative detection of MTC remains challenging in clinical practice. In fact, while ultrasound and fine-needle aspiration cytology have suboptimal performance in this context, measuring serum calcitonin (Ctn), fully recognized as the most reliable test to detect MTC, is not universally accepted as routine test in all patients with thyroid nodule(s). The authors of this paper reappraise critically the matter of Ctn measurement in view of the recent advancements in the literature to point out the essential information to be known, and then to prepare an easy-to-use guide for clinicians to appropriately consider the measurement of serum Ctn during clinical practice.

Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer.AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC.MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015–2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice.RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was &gt; 122 pg/ml, from lymph nodes &gt;35.8 pg/ml.CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

Calcitonin Measurement in Needle Washout Fluid After Fine Needle Aspiration As a Complementary Diagnostic Test in Medullary Thyroid Carcinoma

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

An Undetectable Postoperative Calcitonin Level Is Associated with Long-Term Disease-Free Survival in Medullary Thyroid Carcinoma: Results of a Retrospective Cohort Study.

Background: Calcitonin measurement is widely used in the diagnosis, prognosis, and follow-up of patients with medullary thyroid carcinoma (MTC). The prognostic value of undetectable postoperative calcitonin (POCal) in long-term disease outcomes remains uncertain. Objective: The aim of this study is to evaluate POCal as a prognostic marker for long-term MTC disease status. Methods: A retrospective cohort study was carried out. We collected data from the medical records of patients with MTC attending two tertiary teaching hospitals. Patients were divided according to POCal into two groups: undetectable (below the detection limit) or detectable. The outcome was determined at the last medical visit and defined as disease free (undetectable calcitonin and no evidence of disease on imaging), persistent disease (detectable calcitonin with or without structural disease), or disease-related death. Results: Three hundred thirty-four MTC patients were included in the study. The mean age at diagnosis was 41.1 ± 18.6 years; 202 patients (60.5%) were women; and 167 patients (50.0%) had sporadic MTC. The median tumor size was 2.0 cm (1.1-3.5 cm); 164 patients (49.1%) had lymph node metastasis and 63 patients (18.9%) had distant metastasis. At the first postoperative evaluation (3-6 months after surgery), 141 patients had undetectable POCal (mean age = 37.9 years, 70.9% women, median tumor size 1.5 cm [0.7-2.5 cm]; 28 [19.9%] had lymph node metastasis and none had distant metastasis). After a median follow-up of 7.7 years (2.1-13.2 years), 127 (90.1%) of these patients were free of disease, whereas 14 (9.9%) had persistent biochemical disease with stable calcitonin levels. No patient with undetectable POCal died of the disease. In the detectable POCal group (mean age = 42.9 years, 52.8% women, median tumor size 3.0 cm [1.8-4.2 cm]; 136 [70.5%] had lymph node metastasis and 63 [32.6%] had distant metastasis), 18 (9.2%) patients achieved disease-free status, 51 (26.6%) had biochemical disease, and 61 (31.6%) had persistent structural disease. Sixty-three (32.6%) patients died of disease-related events. Further analysis using a multivariate model identified undetectable POCal as an independent prognostic variable for disease-free status (HR = 5.33, CI = 2.86-9.94; p < 0.001). Conclusions: POCal is a strong prognostic marker for long-term disease-free survival and might help define follow-up strategies for MTC patients.

RF07 | PSUN366 An Uncommon Path Leading to Diagnosis of Multiple Endocrine Neoplasia 2A

Abstract Introduction MEN2 is a rare Autosomal Dominant disorder resulting from mutations in the RET proto-oncogene. MEN2 is classified into two distinct syndromes: MEN2A and MEN2B. MEN2A is a syndrome that presents with Medullary Thyroid Carcinoma (MTC) in 90% of adult gene carriers, unilateral or bilateral pheochormocytoma in 50%, and multigland parathyroid tumors in 20-30% of affected individuals. Other rare variants of MEN2 include Familial Medullary Thyroid Carcinoma (FMTC), MEN2A with cutaneous lichen amyloidosis, and MEN2A or FMTC with Hirschprung's disease. We present a patient with incidentally noted elevated calcitonin levels, later diagnosed with MEN2A. Clinical Case 37-year-old Caucasian male was referred to our clinic for elevated calcitonin levels noted on lab work done as part of evaluation and management for weight loss prior to initiating GLP-1 agonists. He was diagnosed with hypothyroidism and multinodular goiter and started on Synthroid. His only symptoms were weight gain, tiredness, soft stools and facial flushing He denied any family history of endocrine disorders. Physical exam was unremarkable. Pertinent labs included serum calcitonin 93 pg/mL (&amp;lt;10 pg/mL), serum CEAg 5.2 ng/mL (0-3 ng/mL), and work up for pheochromocytoma and hyperparathyroidism was negative. USG thyroid showed a left lobe thyroid nodule measuring 7×5×7 mm with macrocalcifications, a right lobe thyroid nodule measuring 8×5×10mm, and an abnormal left lateral level III LN. He underwent left thyroid lobectomy with level VI neck dissection (total thyroidectomy aborted due to hypoxia), and subsequently completion thyroidectomy with right central neck dissection. Pathology showed metastatic MTC with pathologic staging pT1aN1a. Genetic testing showed RET c. 1826G&amp;gt;A (p. C609Y) which is ATA – MOD risk. Patients’ father was also genetically screened and diagnosed with MEN2A and noted to have elevated calcitonin levels. He also subsequently underwent total thyroidectomy, which revealed medullary thyroid microcarcinoma. Conclusion A number of studies support that measurement of serum calcitonin is the most sensitive screening test for detecting occult MTC in individuals with thyroid nodules. Yet, the use of serum calcitonin in the routine evaluation of thyroid nodules is controversial due to absence of uniform calcitonin thresholds, high false positive values and unavailability of pentagastrin stimulation testing. Moreover, there are no recommendations based on the current data to check calcitonin levels prior to initiating GLP-1 agonists but their use is not recommended in patients with personal or family history of MTC/MEN2. Based on the above case, measurement of calcitonin levels should be a part of the work up in patients who present with thyroid nodules and are receiving GLP-1 agonists. Attention should also be paid to the importance of genetic counseling in first-degree relatives of patients with MEN2A. This allows for timely diagnosis and reduces morbidity and mortality. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The trends in early precision diagnosis and treatment strategies of multiple endocrine neoplasia type 2

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism and extra-endocrine features, and two forms subtyped as MEN2A and MEN2B. Based on the correlation between RET proto-oncogene mutation and MEN2 phenotype, MEN2 could be prevented through prenatal diagnosis and preimplantation genetic testing. Integrating the detection of RET mutation with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could accurately predict the progression of MEN2, and then facilitating implementation of personalized precision treatment. In addition, increased awareness of MEN2 is needed, which requires participation of physicians, patients/family members, and relevant organizations, supplemented by psychological support, which could promote the comprehensive management of MEN2. The "5P" strategies for MEN2 represents a paradigm of precision medicine, which could effectively avoid or reduce the clinical adverse outcomes, improve the prognosis and quality of life of MEN2 patients.

ODP466 Case of Sporadic Medullary Thyroid Cancer Detected by Serum Calcitonin Measurement

Abstract Introduction Thyroid nodules are common and their prevalence has increased with more widespread neck sonography. While most thyroid nodules are benign their evaluation and surveillance is centered around identifying nodules that harbor malignant growths. While secular trends suggest progressively increasing prevalence of thyroid cancer, it is largely an indolent generally curable disease. Medullary thyroid cancer (MTC) is comparatively rare (3-5% of all thyroid cancer) and significantly more virulent than the common papillary thyroid cancer. Guidelines regarding screening for potential MTC remain controversial. We describe the case of a patient with sporadic MTC detected by routine serum calcitonin measurement. Clinical case; The patient is a 52 yr old Caucasian man referred after a serendipitous finding of thyroid calcifications found on Neck and Chest CT done for radiculopathy evaluation. He had no neck symptoms and no anomalies on clinical neck examination nor history of radiation exposure nor relevant family neoplastic history. The neck ultrasound showed a multinodular goiter with a dominant hypoechoic 1.4 cm nodule in the right hemi-thyroid with microcalcifications (TIRADS 5). The nodule biopsy showed pauci-cellular specimen with abundant colloid and the patient had opted for repeat serial sonography rather repeat biopsy because of his unpleasant experience with the first biopsy. Routine initial endocrine evaluation included thyroid function tests (normal) and a random serum calcitonin; 267 (n; &amp;lt;15pg/ml). This degree of elevation was confirmed on repeated measures. A calcitonin stimulation test with calcium gluconate showed a peak stimulated calcitonin of 786 pg/ml. Total thyroidectomy and central neck dissection, confirmed a diagnosis of MTC (T1a N1a Mx). Only one of six sampled neck lymph nodes showed metastatic disease. RET mutation testing was -ve and 4 months post surgery his calcitonin is 97pg/ml with no radiologic evidence of any residual or recurrent disease. Discussion The patient's clinical presentation is typical of sporadic MTC (found serendipitously) which while uncommon is more prevalent than familial MTC and has a significantly more virulent clinical course than the much more prevalent classic papillary thyroid cancer. It also has significantly less cure potential and greater morbidity and mortality risk making early detection and aggressive management even more vital. Despite not being included in many guidelines for standard evaluation of thyroid nodules the random calcitonin obtained in the patient was central to the prompt and correct diagnosis of the patient. Conclusions Despite the limitations and caveats to its interpretation, our case highlights the potential utility of routine serum calcitonin measurement as part of the routine screening work up of thyroid nodules even in so called "low risk" clinical presentations with no clinical flags suggestive of possible familial MTC or MEN 2. Presentation: No date and time listed

The dilemma of routine testing for calcitonin thyroid nodule’s patients to detect or exclude medullary carcinoma: one single negative test should be valuable as rule-out strategy to avoid further calcitonin measurements over time

PurposeWhile calcitonin (CT) measurement is recognized as the most accurate tool to diagnose medullary thyroid carcinoma (MTC), its routine use in patients with thyroid nodule (TN) is not universally accepted. The present study raised the question whether a TN patient with an initial normal CT can have suspicious CT levels (i.e., at least >20 pg/ml) later during his follow-up.MethodsThe historical database of our institution was searched to select TN patients undergone multiple CT tests, having an initial normal CT, and clinically followed up for years. The event of a CT above 20 pg/ml (mild-to-moderate suspicion) and 100 pg/ml (high suspicion) was searched in the follow-up of the included patients.ResultsAccording to the study design, the study sample encompassed 170 patients (131 female, 39 male) with initial CT value ≤10 pg/ml. On the first CT test, patients were 54.8 years and median CT was 2.1 pg/ml in both females and males. Over a period of 14.5 years and a median clinical follow-up of patients of 53.0 (23.9–102.5) months, MTC could be excluded by histology or cytology in 109 (64%) and clinically in the remaining ones. On the follow-up over time, no patients had CT >20 pg/ml and only two cases had CT just above 10 pg/ml.ConclusionAccording to the present results, one single CT testing with normal value could be reasonably used as a rule-out strategy in patients with TN to avoid further CT measurements.

Diagnostic Utility of Procalcitonin for Sporadic Medullary Thyroid Carcinoma in Patients with Nodular Disease and Mild or Moderate Hypercalcitoninemia.

Many authors recommend the measurement of serum calcitonin (Ctn) to screen for sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules. In this situation, procalcitonin (pro-Ctn) would have greater utility in patients with hypercalcitoninemia<100 pg/ml. The aim of this study was to evaluate the utility of pro-Ctn in patients with thyroid nodules and without a suspicion of familial MTC or type 2 multiple endocrine neoplasia who had mild or moderate hypercalcitoninemia without an apparent cause. Consecutive patients with nodular thyroid disease assessed routinely by Ctn measurement were selected. Sixty patients with basal Ctn>10 pg/ml but<100 pg/ml were included. Nine patients (15%) had MTC, with cytology being diagnostic in only four. Among the 51 patients without MTC, pro-Ctn was<0.1 ng/ml in 46 (90.2%). All patients with MTC had pro-Ctn>0.1 ng/ml. Basal Ctn was>24.6 pg/ml in all patients with MTC and in 42 patients (82.3%) without MTC. It is noteworthy that among patients with basal Ctn>24.6 pg/ml (n=18) pro-Ctn>0.1 ng/ml identified all patients with MTC and 64.2% of subjects with these pro-Ctn concentrations had this tumor. In conclusion, we did not find superiority of pro-Ctn over Ctn for the diagnosis of sporadic MTC in patients with nodular disease and mild or moderate hypercalcitoninemia. However, in the case of patients with hypercalcitoninemia in the gray zone, pro-Ctn has an excellent negative predictive value while the data regarding its positive predictive value are not uniform.

Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis

PurposeThe sensitivity of cytology after fine needle aspiration (FNA-cytology) in detecting medullary thyroid carcinoma (MTC) is low. To overcome this problem, measuring calcitonin (CT) in washout fluid of FNA (FNA-CT) has been largely diffused and showed good performance. However, no evidence-based study exists comparing systematically the sensitivity of FNA-cytology and FNA-CT. This study aimed to systematically review the literature and collect data allowing a head-to-head comparison meta-analysis between FNA-cytology and FNA-CT in detecting MTC lesions.MethodsThe online databases of PubMed/MEDLINE and Scopus were searched until June 2021. Original articles reporting the use of both FNA-cytology and FNA-CT in the same series of histologically proven MTC lesions were included They were extracted general features of each study, number of MTC lesions (nodule and neck lymph nodes), and true positive and false negatives of both FNA-cytology and FNA-CT.ResultsSix studies were included. The sensitivity of FNA-cytology varied from 20% to 86% with a pooled value of 54% (95% CI 35–73%) and significant heterogeneity. The sensitivity of FNA-CT was higher than 95% in almost all studies with a pooled value of 98% (95% CI 96–100%) without heterogeneity. The sensitivity of FNA-CT was significantly higher than that of FNA-cytology.ConclusionsFNA-CT is significantly more sensitive than FNA-cytology in detecting MTC. Accordingly, FNA-CT represents the standard method to use in patients with suspicious MTC lesions, combined with cytology.