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Objective: To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study., Methods: Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups., Results: Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01)., Conclusion: This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rosenblum, Hirsch, Grozinsky-Glasberg, Benbassat, Yoel, Ishay, Zolotov, Bachar, Banne, Levy and Twito.)

Background: Cytological limitations pose a challenge to preoperative diagnosis of medullary thyroid carcinoma (MTC) and therefore, a significant subset of patients is only diagnosed postoperatively. The objective of this study was to investigate the impact of knowledge of a preoperative MTC diagnosis on disease management and outcomes. Methods: Multicenter, retrospective, cohort study of MTC patients treated in Israel from January 2000 to June 2021. We compared cohorts of patients according to the presence or absence of a preoperative MTC diagnosis. Results: Ninety-four patients with histologically confirmed MTC were included (mean age 56.2 ± 14.3 years, 43% males). Fifty-three patients (56%) had a preoperative MTC diagnosis (preop-Dx group), and 41 (44%) were confirmed only postoperatively (no-Dx group). The extent of surgical resection, including completion procedures, was as follows: total thyroidectomy in 83% versus 100% ( p  = 0.002), central lymph node dissection (LND) in 46% versus 98% ( p  < 0.001), ipsilateral lateral LND in 36% versus 79% ( p  < 0.001), and contralateral lateral LND in 17% versus 28% (NS), in the no-Dx versus the preop-Dx group, respectively. Pathology confirmed a smaller median tumor size of 16 ± 17.4 mm versus 23 ± 14.0 mm ( p  = 0.09), a higher proportion of micro-MTC (size ≤10 mm) 32% versus 15% ( p  = 0.03), and a higher rate of co-occurrence of follicular cell-derived carcinoma 24% versus 4% ( p  = 0.003), in the no-Dx compared to the preop-Dx group, respectively. The rates of extrathyroidal and extranodal tumor extension were not significantly different between the groups. At the last follow-up, the biochemical cure was attained in 55% [CI 0.38-0.71] compared to 64% [CI 0.50-0.77] of the no-Dx and the preop-Dx group, respectively ( p  = 0.41). After the exclusion of patients with micro-MTC, biochemical cure was more commonly achieved in the preop-Dx group (33% [CI 0.14-0.52] vs. 62% [CI 0.46-0.77], p  = 0.04). Preop-Dx patients had improved overall survival compared to the no-Dx group (log-rank p  = 0.04) over a median follow-up of 82 months (interquartile range [IQR] 30-153). Conclusions: Preoperatively, the diagnosis of MTC is often missed. An accurate preoperative diagnosis of MTC may enable guideline-concordant surgical treatment and ultimately contribute to an overall survival benefit in MTC patients.

Context: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors., Objective: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) positron emission tomography (PET)/computed tomography (CT) in patients with metastatic MTC and to determine their eligibility for peptide receptor radionuclide therapy (PRRT)., Methods: We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at 5 centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS)., Results: Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95% CI 8-25) and a median OS of 63 months (95% CI 21-not reached). Of the entire cohort, the median OS was 323 months (95% CI 152-not reached). Predictors of poorer OS included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity, and age ≥60 years., Conclusions: The prevalence of high tumor avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC., Materials and Methods: A retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated., Results: Study population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005)., Conclusions: This study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Multiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC patients followed for long period are scarce. This study evaluated the association between baseline clinico-pathologic variables and response to initial treatment and short- and long-term disease outcomes in sporadic and familial MTC., Methods: Patients treated for MTC at four tertiary medical centers were retrospectively analyzed. Clinical and pathological data were collected. The outcomes measured included disease persistence 1 year after diagnosis, disease persistence at last follow-up, disease-related mortality (DRM) and all-cause mortality., Results: The study enrolled 193 patients (mean age: 48.9 ± 18.7, 44.7% males), of whom 18.1% were familial cases. The mean follow-up period was 10.1 ± 9.4 years (8.5 ± 8.1 in sporadic and 16.9 ± 11.6 in familial MTC). Disease persistence 1-year after diagnosis and at last follow-up was detected in 56.1 and 60.4% patients, respectively. All-cause and DRM were 28.5 and 12.6%, respectively. Extra-thyroidal extension (ETE) and distant metastases (DM) were associated with disease persistence at last follow-up. ETE and DM were also significantly associated with DRM. Complete remission 1 year after diagnosis had high correlation with no evidence of disease at last follow-up (Cramer's V measure of association 0.884, P < 0.001) and with 100% disease-specific survival (Cramer's V measure of association 0.38, P < 0.001)., Conclusions: Apart from clinico-pathologic parameters, close correlation was found between 1-year status and long-term prognosis. These results underscore the importance of combining classical and dynamic factors for both sporadic and familial MTC prognostication and treatment decision making.

Background: The widespread use of neck sonography in recent years has led to a dramatic increase in the detection of thyroid cancer, accompanied by changes in the clinicopathologic features of the disease. However, small papillary carcinomas account for the bulk of this increase, while little is known about temporal changes in medullary thyroid carcinoma (MTC). The aim of this study was to evaluate trends in the presentation, treatment, and outcome of MTC., Methods: Patients treated for MTC at four medical centers in Israel were divided into three groups by year of diagnosis: 19811995 (period A), 1996-2005 (period B), and 2006-2016 (period C). Clinicopathologic and survival data were collected retrospectively from the medical files and compared between the groups., Results: The cohort included 182 patients (54.9% female) with a mean age of 49.2 ± 18.7 years: 43 (23.6%) diagnosed in period A, 54 (29.7%) in period B, and 85 (46.7%) in period C. No significant differences were found between the groups in primary tumor size (25.7 ± 18.9 mm, 26.6 ± 18 mm, and 23.7 ± 17.6 mm, respectively), proportion of micro-MTC (30.8%, 20.0%, and 25.3%, respectively), or TNM staging. Age at diagnosis significantly increased over time (38.7 ± 17.2 years, 51.7 ± 18.4 years, and 53.7 ± 17.7 years, respectively; p < 0.001), and the rate of familial MTC significantly decreased (41.9%, 14.8%, and 8.2%, respectively; p = 0.002). Although the implementation of cervical lymph node dissection increased (62.1%, 78.4%, and 85%, respectively; p = 0.01), detection of metastatic lymph nodes decreased from 88.9% in period A to 65.0% in periods B and C (p = 0.06). There was no difference between the groups in disease-specific survival or disease-free state at one year from diagnosis (37.5%, 43.1%, and 50%, respectively) and last follow-up (27%, 41.2%, and 48%, respectively). Similar findings on MTC presentation and outcomes were obtained when only patients with non-familial MTC were analyzed., Conclusions: Unlike differentiated thyroid cancer, most of the presenting features of MTC have not changed over time. The most significant temporal change is a decreased rate of familial MTC. Despite more extensive surgery and the use of new treatment modalities in recent years, significant improvement in disease-related outcomes were not found.

Background: Liver metastases are relatively common in patients with metastatic medullary thyroid carcinoma (MTC), carrying a negative impact on disease prognosis. The options for selective therapy of liver metastases in MTC patients are limited to catheter-guided procedures such as trans-arterial chemoembolization (TACE). Data regarding the effectiveness and safety of this procedure in MTC are limited., Aim: To explore the clinical outcome, survival and safety profile of TACE for liver metastases in a group of MTC patients., Methods: Retrospective case series of patients treated at a single tertiary University Medical Center from 2005 to 2015., Results: Seven consecutive patients (mean age 64.5 ± 10.9 years, 5 females) with histologically confirmed MTC with liver metastases were included. Metastatic involvement of the liver was less than 50% of the liver volume in all patients. The median size of the largest liver lesion was 40 ± 6.9 mm. The patients underwent in total 20 sessions of TACE. Clinical improvement as well as tumor response (PR) were observed in all patients. The median time to tumor progression was 38 months (range 8-126). Three patients were still alive at the end of the follow-up period (a median overall survival rate of 57 ± 44 months)., Conclusion: TACE in MTC patients with hepatic metastases is usually well tolerated and induces both clinical improvement and tumor response for prolonged periods of time in the majority of patients. This therapeutic option should always be considered, irrespective of the presence of extrahepatic metastasis., (© 2017 European Society of Endocrinology.)

Background: No increased mortality has been reported in patients with thyroid papillary microcarcinoma (PMC); however, neck recurrences and distant metastases have been described. In this study, we compare patients' outcomes after total thyroidectomy vs hemithyroidectomy for treatment of thyroid PMC., Methods: Two hundred and ninety-three patients from two major medical centers in Israel were included. The mean follow-up period was 7.2±6.8 yr., Results: Total thyroidectomy was performed in 214 patients and hemithyroidectomy in 79 patients. Mean tumor size was 6.3±3 mm. Lymph-node (LN) metastases and extraglandular extension were more frequent in the total thyroidectomy group than in the hemithyroidectomy group, 24.8% vs 1.3% (p<0.001) and 11.7% vs 3.8% (p=0.042), respectively. The cumulative incidence of recurrence at the end of follow-up was 13.2% in the total thyroidectomy group and 14.3% in the hemithyroidectomy group (p=ns). The incidence of recurrence was higher in patients with LN involvement in both groups. Considering low risk patients only (monofocal tumors, no LN involvement, no extraglandular extension; no.=63 in the total thyroidectomy group vs no.=60 in the hemithyroidectomy group) neck recurrence was found in 10% of patients in the hemithyroidectomy group but none in the total thyroidectomy group. In the hemithyroidectomy group, all locoregional recurrences were diagnosed using ultrasonography, compared to 47.6% in the total thyroidectomy group., Conclusion: For patients with monofocal disease within the thyroid gland and no LN involvement, hemithyroidectomy can be considered an option, bearing in mind a higher risk for recurrence. For all other patients with PMC, we propose total thyroidectomy as initial treatment.

Background: Thyroglobulin is an excellent biological marker of persistent or recurrent thyroid cancer during long-term follow-up. Most studies investigated its diagnostic value but not its prognostic value over time. We aim to study the prognostic value of thyroglobulin levels early after total thyroidectomy, before iodine ablation., Methods: The study was based on the Rabin Medical Center registry of patients with non-medullary thyroid carcinoma. Data were collected on the clinical, laboratory, and outcome characteristics of 420 consecutive patients followed at our institution for whom early post-operative pre-ablation thyroglobulin values (baseline thyroglobulin) were available., Results: Patients were classified into 4 groups by baseline thyroglobulin level: 0-2, 2-10, 10-100, and >100 ng/ml. Higher levels were associated with a shift toward male gender (p=0.01), larger tumor size (p=0.02), and a more extensive disease (p<0.0001). They were also related to disease persistence and evidence of disease at last follow-up (p<0.0001). The 10 ng/ml cut-off level identified patients with persistent disease with a sensitivity and specificity of 73%, positive predictive value of 43%, and negative predictive value of 89%. On multivariate analysis, the following variables were predictive of persistent disease: baseline thyroglobulin level, male gender, lymph-node involvement, distant metastases, higher tumor invasiveness, and larger tumor size. However, the predictive power of baseline thyroglobulin level was relatively weak (odds ratio 1.002, 95% confidence interval 1.00-1.04)., Conclusions: In patients with well-differentiated thyroid cancer, a post-thyroidectomy thyroglobulin level <10 ng/ml is associated with a low probability of having persistent disease and can be used combined with other disease characteristics for decisions regarding treatment and follow-up.

Background: Familial nonmedullary thyroid cancer (FNMTC) is a disease defined by clustering of thyroid cancers of follicular cell origin, and it is estimated to account for 5% of all thyroid cancers. Several studies found FNMTC to be more aggressive than sporadic disease, whereas others found them to have a similar course and outcome. The purpose of this study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer., Methods: A retrospective controlled study of FNMTC versus sporadic nonmedullary thyroid cancers was conducted using a registry of patients with thyroid cancer. Data on disease severity at presentation, treatment modalities, and outcome were collected., Results: Sixty-seven patients with FNMTC and 375 controls with sporadic disease were included. Follow-up period was 8.6 ± 10 years for patients with FNMTC and 8.4 ± 9.1 years for sporadic cases. Patients with FNMTC had comparable disease severity at diagnosis as sporadic patients, underwent similar surgical and radioiodine treatments, and had similar long-term disease-free survival. Long-term outcome in families with three or more affected relatives was similar to families with only two affected relatives., Conclusions: Our results suggest that FNMTC is not more aggressive than sporadic thyroid cancer within our studied population. After a similar therapeutic strategy, FNMTC and sporadic cases had comparable prognosis, including in families with three or more affected members.

Background: Papillary thyroid cancer (PTC) commonly affects women of child-bearing age. During normal pregnancy, several factors may have a stimulatory effect on normal and nodular thyroid growth. The aim of the study was to determine whether pregnancy in thyroid-cancer survivors poses a risk of progression or recurrence of the disease., Methods: The files of 63 consecutive women who were followed at the Endocrine Institute for PTC in 1992-2009 and had given birth at least once after receiving treatment were reviewed for clinical, biochemical, and imaging data. Thyroglobulin levels and neck ultrasound findings were compared before and after pregnancy. Demographic and disease-related characteristics and levels of thyroid-stimulating hormone (TSH) during pregnancy were correlated with disease persistence before conception and disease progression during pregnancy using Pearson's analysis., Results: Mean time to the first delivery after completion of thyroid-cancer treatment was 5.08 ± 4.39 years; mean duration of follow up after the first delivery was 4.84 ± 3.80 years. Twenty-three women had more than one pregnancy, for a total of 90 births. Six women had evidence of thyroid cancer progression during the first pregnancy; one of them also showed disease progression during a second pregnancy. Another two patients had evidence of disease progression only during their second pregnancy. Mean TSH level during pregnancy was 2.65 ± 4.14 mIU/L. There was no correlation of disease progression during pregnancy with pathological staging, interval from diagnosis to pregnancy, TSH level during pregnancy, or thyroglobulin level before conception. There was a positive correlation of cancer progression with persistence of thyroid cancer before pregnancy and before total I-131 dose was administered., Conclusions: Pregnancy does not cause thyroid cancer recurrence in PTC survivors who have no structural or biochemical evidence of disease persistence at the time of conception. However, in the presence of such evidence, disease progression may occur during pregnancy, yet not necessarily as a consequence of pregnancy. The finding that a nonsuppressed TSH level during pregnancy does not stimulate disease progression suggests that it may be an acceptable therapeutic goal in this setting.

Over-expression of the proto-oncogene Akt/PKB has been demonstrated in some neuroendocrine tumor models. Akt may activate downstream proteins such as mTOR and p70S6K, inducing tumor proliferation. The rapamycin-derivative RAD001, everolimus, interacts with this pathway by antagonizing mTOR, but its effects on neuroendocrine tumors are largely unknown. We explored the mechanism of action of RAD001 on cell proliferation, hormonal secretion and on Akt/mTOR/p70S6K pathway activation, in a human medullary thyroid carcinoma (MTC) cell-line (TT) and in cells derived from human MTCs. Treatment with RAD001 significantly inhibited cell viability in a dose- and time-dependent fashion, and diminished phosphorylation of Akt downstream targets, mTOR and p70S6K, in both TT cell-line and cultured human MTCs. Akt phosphorylation was not affected by RAD001. RAD001 induced cell-cycle arrest in the G(0)/G(1) phase in TT cells, but had no effect on apoptosis. Moreover, RAD001 did not affect calcitonin and carcinoembryonic antigen secretion in TT cells and in human MTCs. RAD001 seems to have potent anti-proliferative effect in human MTC cells, which suggest that clinical trials of this agent are of considerable interest., (2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with differentiated thyroid cancer (DTC) usually have a good prognosis but may experience a decline in quality of life (QOL). The way patients perceive their illness may have a major impact on their QOL. Our hypothesis was that patients with DTC frequently perceive their illness as much more severe than its objective clinical characteristics indicate. The aim of the study was to investigate how patients with DTC perceive their illness and to correlate these findings to various demographic parameters as well as objective indices of disease severity., Methods: The self-administered Illness Perception Questionnaire-Revised (IPQ-R) was completed by consecutive patients with DTC during routine follow-up at the endocrine clinic. The questionnaire consists of three parts that measure different aspects of illness perception. The patients' medical records were reviewed for data on demographic parameters (sex, age) and indices of disease severity (duration of DTC, disease stage at diagnosis, number of operations, number of radioactive iodine treatments, and evidence of disease persistence/recurrence). The patients were also asked for additional data on family status, level of education, and employment status. Pearson and Spearman correlations and analysis of variance were used for statistical analysis., Results: The study group included 110 patients (91 women) of mean age 53.5 years. Level of education was the only demographic factor found to affect the patients' perception of their illness. There was no correlation of patient illness perception and cancer stage. Among the disease-severity parameters, time since last treatment, evidence of disease persistence, and number of iodine treatments were significantly associated with a negative disease perception. Number of iodine treatments was the most broadly affecting factor. There was a high correlation of scores among the various illness perception subscales., Conclusions: Patients with DTC perceive their illness on a subjective, emotional basis unrelated to its actual severity. To improve patients' illness representations and, consequently, their QOL, a trained psychologist should be included in the multidisciplinary team that manages patients with DTC. Attention should be particularly directed to less-educated patients and patients who require repeated iodine treatments.

Background: The rapid increase in the incidence of well-differentiated thyroid cancer in recent years is the result of smaller thyroid tumors (1 cm or less) being diagnosed more frequently. Few studies are available regarding the appropriate approach to this previously known postmortem incidental finding, and their results remain controversial., Methods: In 2005, our center started a registry of all patients with nonmedullary thyroid carcinoma who were followed at our institute. In the present study, data on the background, clinical, and outcome characteristics were collected from the registry for 225 patients with microscopic disease and 543 patients with macroscopic disease., Results: Patients with microscopic disease were slightly older (51 vs. 47.5 years, p = 0.003), had a higher female to male ratio (189:37 vs. 419:123; p = 0.06), and were affected more by papillary carcinoma (98.2% vs. 85.5%; p < 0.001). Multifocal disease was documented in 50.2% of the patients with microscopic disease and 46.8% of the patients with macroscopic disease (NS), and bilateral disease, in 42.6% and 36.8%, respectively (NS). Corresponding rates for the two groups for other tumor-related factors were as follows: lymph node involvement at initial treatment, 25.7% and 30% (NS); distant metastases, 2.4% and 5.1% (p = 0.16); persistent/recurrent disease, 11% and 32% (p < 0.001); and new distant metastases, 2.65% and 6.5% (p = 0.07). At a median follow-up of 5 years, 96% of the microscopic carcinoma group were disease free compared to 77% of the macroscopic group (p < 0.001)., Conclusion: The differences between patients with microscopic and macroscopic well-differentiated thyroid carcinoma may not justify a different therapeutic approach.

Objective: To identify prognostic factors of clinical outcome and long-term survival in medullary thyroid cancer (MTC)., Design: Retrospective case series of 51 consecutive patients (mean age 46.9 years, 57% female) treated at a single tertiary university medical center from 1970 to 2005. Medical records were reviewed for demographic data, laboratory and clinical course, treatment, and long-term outcome., Main Outcome: At presentation, 25 patients (49%) had local disease and 26 (51%) had metastatic disease (three with distant metastases). RET mutations were identified in nine of 23 patients tested. The patients with hereditary disease were younger than the patients with sporadic disease (p < 0.001) and had lower calcitonin levels at diagnosis (p = 0.004) and more multicentric tumors (p = 0.02). Initial surgery consisted of total thyroidectomy in 47 patients, with neck dissection in 26; 22 patients achieved long-term remission. The 5-, 10- and 15-year survival rates were 88%, 85%, and 77%, respectively. On univariate analysis, distant metastases during the course of the disease and elevated calcitonin levels postoperatively were significant prognostic factors of reduced survival (p = 0.001 and 0.016, respectively). Lymph node involvement at initial surgery was associated with a lower remission rate (p = 0.016) but had no impact on long-term survival (p = 0.269)., Conclusion: Patients with MTC have a generally favorable outcome, perhaps owing to recent advances in diagnosis and treatment. Although postoperative serum calcitonin level and distant metastases are the only determinants of long-term survival, the presence of cervical metastases is predictive of a higher risk of recurrent or persistent disease.