Combining TSH measurement with TIRADS assessment to further improve the detection of thyroid cancers.

BACKGROUND: Thyroid Imaging Reporting and Data Systems (TIRADSs) have demonstrated high performance in risk stratification of thyroid nodules (TNs). However, further improvements are needed in view of the ongoing project of an international TIRADS. Even if thyroid-stimulating hormone (TSH) measurement is traditionally used to assess the thyroid function, several papers have reported that higher TSH levels are associated with the presence of differentiated thyroid carcinoma (DTC). The present study aimed to investigate the role of TSH levels as improvement factor of American College of Radiology (ACR-), European Thyroid Association (EU-), and Korean Society (K-)TIRADS. METHODS: Patients undergoing thyroidectomy were reviewed and TNs were re-assessed according to TIRADSs. Different TSH subgroups were attained. Histology was the reference standard. DTC risk of relapse was assessed according to American Thyroid Association guidelines. RESULTS: The study series included 97 patients with 39.2% cancer prevalence. ACR-, EU-, and K-TIRADS indicated fine-needle aspiration cytology (FNAC) in 78.9%, 81.6%, and 92.1% of cases, respectively. All high-risk DTC had FNAC indication according to the three TIRADSs. The cancer rate was significantly lower in patients with TSH<0.4 mIU/L (P=0.04). The receiver operating characteristic (ROC) curve analysis showed that the best TSH cut-off to detect DTC patient was >1.3 mIU/L with Area Under the Curve (AUC)=0.70. Combining TSH data with TIRADS, the sensitivity of ACR-, EU-, and K-TIRADS increased to 92.1% 89.5%, and 94.7%, respectively. Conversely, the rate of unnecessary FNAC raised. At multivariate analysis, gender, TSH, and TIRADS were independent predictors of cancer. CONCLUSIONS: Even if TIRADSs are strongly reliable to stratify the risk of malignancy of TNs, measuring TSH can further improve our sensitivity in detecting DTC.

Performance of ACR-TIRADS in assessing thyroid nodules does not vary according to patient age.

AIMS: A few studies have evaluated the performance of the American College of Radiology Thyroid Imaging Reporting And Data System (ACR-TIRADS) in pediatric and elderly patients and found differences between the latter two age groups and middle adulthood. Thus, the present study was undertaken to explore the possible variation of ACR-TIRADS performance across different ages of patients. METHODS: A retrospective population undergoing thyroidectomy was selected to use histology as the reference standard. Ultrasound images were reviewed, and alignment of ACR-TIRADS with the corresponding histological diagnosis was made afterwards. Results of the age groups were compared. The ACR-TIRADS diagnostic performance was calculated considering the assessment of nodules across risk categories (i.e., from TR1 to TR5), rate of unnecessary FNAC (UN-FNAC), and rate of necessary but non-performed FNAC (NNP-FNAC). RESULTS: Overall, 114 patients with a total of 220 nodules (46 carcinomas) were included. The rate of UN-FNAC was 66.3%, being 93.1% in TR3, 82.1% in TR4, and 31.4% in TR5. There were 15 NNP-FNACs. No significant difference was observed between age groups in terms of sample size, nodule, cancer, and FNAC. The nodule assessment according to ACR-TIRADS categories did not vary across ages. Sensitivity and specificity recorded in three age tertiles were not significantly different. CONCLUSIONS: The present study shows that the performance of ACR-TIRADS is not significantly influenced by patient age.

Prevalence and Management of Complications of Percutaneous Ethanol Injection for Cystic Thyroid Nodules: A Systematic Review of Literature and Meta-analysis.

BACKGROUND: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. METHODS: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with 95% confidence intervals (CI). I2 statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. RESULTS: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1-2%], I2 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results.The pooled prevalence rate of local pain was 21% (CI [16-27] I2 90.3). Local pain was typically transient and mild, sometimes moderate and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1-2], I2 0). Dysphonia was transient and could last from several some hours to twelve months after PEI. CONCLUSIONS: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique.

Risk of TIRADS-based inappropriate FNAC in autonomous thyroid nodules is clinically negligible.

Objective: Thyroid nodule (TN) is usually managed according to Thyroid Imaging And Reporting Data Systems (TIRADS) with the major aim to reduce as much as possible unnecessary fine-needle aspiration cytologies (UN-FNACs). Since the assessment of autonomously functioning thyroid nodule (AFTN) according to TIRADS is heterogeneous, that virtually benign entity may increase the rate of UN-FNAC. This study retrospectively analyzed the appropriateness of TIRADS-based FNAC indication in AFTNs, also looking at the impact of TSH and nodule size. Methods: Cases diagnosed with AFTN on scintigraphy were searched. Patients who had undergone AFTN treatment, were on medications or supplementation that could affect thyroid function, or had multiple AFTNs were excluded. The AFTNs were assessed according to ACR-TIRADS. Results: Forty-eight AFTNs were included of which 37.5% had FNAC indication according to TIRADS. The FNAC indication rate in the case of TSH lower than 0.4 mIU/L was significantly higher than in other cases (P = 0.0078). The most accurate TSH cut-off and AFTN size associated with UN-FNAC were ≤ 0.41 mIU/L and > 22 mm, respectively. The multivariate analysis showed that both TSH and nodule size were independent predictors of UN-FNAC with OR of 6.65 and 6.46, respectively. According to these data, the rate of FNAC indication dropped to 4.16%. Conclusion: Inappropriate FNACs in AFTNs are primarily observed in patients with low TSH and large AFTN. Since these cases typically undergo scintigraphy, the risk of TIRADS-based UN-FNAC is clinically negligible. There is no need for integrating other imaging procedures into the TIRADS model.

The value of ACR, European, Korean, and ATA ultrasound risk stratification systems combined with RAS mutations for detecting thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules.

PURPOSE: The aim of this study was to evaluate the diagnostic value of four commonly utilized ultrasound (US) RSSs, namely, the American College of Radiology [ACR], European [EU], Korean [K] TI-RADSs and American Thyroid Association [ATA] US-based RSS criteria, in combination with activating point mutations of the RAS genes (NRAS, HRAS, and KRAS) for detection of thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules. METHODS: We retrospectively analyzed cytologically indeterminate and suspicious for malignancy thyroid nodules which underwent US, molecular testing and surgery between September 1, 2018, and December 31, 2023. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC, 95% confidence interval [CI]) was calculated. RESULTS: A total of 100 cytologically indeterminate and 24 suspicious for malignancy thyroid nodules were analyzed. Compared to the four US-based RSSs alone, the diagnostic value of the four US-based RSSs combined with RAS mutations did not significantly improved (cytologically indeterminate, AUC [95% CI] 0.6 [0.5-0.7] and 0.6 [0.5-0.7], respectively, p = 0.70; cytologically suspicious for malignancy, AUC [95% CI] 0.7 [0.5-0.9] and 0.8 [0.6-0.9], respectively, p = 0.23). CONCLUSIONS: The diagnostic value of the four main US-based RSSs (ACR, EU, K, and ATA) was not improved in conjunction with the evaluation of RAS mutations for preoperative risk stratification of cytologically indeterminate thyroid nodules. CLINICAL RELEVANCE STATEMENT: In cytologically indeterminate nodules categorized according to US-based RSSs, isolated RAS positivity does not reliably distinguish between benignity and malignancy.

Continuous Glucose Monitoring and Recreational Scuba Diving in Type 1 Diabetes: Head-to-Head Comparison Between Free Style Libre 3 and Dexcom G7 Performance.

Background: Scuba diving was previously excluded because of hypoglycemic risks for patients with type 1 diabetes mellitus(T1DM). Specific eligibility criteria and a safety protocol have been defined, whereas continuous glucose monitoring (CGM) systems have enhanced diabetes management. This study aims to assess the feasibility and accuracy of CGM Dexcom G7 and Free Style Libre 3 in a setting of repetitive scuba diving in T1DM, exploring the possibility of nonadjunctive use. Material and Methods: The study was conducted during an event of Diabete Sommerso® association in 2023. Participants followed a safety protocol, with capillary glucose as reference standard (Beurer GL50Evo). Sensors' accuracy was evaluated through median and mean absolute relative difference (MeARD, MARD) and surveillance error grid (SEG). Data distribution and correlation were estimated by Spearman test and Bland-Altman plots. The ability of sensors to identify hypoglycemia was assessed by contingency tables. Results: Data from 202 dives of 13 patients were collected. The overall MARD was 31% (Dexcom G7) and 14.2% (Free Style Libre 3) and MeARD was 19.7% and 11.6%, respectively. Free Style Libre 3 exhibited better accuracy in normoglycemic and hyperglycemic ranges. SEG analysis showed 82.1% (Dexcom G7) and 97.4% (Free Style Libre 3) data on no-risk zone. Free Style Libre 3 better performed on hypoglycemia identification (diagnostic odds ratio of 254.10 vs. 58.95). Neither of the sensors reached the MARD for nonadjunctive use. Conclusions: The study reveals Free Style Libre 3 superior accuracy compared with Dexcom G7 in a setting of repetitive scuba diving in T1DM, except for hypoglycemic range. Both sensors fail to achieve accuracy for nonadjunctive use. Capillary tests remain crucial for safe dive planning, and sensor data should be interpreted cautiously. We suggest exploring additional factors potentially influencing sensor performance.

Primary resistance to selpercatinib in a patient with advanced medullary thyroid cancer.

Selpercatinib, a selective RET kinase inhibitor, has demonstrated remarkable efficacy in treating patients with advanced medullary (MTC) and differentiated thyroid cancer with RET alterations. Primary resistance to selpercatinib is a very uncommon situation, and its underlying mechanisms are poorly understood. We report the case of a 42-year-old female with advanced MTC harboring a somatic M918T RET mutation who exhibited a primary resistance to selpercatinib. Despite prompt treatment initiation after the diagnosis of progressive disease, the patient continued experiencing rapid spread of disease, characterized by the appearance of new metastatic lesions and increased tumor burden. Genomic analysis revealed no additional mutations associated with on-target or off-target resistance. This case highlights a rare clinical scenario of primary resistance to selpercatinib in advanced MTC. While secondary resistance mechanisms have been well-documented, primary resistance remains poorly understood. Possible explanations include tumor heterogeneity and activation of alternative signaling pathways that stills need to be elucidated. Emerging therapies targeting resistance mechanisms and next-generation RET inhibitors offer promising avenues for further investigation.

Meaning of ACR-TIRADS recommendation in favor of follow-up rather than FNAC in thyroid nodules.

Thyroid Imaging Reporting and Data Systems (TIRADSs) have been largely diffused for their high accuracy in risk stratification of thyroid nodules (TNs) and their selection for fine-needle aspiration cytology (FNAC). The most popular TIRADSs are ACR-, EU-, and K-TIRADS, with some discrepancies each other. One major difference is that ACR-TIRADS includes a recommendation in favor of follow-up in TNs having a major diameter insufficient to indicate FNAC. The present study aimed to explore prevalence and significance of this recommendation. EU- and K-TIRADS were used as comparator. A retrospective series of thyroidectomies was searched according to a pre-defined protocol. The study period was 2019-2023. Preoperative ultrasound images were reviewed by radiologists blinded of clinical data. Matching of TIRADS and histology was performed later. Histology was the gold standard. The study series included 39 TNs classified as category 3, 4, or 5 and assessed for follow-up according to ACR-TIRADS. The overall cancer frequency was 25.6%, being 13% in category 3, 20% in category 4, and 83.3% in category 5. The category assessment according to ACR-, EU-, and K-TIRADS was not significantly different. EU-TIRADS indicated FNAC in 10 TNs of which two cancers and eight benign lesions. K-TIRADS recommended FNAC in 32 TNs of which seven cancers and 25 benign lesions. TNs assessed for follow-up according to ACR-TIRADS are cancer in one-fourth of cases. EU- and, especially, K-TIRADS allow us to select for FNAC cancers, with the burden of non-negligible frequency of unnecessary FNACs.

NIFTP-adjusted risk estimation of Bethesda thyroid cytology categories should consider the indication for FNA according to TIRADS.

BACKGROUND: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was firstly described in 2016. Since NIFTP is thought a non-malignant tumor, the Bethesda system for thyroid cytology proposes two estimations of risk of malignancy of the diagnostic categories, one considering NIFTP as cancer and another one considering it as a benign neoplasm. The present study aimed to review NIFTPs in a single center, re-assess them across categories of three Thyroid Imaging Reporting and Data Systems (TIRADSs), and define the indication for biopsy according to the category-specific size cut-offs. METHODS: The study period was from 2017 to 2023. The institutional database was searched for histologically proven NIFTPs with preoperative ultrasound images. NIFTPs were re-assessed according to the American College of Radiology (ACR), European (EU), and Korean (K) TIRADSs. The indication for biopsy was defined according to TIRADS category-specific size threshold. RESULTS: Twenty NIFTPs from 19 patients were included. The median size of the NIFTPs was 23 mm. According to ultrasound, 80-85% of NIFTPs were at low-intermediate risk and 5-15% at high risk without significant difference among the tree TIRADSs (p = 0.91). The indication for FNA, according to three TIRADSs, was found in 52-58% of cases with no significant difference among systems (p = 0.96). CONCLUSION: NIFTPs have heterogeneous presentation according to TIRADSs with very low indication rate for FNA.

Reappraising the role of thyroid scintigraphy in the era of TIRADS: A clinically-oriented viewpoint.

Thyroid nodules (TNs) are a common entity, with the majority being benign. Therefore, employing an accurate rule-out strategy in clinical practice is essential. In the thyroid field, the current era is significantly marked by the worldwide diffusion of ultrasound (US)-based malignancy risk stratification systems of TN, usually reported as Thyroid Imaging Reporting And Data System (TIRADS). With the advent of US (and later TIRADS), the role of thyroid scintigraphy (TS) in clinical practice has gradually diminished. The authors of the present paper believe that the role of TS should be reappraised, also considering its essential role in detecting autonomously functioning thyroid nodules and its limited contribution to detecting thyroid cancers. Thus, this document aims to furnish endocrinologists, radiologists, surgeons, and nuclear medicine physicians with practical information to appropriately use TS.

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study.

The incidence of papillary thyroid carcinoma (PTC) is increasing and PTC ≤ 10 mm (PTMC) accounts for most new diagnoses. PTMCs are not always low risk, as detection of lymph nodes metastasis (LNM) may occur. The purpose of the study was to analyze the clinical pattern, frequency, and independent risk factors of patients with PTMC and LNM. From January 2022 to June 2023, PTCs managed at CTO Hospital, Rome; Policlinico Vanvitelli, Naples; and Garibaldi Nesima Hospital, Catania were included. PTC management followed the same diagnostic-therapeutic procedures according to the ATA guidelines. Variables such as age, sex, maximum diameter, histologic evidence of LNM (HELNM +), Hashimoto's thyroiditis (HT), multifocality, capsule invasion, and histological subtype were considered. PTCs were divided according to HELNM and size. Two hundred ninety-eight PTCs were included. PTMCs were 136 (45.6%) and LNM occurred in 27.2% of them. In the HELNM + group, analysis of PTMC vs 'MacroPTC' (PTC > 10 mm) did not show any statistical difference. Multivariate regression revealed that young age (OR 0.93; CI 95% 0.90-0.96; p < 0.01) and male sex (male OR 3.44; CI 95% 1.16-10.20; p = 0.03) were the only independent risk factors for HELNM + in PTMC. The risk of LNM in PTMC is not negligible; therefore, a careful evaluation by an expert thyroidologist is mandatory for patients with small thyroid nodule, especially in younger and male patients before excluding surgery. In the future, new tools are needed to detect early PTMC with LNM before surgery.

Analysis of dose-TSH response effect of levothyroxine soft-gel formulation.

Background: Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Methods: Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Results: Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 µg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) µg/kg/day, 75% with a dose of 1.38 µg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Conclusions: Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted.

Head-to-head comparison of American, European, and Asian TIRADSs in thyroid nodule assessment: systematic review and meta-analysis.

Context: Ultrasound-based risk stratification systems (Thyroid Imaging Reporting and Data Systems (TIRADSs)) of thyroid nodules (TNs) have been implemented in clinical practice worldwide based on their high performance. However, it remains unexplored whether different TIRADSs perform uniformly across a range of TNs in routine practice. This issue is highly relevant today, given the ongoing international effort to establish a unified TIRADS (i.e. I-TIRADS), supported by the leading societies specializing in TNs. The study aimed to conduct a direct comparison among ACR-, EU-, and K-TIRADS in the distribution of TNs: (1) across the TIRADS categories, and (2) based on their estimated cancer risk. Methods: A search was conducted on PubMed and Embase until June 2023. Original studies that sequentially assessed TNs using TIRADSs, regardless of FNAC indication, were selected. General study characteristics and data on the distribution of TNs across TIRADSs were extracted. Results: Seven studies, reporting a total of 41,332 TNs, were included in the analysis. The prevalence of ACR-TIRADS 1-2 was significantly higher than that of EU-TIRADS 2 and K-TIRADS 2, with no significant difference observed among intermediate- and high-risk categories of TIRADSs. According to malignancy risk estimation, K-TIRADS often classified TNs as having more severe risk, ACR-TIRADS as having moderate risk, and EU-TIRADS classified TNs as having lower risk. Conclusion: ACR-, EU-, and K-TIRADS assess TNs similarly across their categories, with slight differences in low-risk classifications. Despite this, focusing on cancer risk estimation, the three TIRADSs assess TNs differently. These findings should be considered as a prerequisite for developing the I-TIRADS.

Incidence of subclinical and overt hypothyroidism in children treated with [131I]mIBG: a systematic review and meta-analysis.

INTRODUCTION: Treatment with [131I]mIBG is commonly used in pediatric metastatic neuroblastoma (NB); however, unbound [131I]I might be taken up by the thyroid, causing hypothyroidism. To prevent this occurrence, thyroid blockade with iodine salts is commonly used; despite this precaution, thyroid dysfunction still occurs. This review and meta-analysis aim to clarify the mean frequency of hypothyroidism in children with NB treated with [131I]mIBG and to investigate the possible causes. EVIDENCE ACQUISITION: The literature was searched for English-language scientific manuscripts describing the incidence of TSH elevation and overt hypothyroidism in children with NB treated with [131I]mIBG. Preclinical studies, small-case series, and reviews were excluded. A proportion meta-analysis was conducted to test the influence of potentially relevant factors (type and duration of thyroid blockade, year of the study, sample size) on the incidence of TSH elevation/overt hypothyroidism. EVIDENCE SYNTHESIS: Eleven studies were included. The pooled percentage of TSH elevation was 0.41 (95% CI: 0.27-0.55); the duration of the thyroid blockade (P=0.004) was inversely correlated with the incidence of TSH elevation. Moreover, a TSH increase was more common in patients treated with potassium iodide (KI) alone than in those managed with a multi-drug thyroid blockade (P<0.001). The pooled percentage of children requiring hormone replacement therapy was 0.33 (95% CI: 0.16-0.49). As in the case of TSH elevation, a longer duration of the thyroid blockade (P=0.006) and a multi-pronged approach (P<0.001) were associated with a lower incidence of overt hypothyroidism. CONCLUSIONS: Hypothyroidism appears to occur frequently in children treated with [131I]mIBG, which should be monitored closely after the radionuclide treatment to start hormone replacement therapy as soon as needed. The duration, as well as the type of thyroid blockade, seem to influence the incidence of hypothyroidism; however, more data from prospective evaluations are needed.

Thyroid metastasis from renal cell carcinoma presenting as a solid mass with rapid enlargement.

Summary: Thyroid metastases from nonthyroidal malignancies (NTMs) represent a diagnostic challenge, often displaying heterogeneous clinical manifestations. These metastases are rare but significant, accounting for approximately 2% of thyroid malignancies. Distinguishing them from primary thyroid malignancies is challenging due to the lack of specific ultrasound features, and the ultrasound-based risk stratification systems offer limited utility in such cases. Fine needle aspiration cytology is crucial for definitive diagnosis, yet it may not always provide accurate results. In this case report, we describe a unique instance of thyroid metastases originating from renal cell carcinoma, emphasizing the complexities in diagnosis and the importance of considering oncological conditions when assessing thyroid masses. Awareness of thyroid metastasis from NTMs, particularly in cases of diffuse thyroid hypoechogenicity and hypothyroidism, is essential for clinicians in their diagnostic approach. Learning points: Thyroid metastases from nonthyroidal malignancies are diagnostic challenges due to their heterogeneous clinical presentations, often mimicking primary thyroid malignancies. Thyroid metastases from nonthyroidal malignancies are relatively rare, but they still account for approximately 2% of thyroid malignancies. It is fundamental to consider oncological conditions when assessing thyroid masses, especially in cases of diffuse thyroid hypoechogenicity, hypothyroidism, and history of other tumors. Thyroid presentation is quite similar to that of autoimmune hypothyroidism, endocrinologists must be aware of the possibility of thyroid hypofunction due to the massive invasion of the parenchyma.

The American Thyroid Association risk classification of papillary thyroid cancer according to presurgery cytology.

OBJECTIVE: To compare the American Thyroid Association (ATA) risk staging of histologically proven papillary thyroid cancer (PTC) in patients who received a presurgery cytologic result of either indeterminate thyroid nodules (ITNs, Bethesda III/IV) or suspicious for malignancy/malignant (TIR 4/5, Bethesda V/VI). METHODS: Clinical, ultrasonographic, cytological data from patients with histologically diagnosed PTC were retrospectively collected. RESULTS: Patients were stratified according to the preoperative fine-needle aspiration cytology into 2 groups: 51 ITNs (TIR3A/3B) and 118 suspicious/malignant (TIR 4/5). Male/female ratio, age, and presurgery TSH level were similar between the 2 groups. At ultrasound, TIR 4/5 nodules were significantly more frequently hypoechoic (P = .037), with irregular margins (P = .041), and with microcalcifications (P = .020) and were more frequently classified as high-risk according to the European Thyroid Imaging and Reporting Data System (EU-TIRADS; P = .021). At histology, the follicular PTC subtype was significantly more prevalent among ITNs while classical PTC subtype was more frequent in TIR 4/5 group (P = .002). In TIR 4/5 group, a higher rate of focal vascular invasion (P < .001) and neck lymph node metastasis (P = .028) was observed. Intermediate-risk category according to ATA was significantly more frequent in TIR 4/5 group while low-risk category was more frequently found among ITNs (P = .021), with a higher number of patients receiving radioiodine in TIR 4/5 group (P = .002). At multivariate logistic regression, having a TIR 4/5 cytology was associated with a significant risk of having a higher ATA risk classification as compared to ITN (OR 4.6 [95% CI 1.523-14.007], P = .007), independently from presurgery findings (nodule size at ultrasound, sex, age, and EU-TIRADS score). CONCLUSIONS: Papillary thyroid cancers recorded among ITNs are likely less aggressive and are generally assessed as at lower risk according to ATA classification.

Determinants of circulating calcitonin value: analysis of thyroid features, demographic data, anthropometric characteristics, comorbidities, medications, and smoking habits in a population with histological full exclusion of medullary thyroid carcinoma.

Objective: Calcitonin (Ctn) measurement is crucial for the early diagnosis of medullary thyroid carcinoma (MTC). However, Ctn levels can be skewed/elevated due to other reasons, and the Ctn upper reference value remains controversial. In this field, studies have heterogeneous settings, published data are controversial, and no evidence has been achieved. The study's aim was to evaluate all previously investigated Ctn determinants in a population with histological exclusion of MTC. Methods: The institutional records from 2010 to 2022 were reviewed to select patients with thyroid nodules who had undergone total thyroidectomy with histological exclusion of MTC and who had tested for Ctn just before surgery. Thyroid features, demographic and anthropometric data, comorbidities, medications, and lifestyle information were collected. Univariate and multivariate analyses were performed. Results: A total of 127 cases were included. The median age for thyroidectomy was 51 years. Median Ctn was 1.04 pg/mL (interquartile range (IQR) 1.04-2.77), with two cases having values above 10 pg/mL. In univariate analysis, Ctn was correlated with gender (p < 0.001), body weight (p = 0.016), height (p = 0.031), body surface area (p = 0.016), thyroid size (p = 0.03), thyroglobulin (p < 0.001), and chronic kidney disease (p < 0.001). After multivariate analysis, the model with the highest accuracy included gender, chronic kidney disease, and thyroid-stimulating hormone (TSH) with an adjusted R-squared of 0.4. Conclusions: This study demonstrates, in a population histologically proven as MTC-free, that the Ctn value is mainly influenced by gender, anthropometric/thyroid features, and chronic kidney disease, with the further impact of TSH.