Serum Calcitonin Concentrations Research Articles

A Comparative Study of Calcium Metabolism between Quail and Domestic Rabbits

The existing study was conducted to evaluate calcium; vitamin D and calcitonin concentration in two types of amniotes that live in the Iraqi environment include the local rabbit and the Japanese quail. The study included 18 female Japanese quail Coturnix coturnix, weighing 145.5 ± 34.341 g, they were 16 weeks in ages and 18 female local rabbits, Oryctolagus cuniculus, at the age of one years and 1438.5 ± 284.988 g in weight. The results showed that the mean serum calcium concentration in bird and rabbit were 8.134±0.450 (mg/dl) and 7.267±1.761 (mg/dl) respectively and it was significantly at at 0.066 higher in bird in comparison to rabbit, the mean of vitamin D in bird and rabbit were 24.22± 3.159 (ng/ml) and 28.43±4.632 (ng/ml) respectively and it was significantly higher in rabbit than bird at 0.007 while the mean serum calcitonin concentration in bird and rabbit were 1.354±0.1960 (mg/dl) and 1.676±0.4151 (mg/dl) respectively and it was significantly at 0.009 higher in rabbit in comparison to bird. Egg laying, shell calcification and medullary bone formation induce more extra demand of calcium in birds while the high rate of teeth erupting demand extra calcium in rabbits, the metabolism of vitamin D will be altered indirectly by these process which associated with increased requirements for calcium. The study showed an increase in the level of calcium in both rabbits and quail birds, and that this increase will change the metabolism of vitamin D, and many physiological processes will occur.

In vivo assessment of bone repair by an injectable nanocomposite scaffold for local co-delivery of autologous platelet-rich plasma and calcitonin in a rat model

Background Gellan gum is obtained from the bacterium Sphingomonas elodea and is a polysaccharide with carboxylic acid functional groups. The goal of this project was to investigate the osteoinductive effect of local administration of calcitonin through an injectable scaffold of gellan gum containing salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, and platelets rich plasma. Methods The femur of rats was defected by creating a 2 × 5 mm2 hole using an electric drill. The defect was filled with an injectable hydrogel scaffold composed of gellan gum enriched with salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, platelets rich plasma, and then the radiologic images were taken. Bone densitometry and the histologic studies were carried out by Hematoxylin & Eosin test. Biochemical analysis was done to measure the serum alkaline phosphatase (ALP), calcium, and calcitonin concentration. Results Healing of the bone defects and bone densitometry in the treated group by calcitonin-loaded scaffold was significantly higher (p < 0.05) and bone formation occupied 75% of the defect was greater than in other groups. Serum ALP and calcium levels in the scaffold-loaded calcitonin group were more than in the other groups (p < 0.05). The osteogenic marker genes also increased significantly (p < 0.05) with free calcitonin and the scaffold. Conclusions Gellan gum-based scaffold loaded with calcitonin may be considered a promising local treatment to progress bone formation in repairing skeletal injuries.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma

BackgroundMedullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor. Patients and methodsA retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC. The main parameters were safety and objective treatment response to selpercatinib. ResultsSix children (three males and three females, aged 3–12 years), four with MEN2B and two MEN2A, are reported. All had initial total thyroidectomy and extensive neck dissections but subsequently developed recurrent and progressive disease. All experienced an improvement in clinical symptoms with a concomitant biochemical response evidenced by significant fall in serum calcitonin and CEA concentrations. The fall in serum calcitonin was evident within 2 weeks of the start of selpercatinib, and responses were ongoing at a median follow-up of 13 months (range, 11–22 months). Four children with measurable radiological disease had good volume reduction. The most common adverse effects were transient but reversible grade 1 or 2 increase in alanine aminotransferase, serum bilirubin and constipation. No child required a dose modification or had to discontinue selpercatinib because of a drug-related adverse event. ConclusionSelpercatinib has shown excellent therapeutic efficacy with minimal toxicity in children with MEN2 and progressive metastatic RET-mutated MTC.

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.

Selpercatinib Is a Promising Treatment Option for RET-Mutated Medullary and RET Fusion-Positive Thyroid Cancers

Selpercatinib Is a Promising Treatment Option for <i>RET</i>-Mutated Medullary and <i>RET</i> Fusion-Positive Thyroid Cancers

Changes in Serum Calcitonin Concentrations, Incidence of Medullary Thyroid Carcinoma, and Impact of Routine Calcitonin Concentration Monitoring in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL).

Increases in serum calcitonin, a tumor marker for medullary thyroid carcinoma (MTC), have been associated with glucagon-like peptide 1 receptor agonist use in some preclinical studies. We report calcitonin changes in exenatide-treated and placebo-administered participants and MTC incidence in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and consider the impact of within-trial calcitonin monitoring. EXSCEL participants were randomized 1:1 to once-weekly exenatide 2 mg or placebo. Serum calcitonin was measured at baseline (with trial medication discontinued if >40 ng/L) and annually thereafter (with trial medication discontinued if ≥50 ng/L). Median calcitonin concentrations were calculated at each time point, and thyroid malignancies were collected prospectively. Data regarding follow-up after an elevated calcitonin were collected retrospectively. At baseline, 52 (30 exenatide and 22 placebo) participants had calcitonin >40 ng/L, and during follow-up an additional 23 participants (15 exenatide and 8 placebo) had calcitonin ≥50 ng/L in the intention-to-treat population. Median calcitonin concentrations were similar between treatment groups at baseline with no increase over time. Confirmed MTC occurred in three participants (2 exenatide and 1 placebo), all of whom had significantly elevated baseline calcitonin values (413, 422, and 655 ng/L). During a median 3.2 years' follow-up, no change in serum calcitonin was seen with exenatide therapy. The three confirmed cases of MTC all occurred in participants with markedly elevated baseline calcitonin levels, measured prior to trial medication administration. Regular calcitonin monitoring identified no additional cases of MTC, suggesting no benefit of routine calcitonin monitoring during exenatide treatment.

Changes in serum calcitonin concentrations, incidence of medullary thyroid carcinoma, and impact of routine calcitonin concentration monitoring in the Exenatide study of Cardiovascular Event Lowering (EXSCEL)

Changes in serum calcitonin concentrations, incidence of medullary thyroid carcinoma, and impact of routine calcitonin concentration monitoring in the Exenatide study of Cardiovascular Event Lowering (EXSCEL)

Changes of macrominerals and calcitropic hormones in serum of periparturient dairy cows subject to subclinical hypocalcaemia.

The aims of the study reported in the Research Communication were to evaluate changes of macrominerals and major calcitropic hormone concentrations in 51 healthy dairy cows over the peripartum period, and to compare those cows with 51 cows subject to subclinical hypocalcaemia (SCH) on calving day. The results showed that serum calcium (Ca) and potassium (K) concentrations were lowest in the healthy periparturient dairy cows at parturition, while sodium (Na) and parathyroid hormone (PTH) concentrations were highest. Serum magnesium (Mg), chloride (Cl) and phosphorus (P) concentrations were highest 1 wk prepartum, however, the concentration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was highest 1 wk postpartum. The dairy cows with subclinical hypocalcaemia (SCH) had significantly lower serum levels of Ca, K, Na, Mg, Cl, 1,25(OH)2D3 and glucose and had significantly higher levels of serum P, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) than their healthy counterparts on calving day. However, the serum calcitonin and PTH concentrations were not significantly different between the two groups. These data demonstrated that the concentrations of macrominerals and major calcium regulating hormones of cows change dramatically over the peripartum period. Furthermore, SCH was associated with a risk of the development of ketosis and fatty liver.

Changes in bone turnover and calcium homeostasis during pregnancy and lactation in mammals: a meta-analysis.

Large amounts of calcium are required during pregnancy and lactation to support fetal and neonatal bone growth and calcification. An inadequate supply of calcium during these stages can lead to unsuccessful reproduction or impaired offspring fitness. During reproduction, female mammals undergo numerous physiological changes, including adaptations to allow an adequate supply of calcium. The lack of quantitative studies analysing these physiological changes from a comparative perspective limits our ability to explain and understand these adaptations. Herein, we present our meta-analysis of studies reporting changes in bone turnover and calcium homeostasis during pregnancy and lactation in 14 species of mammals. Our meta-analysis of 60 studies showed that all species have a similar pattern of physiological changes during pregnancy and lactation, which include: (1) decreased serum calcium concentrations; (2) bone tissue loss; (3) decreased serum calcitonin and parathyroid hormone concentrations; and (4) increased serum calcitriol concentration, regardless of changes in parathyroid hormone concentrations. In addition, we found a negative relationship between: (1) serum calcium concentrations and the number of teats; and (2) serum parathyroid hormone concentrations and litter mass.

Prognostic value of preoperative serum calcitonin concentration on primary surgery outcomes in medullary thyroid cancer

Prognostic value of preoperative serum calcitonin concentration on primary surgery outcomes in medullary thyroid cancer

Association of plasma calcium concentrations with alcohol craving: New data on potential pathways

Recently, calcium was suggested to be the active moiety of acamprosate. We examined plasma calcium concentrations in association with severity of alcohol dependence and its interaction with regulating pathways and alcohol craving in alcohol-dependent patients. 47 inpatient alcohol-dependent patients undergoing detoxification treatment underwent laboratory testing, including calcium, sodium, liver enzymes as well as serum concentrations of calcitonin, parathyroid hormone and vitamin D. The psychometric dimension of craving was analyzed with the Obsessive Compulsive Drinking Scale (OCDS). The severity of withdrawal was measured with the Alcohol Dependence Scale (ADS) and with the Alcohol Dependence Scale for high-risk sample (ADS-HR). The main findings of our investigation are: a) a negative correlation of plasma calcium concentrations with alcohol craving in different dimensions of the OCDS; b) a negative correlation of plasma calcium concentrations with breath alcohol concentration; c) lowered calcitonin concentration in the high-risk sample of alcoholics; d) lowered plasma vitamin D concentrations in all alcoholic subjects. Our study adds further support for lowered plasma calcium concentrations in patients with high alcohol intake and especially in patients with increased craving as a risk factor for relapse. Lowered calcitonin concentrations in the high-risk sample and lowered vitamin D concentrations may mediate these effects. Calcium supplementation could be a useful intervention for decreasing craving and relapse in alcohol-dependent subjects.

Effects of Dulaglutide on Thyroid C Cells and Serum Calcitonin in Male Monkeys.

Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type 2 diabetes, have caused hyperplasia/neoplasia of thyroid C cells in rodent carcinogenicity studies. Studies in monkeys have not identified an effect of GLP-1 receptor agonists on thyroid C cells; however, group sizes were small. Dulaglutide is a once-weekly, long-acting human GLP-1 receptor agonist recently approved in the United States and the European Union. The objective of this study was to determine whether dulaglutide altered C-cell mass in monkeys. Male cynomolgus monkeys (20 per group) were sc injected with dulaglutide 8.15 mg/kg (∼500-fold maximum human plasma exposure) or a vehicle control twice weekly for 52 weeks. Basal and calcium gluconate-stimulated serum calcitonin concentrations were obtained at 3, 6, 9, and 12 months. Thyroid glands were weighed, fixed, and sectioned at 500-μm intervals. C-cell volumes were measured using an automated image analysis. C-cell proliferation was estimated using Ki67/calcitonin colabeling and cell counting. Administration of dulaglutide 8.15 mg/kg twice weekly for 52 weeks did not increase serum calcitonin in monkeys or affect thyroid weight, histology, C-cell proliferation, or absolute/relative C-cell volume. This study represents a comprehensive evaluation of the monkey thyroid C cells after dosing with a GLP-1 receptor agonist, with a large group size, and measurement of multiple relevant parameters. The lack of effect of dulaglutide on C cells is consistent with other studies in monkeys using GLP-1 receptor agonists and suggests that nonhuman primates are less sensitive than rodents to the induction of proliferative changes in thyroid C cells by GLP-1 receptor agonists.

Reference range of serum calcitonin in pediatric population.

Children belonging to the multiple endocrine neoplasia type 2 (MEN 2) pedigree and carrying germline RET mutations are candidates for prophylactic thyroidectomy, the timing of which is based on the mutation-associated risk and the calcitonin (CT) levels. The aim of this study was to establish the reference range for serum CT in a pediatric population. The study included 2740 subjects (1339 females and 1401 males) ranging in age from 1 day to 16 years and undergoing blood testing for any medical condition not affecting serum CT. Overall, serum CT was undetectable in 61.5% of the samples and detectable in 38.5%. Detectable samples were more frequent in the first 2 years of life. Thereafter, undetectable samples became more frequent, particularly in females. Mean serum CT concentrations were higher in the first year of life (9.81 ± 8.8 pg/mL; range, 2.0-48.9 pg/mL) and the second year of life (4.56 ± 2.64 pg/mL; range, 2.0-14.7 pg/mL). A significant decrease of serum CT levels was observed thereafter (P < .001), and starting from the third year of life serum CT levels were similar to those found in adults. No gender difference was found in any age group. Based on these results, age-specific CT reference ranges are needed in the pediatric population, and especially in the first 2 years of life. This is the first study defining the reference range for serum CT in the pediatric population and large enough to be statistically meaningful. Our proposal may facilitate the process of decision making when dealing with gene carriers of MEN 2.

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.

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.

Smoldering medullary thyroid carcinoma liver metastasis 37 years after resection of an organ‐confined tumor

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that usually behaves aggressively. After resection, serological surveillance for calcitonin and carcinoembryonic antigen (CEA) is used to prompt a radiographic search for metastatic disease. We report a case of a 65-year-old woman who presented with a large liver metastasis 37 years after she underwent thyroidectomy for organ-confined MTC. Her clinical course over that time showed a smoldering pattern in which she was symptom free until presentation even though her serum calcitonin and CEA concentrations were elevated for 17 years, and a small equivocal radiographic lesion in the liver was detected 10 years prior to presentation. Cytopathology from an ultrasound guided fine needle aspiration of the hepatic lesion was diagnostic for metastatic MTC. This case highlights the ability for smoldering residual MTC to suddenly transform to aggressive biological behavior after a long period of clinical remission.

Timing and criteria for prophylactic thyroidectomy in asymptomatic RET carriers – the role of Ct serum level

Authors summarize in this brief review results of European discussion, held on ETA-CRN Meeting in Lisbon, 2009, on the American Thyroid Association Medullary Thyroid Cancer (MTC) Guidelines published in the same year and focus on the timing of prophylactic thyroidectomy. ATA 2009 guidelines classified RET protooncogene mutation carriers into 4 levels: A, B, C, D. ATA for prophylactic thyroidectomy were generally independent of the serum calcitonin (Ct) concentration but based on a priori risk levels. This was well accepted as the important novelty was to delineate risk level specially for RET 634 mutation (level C). In the ATA Guidelines total prophylactic thyroidectomy below age 5 years was recommended in RET 634 mutation carriers regardless of Ct status. However, some European experts favored to base the decision not only on the results of DNA testing but also on the going Ct level. The European discussion reflected divergent opinions and indicated the need of publication of European experience instead of arbitrary opinions. It was stressed that patients carrying the same RET mutation present heterogenic progression to the clinically overt medullary thyroid cancer, even in the same family. Thus, in summary, the ATA MTC guidelines constituted a positive stimulus to publish further evidence for Ct-guided pre-emptive thyroidectomy for RET gene mutation carriers and the conclusion is drawn on the basis of experience expressed in Lisbon and published later evidence that the integrated algorithm based on age - Ct - type of RET mutation should be considered in the decision of pre-emptive thyroidectomy.

The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5mg kg(-1) b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06mg kg(-1) b.w. estradiol dipropionate (EDP) once a day for 3weeks. A peroxidase-antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an imagej public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis.

The Vitamin D Receptor in Thyroid Development and Function

Background and Objective: Vitamin D is known to modulate thyroid neoplastic and autoimmune disease. We investigated the role of the vitamin D receptor (VDR) in normal thyroid development and function (thyrocytes and C cells). Methods: The thyroid phenotype of VDR knockout mice was studied in comparison to wild-type controls. The mice were fed a normal diet or a calcium-rich diet to circumvent effects induced by hypocalcemia. Results: Thyroid morphology was unaltered in VDR knockout mice. Also, expression of different parameters of thyrocyte function was comparable (immunohistochemistry). C cell physiology was, however, affected in the absence of the VDR, resulting in increased thyroidal calcitonin expression (immunohistochemistry), paralleled by increased serum calcitonin levels, but only in normocalcemic mice. To study a possible effect of vitamin D status on basal calcitonin levels in humans, serum calcitonin concentrations were compared between vitamin D-deficient and -sufficient patients (serum 25-OH vitamin D₃ ≤10 and ≥40 ng/ml, respectively), but no difference was observed. Conclusions: In mice, the VDR is redundant for normal thyrocyte function, but not for C cell function, where it mediates the negative control of calcitonin by 1,25-dihydroxyvitamin D₃. In patients, vitamin D status does not affect basal serum calcitonin levels. A study in healthy individuals is needed to confirm these findings.

Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.