Treating intra-thyroid parathyroid adenoma by radiofrequency is a valuable alternative to hemithyroidectomy.

BACKGROUND: Parathyroid adenoma (PA) is the most common cause of primary hyperparathyroidism (PHPT). One infrequent scenario (0.7%-6%) is represented by intra-thyroid PA (I-PA), an ectopic variant of the parathyroid gland included in the thyroid parenchyma. Radiofrequency (RF) of I-PA seems to be an excellent alternative to hemithyroidectomy for these patients. The present study aimed to report three cases of PHPT and I-PA treated with RF at two institutions. MATERIALS AND METHODS: These two institutions share guidelines for thyroid RF. At both institutions, cases with surgical indication and difficult PA localization are discussed during thyroid multidisciplinary meetings involving all disciplines involved in managing these cases. RF was performed using a Viva RF System generator (STARMED). Ultrasound contrast evaluation was performed using a SonoVue (Bracco). All patients were followed-up by an expert endocrinologist. RESULTS: Three cases had indications for treating I-PA. All patients were proposed to undergo RF rather than hemithyroidectomy, and accepted this option. RF of I-PA was performed with a power of 30-50 W and delivering a total between 0.02 and 0.69 Kcal. The active treatment lasted just more than 1 min. Post-treatment follow-up revealed PTH and calcium normalization. CONCLUSION: This study showed highly encouraging results in favor of treating I-PA with RF.

Preoperative neck ultrasound combined with pathological data can significantly impact the outcome of medullary thyroid carcinoma.

The diagnosis of medullary thyroid carcinoma (MTC) is challenging since the accuracy of ultrasound (US) and fine-needle aspiration cytology are suboptimal. As a result, MTC has a generally poor prognosis. The aim of this study was to analyze whether perioperative data can modify the risk of relapse in these patients. The institutional database of Turin Mauriziano Hospital was searched to extract records of MTCs diagnosed between 2000 and 2021. Kaplan-Meier curves and Cox and logistic regression analyses were performed, and the hazard ratio (HR) was calculated. Seventy-three MTC patients (median age 58 yr) were found. Disease-free survival was significantly different according to staging (HR: 9.12; p = 0.037), capsular status (HR: 5.49; p = 0.02), and neck US (HR: 9.19; p = 0.04). In the logistic regression analysis, CEA level (ß: -0.01; p = 0.043), histological multifocality (OR: 7.4; p = 0.034), and metastatic lymph nodes at histology (ß: -0.13; p = 0.006) were significantly associated with structural recurrence. Two logistic multivariate models best explained the variance in recurrence: 1) neck US presentation plus histological multifocality (AIC: 27; r2: 0.37; x2: 12.4; p = 0.002) and 2) number of neck metastases plus capsular invasion (AIC: 26; r2: 0.40; x2: 13.7; p = 0.001). Pathological data are associated with MTC prognosis. Preoperative neck US can significantly help to predict MTC outcome.

Suboptimal accuracy of ultrasound and ultrasound-based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta-analysis.

OBJECTIVE: Ultrasound (US) is the pivotal procedure during the diagnostic work-up of thyroid nodule and several US-based risk stratification systems (RSSs) have been recently developed. Since the performance of RSSs in detecting medullary thyroid carcinoma (MTC) has been rarely investigated, the present systematic review aimed to achieve high evidence about (1) how MTC is classified according to RSSs; (2) if RSSs correctly classify MTC at high risk/suspicion, and (3) if MTC is classified as suspicious at US when RSSs are not used. DESIGN: The review was performed according to MOOSE. The online search was performed by specific algorithm on January 2022. A random-effects model was used for statistical analysis. RESULTS: Twenty-five papers were initially included and their risk of bias was generally low. According to ATA system, 65% of MTCs was assessed at high suspicion and 25% at intermediate suspicion. Considering all RSSs, a 54.8% of MTCs was put in a high-risk/suspicion category. Pooling data from studies without data of RSS the prevalence of ultrasonographically suspicious MTCs was 60%. CONCLUSIONS: As conclusion, MTC presentation according to RSSs is partially known and it is classified in a high-risk/suspicion category of RSSs in just over a half of cases. This advises for further studies, ideally supported by international societies, to better define the US presentation of MTC.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Determining an energy threshold for optimal volume reduction of benign thyroid nodules treated by radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) is effective in reducing the volume of benign thyroid nodules. However, what parameters can influence the response to RFA is still unclear. The present study aimed to (1) investigate which ultrasound and technical parameters are potential determinants of the volumetric reduction; (2) develop a dose-response model, and (3) analyze the effects of RFA on ultrasound features. METHODS: In this retrospective study, three institutions treated patients with benign thyroid nodules according to the same protocol. The technical parameters were power and energy. The 1-year volume reduction ratio (VRR) was the reference standard of the response. The correlations of different parameters with VRR were analyzed and the association between several parameters and a VRR above 50% studied by uni- and multivariate analyses. The probit regression estimated the probability to achieve an effective response. RESULTS: One hundred fifteen patients were enrolled. The median power was 50 W and median total delivered energy 27,531 J. At 1-year follow-up, the median VRR was 64.0% and 87 (75.7%) nodules showed a VRR above 50%. Among all parameters, only baseline volume, total energy, and energy per volume were independently associated to a VRR > 50% (p = 0.001, p = 0.0178, p < 0.001 respectively). The probit regression analysis demonstrated that delivering 756 J/ml and 2670 J/ml gave a probability of VRR > 50% in 50% and 99% of patients, respectively. CONCLUSIONS: Considering the baseline nodular volume and delivering the adequate energy per volume allow optimizing technical and clinical success. KEY POINTS: • The effectiveness of radiofrequency ablation in treating benign thyroid nodules is negatively correlated to the volume of the nodule and positively correlated to the energy delivered per volume. • When planning the treatment, the total energy to deliver can be calculated by using a simple formula: nodular volume × 2670 J.

Graves' orbitopathy: a multidisciplinary approach.

Orbitopathy is the main extra thyroidal manifestation of Graves' disease. It is a very challenging condition, which requires a cooperation between many specialists (endocrinologists, ophthalmologists, radiologists, radiotherapeutic, orbital surgeons) for an optimal clinical management. An accurate diagnostic assessment is required, in order to plan an adequate treatment of Graves' orbitopathy. Medical therapy, radiotherapy or surgery may be necessary to control the disease. In this review, the authors analyze the various therapeutic strategies, as well the more recent therapies based on pharmacologic immunomodulation.

Is concomitant treatment with steroids and radiotherapy more favorable than sequential treatment in moderate-to-severe graves orbitopathy?

PURPOSE: Glucocorticoids (GCs) and external radiotherapy (RT) are used for treating moderate-to-severe Graves' orbitopathy (GO). We aimed to assess whether GCs and RT were more effective when administered concomitantly or sequentially. METHODS: We retrospectively analyzed clinical outcomes [assessed by Clinical Activity Score (CAS) and NOSPECS classification] in 73 patients treated with both i.v. GCs and RT. The patients were divided in two groups: In group A (53 patients), RT was delivered concomitantly with GCs, and in group B (20 patients) RT was administered subsequently to the end of methylprednisolone. RESULTS: At baseline, CAS (median 4.0) and the percentage of patients encompassing the various grades of the classes 2, 3 and 4 of the NOSPECS score were similar in both groups. Six months after RT, CAS decreased to 2 in both groups (p = 0.0003 vs baseline) as well as NOSPECS class 4 (p < 0.0001 vs baseline). NOSPECS class 2 improved more in group A than in group B (p = 0.016). The median cumulative dose of GCs was lower in group A than in group B (median 4.500 vs 6000 mg, p < 0.007); the overall length of therapy was shorter in group A than in group B (68 vs 106 days, p < 0,02). The most common acute adverse effect was transient conjunctivitis (five in group A and three in group B); seven patients (five in group A and two in group B, age between 60 and 66 years) developed cataract, requiring surgery in five cases. CONCLUSIONS: Concomitant administration of GC and RT showed a favorable effect in moderate-to-severe GO, thus suggesting that RT should be carried out early during steroid therapy, when clinical symptoms do not improve or deteriorate after the first i.v. administrations of GCs.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Could Transplantation into the Thyroid Gland Benefit Pancreatic Islet Grafting in Unstable Type 1 Diabetes (T1DM), Complicated Type 2 Diabetes (T2DM), and Patients with Total Pancreatectomy?

BACKGROUND: Insular allograft for unstable type 1 diabetes and autograft in pancreatectomy patients are nowadays considered established procedures with precise indications and predictable outcomes. The clinical outcome of islet transplantation is similar to that of pancreas transplantation, avoiding the complications associated with organ transplantation. OBJECTIVE: We hypothesised that transplantation of islets of Langerhans within an endocrine organ could better promote their engraftment and function. This could help to resolve or ameliorate known pathological conditions such as unstable type 1 diabetes and complicated type 2 diabetes. RATIONALE: Pancreatic islet transplantation is currently performed almost exclusively in the liver. The liver provides a sufficiently favourable environment, although not entirely. The hepatic parenchyma has a lower oxygen tension than the pancreatic parenchyma and the vascular structure of the liver is not typical of an exclusively endocrine organ. Moreover, islet transplantation into the liver is not without complications, including hematoma or portal vein thrombosis. PROPOSED PROJECT: The thyroid gland is the endocrine gland proposed as a 'container'. In fact, it has all the characteristics of 'physio-compatibility' which can address the objectives assumed. It is indeed an ideal site because it is an easily accessible anatomical site that allows islets to be implanted using ultrasound-guided transcutaneous inoculation technique. Moreover, it has physiological and anatomical endocrine affinities with pancreatic islets and, if necessary, it can be removed, using hormone supplementation or replacement therapy. CONCLUSIONS: The thyroid gland may be proposed as an ideal site for islet implantation due to its anatomical and physiocompatibility characteristics.

Radiofrequency ablation is an effective treatment for Bethesda III thyroid nodules without genetic alterations.

Background: Radiofrequency ablation (RFA) is effective in the treatment of thyroid nodules, leading to a 50-90% reduction with respect to baseline. Current guidelines indicate the need for a benign cytology prior to RFA, though, on the other side, this procedure is also successfully used for the treatment of papillary microcarcinomas. No specific indications are available for nodules with an indeterminate cytology (Bethesda III/IV). Aim: To evaluate the efficacy of RFA in Bethesda III nodules without genetic alterations as verified by means of a custom panel. Methods: We have treated 33 patients (mean delivered energy 1069 ± 1201 J/mL of basal volume) with Bethesda III cytology, EU-TIRADS 3-4, and negative genetic panel. The mean basal nodular volume was 17.3 ± 10.7 mL. Results: Considering the whole series, the mean volume reduction rate (VRR) was 36.8 ± 16.5% at 1 month, 59.9 ± 15.5% at 6 months, and 62 ± 15.7% at 1-year follow-up. The sub-analysis done in patients with 1 and 2 years follow-up data available (n = 20 and n = 5, respectively) confirmed a progressive nodular volume decrease. At all-time points, the rate of reduction was statistically significant (P < 0.0001), without significant correlation between the VRR and the basal volume. Neither cytological changes nor complications were observed after the procedure. Conclusion: RFA is effective in Bethesda III, oncogene-negative nodules, with reduction rates similar to those obtained in confirmed benign lesions. This procedure represents a good alternative to surgery or active surveillance in this particular class of nodules, regardless of their initial volume. A longer follow-up will allow to evaluate further reduction or possible regrowth.

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.

Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

Continuous subcutaneous rhPTH infusion for managing difficult chronic hypoparathyroidism. A systematic review.

PURPOSE: Standard treatment for chronic hypoparathyroidism is represented by long-life per os supplementation of calcium and vitamin D. Since 90s, exogenous PTH is also available, but a not negligible number of patients experience a poor control. Starting from the experience with pumps in diabetes, it has been hypothesized that the infusion of PTH through pump might result in a better disease control. The aim of this systematic review is to summarize the published data about continuous subcutaneous PTH infusion in chronic hypoPTH patients and achieve conclusions for clinical practice. METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted by two authors independently (last search on November 30, 2022). All findings were summarized and critically discussed. RESULTS: We included 14 of the 103 retrieved articles, 2 RCTs, 8 case reports, and 4 case series, published between 2008 and 2022. Of the total 40 patients, 17 were adults, and 23 pediatric. The etiology was postsurgical in 50% of cases and genetic in the other 50%. All had a failure of standard care and a rapid improvement of clinical and biochemical parameters on PTH pump therapy, without severe adverse events. CONCLUSIONS: Based on literature, pump PTH infusion may represent an effective, safe, and feasible option for patients with chronic hypoparathyroidism refractory to standard therapy. From a clinical perspective, careful patient selection, a skilled healthcare team, the assessment of the local setting and the collaboration with pump suppliers are essential.

A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study.

CONTEXT: The risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features. OBJECTIVE: To develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors. METHODS: In a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction. RESULTS: By ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis. CONCLUSION: Current risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

A Prospective Multicenter Study Examining the Relationship Between Thyroid Cancer Treatment Outcomes and the Presence of Autoimmune Thyroiditis.

Background: There is some controversy on the potential relationship between autoimmune processes and clinicopathologic features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis (AT) and 1-year thyroid cancer treatment outcomes in a large multicenter study using prospectively collected data. Methods: We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (no autoimmune thyroiditis [noAT]) of associated AT. We used propensity score matching to compare the clinical features and outcomes between the two groups at 1-year follow-up. Results: We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had AT. Before propensity score matching, AT patients were significantly younger and had a smaller and bilateral tumor (p < 0.0001). Patients with AT more frequently fell into the low- and intermediate-risk categories, while the ATA high risk was more frequent among noAT patients (p = 0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared with patients without AT (7.3% vs. 4.5%, p = 0.001), with an odds ratio of 1.86 ([confidence interval: 1.3-2.6], p = 0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% vs. 2.7%, p = 0.35). The elevated risk associated with the ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions: In this large prospective series, biochemical persistence was more frequent, at 1-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.

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.

PURPOSE: The 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. METHODS: The 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. RESULTS: Six 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. CONCLUSIONS: FNA-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.

Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application.

Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign thyroid nodules from malignant ones. About 20% of FNAC yields indeterminate results leading to unnecessary or delayed surgery. Many studies of tissue samples, the majority of which are retrospective advocate testing for RET rearrangements as a diagnostic adjunctive tool in thyroid nodules with indeterminate cytological findings. Because of the uncertain prevalence of RET rearrangements, its utility as a tumor marker is still controversial. The goal of this study was to establish the prevalence and the utility of testing for RET rearrangements in FNAC suspicious of cancer in a clinical setting. In this prospective study, we analysed a large series of thyroid aspirates by RT-PCR only and Southern blot on RT-PCR products for type 1 and 3 RET rearrangements. Results were compared with clinical findings, cytological diagnosis and final histopathology. By the higher sensitive Southern-blot on RT-PCR method, RET rearrangements were present in 36% of papillary thyroid carcinomas (RET/PTC-1, 12%; RET/PTC-3, 20%; both, 4%) and of 13.3% of benign nodules. By means of RT-PCR only, RET rearrangements were disclosed only in 14.3% of PTC and in 3.6% of benign nodules. No significant correlation was found between RET rearrangements and clinicopathological features of patients. These results indicate that molecular testing of thyroid nodules for RET/PTC must take into account of its high prevalence in benign nodules, inducing false positive diagnoses when the highly sensitive assay Southern-blot on RT-PCR is used. Its searching by means of RT-PCR only, has a specificity superior of conventional cytology and can be used to refine inconclusive FNAC.