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 and a 37.5% of cases had FNAC indication according to TIRADS. The FNAC indication rate of patients with TSH lower than 0.4 mIU/L was significantly higher than the remaining ones (p = 0.0078). The most accurate cut-off of TSH and AFTN size associated with UN-FNAC was ≤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 6.65 and 6.46, respectively. According to these data, the rate of FNAC indication dropped up 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.

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.

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.

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.

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.

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.

Inflammatory Profile Assessment in a Highly Selected Athyreotic Population Undergoing Controlled and Standardized Hypothyroidism.

Background: Hypothyroidism (hT) presents heterogeneous symptoms and findings. Evidence on this topic comes mainly from heterogeneous populations in terms of disease duration, residual thyroid function, and comorbidities. Therefore, it would be useful to assess systemic inflammation in a homogeneous hT population. The aim of this study was to investigate inflammation in a population that underwent standardized controlled hT. Methods: We recruited thyroidectomized patients diagnosed with thyroid cancer who were otherwise fit and healthy, showing hypothyroidism before I131 treatment using a standard protocol of LT4 withdrawal. The blood inflammatory indexes (BIIXs) (i.e., NLR, PLR, MLR, SII, SIRI, and AISI) were calculated using the blood tests collected just before I131 administration. Patients were divided according to sex, BMI, and thyroglobulin. The relationships between the BIIXs, age, and thyroid hormones were also investigated. Results: We included 143 patients. The median age of the sample was 43 years. The BIIX median values showed significant differences based on sex, BMI, and thyroglobulin levels (p < 0.05). No significant correlations were found between the BIIXs and age, TSH, FT4, and FT3. Conclusions: This study shows the BIIX median values of a population which underwent standardized hT. It suggests a role for some BIIXs in the evaluation of hypothyroidism in obese people and as hypothetical prognostic markers for thyroid cancer.

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.

Menstrual Cycle, Glucose Control and Insulin Sensitivity in Type 1 Diabetes: A Systematic Review.

The correlation between the menstrual cycle and glucose control in type 1 diabetes has been the focus of several studies since the 1920s, but a few critical aspects made it particularly challenging to reach conclusive evidence. The aim of this systematic review is to reveal more solid information about the impact of the menstrual cycle on glycaemic outcomes and insulin sensitivity in type 1 diabetes and highlight the less researched areas. The literature was searched by two authors independently using PubMed/MEDLINE, Embase and Scopus (last search on 2 November 2022). The retrieved data did not allow us to perform a meta-analysis. We included 14 studies published between 1990 and 2022, with sample sizes from 4 to 124 patients. We found a wide heterogeneity in the definition of the menstrual cycle phases, glucose metrics, techniques for determining insulin sensitivity, hormonal assessment and other interfering factors considered, with an overall high risk of bias. There is no conclusive evidence, and published data do not allow us to achieve quantitative results. In a subset of patients, a possible worsening of insulin sensitivity and hyperglycaemia in the luteal phase could be observed. From the clinical standpoint, a cautious strategy based on patient-specific patterns can be considered until new, solid evidence is obtained.

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army.

AIM: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. PATIENTS & METHODS: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. RESULTS: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. CONCLUSION: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

Coping strategies in people with type 1 diabetes on insulin pump treatment.

BACKGROUND: In stressed people with diabetes (PWD) glycemia varies idiosyncratically. Coping is a relatively stable personality trait that assesses how individual deals with stress. Insulin pumps are considered the best insulin delivery system but require more attention from PWD, virtually increasing stress levels. Aim of our study was to evaluate the coping strategies adopted by a pool of participants with type 1 diabetes mellitus (T1DM) on continuous subcutaneous insulin infusion (CSII) therapy. METHODS: We collected data from 158 people with T1DM on CSII. COPE-NVI Test was administered and we also collected: hemoglobin A1c (HbA1c), 30 days of self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) records (the most recent). From SMBG and CGM records we computed Kovatchev indexes. We investigated bivariate correlations between HbA1c, indexes and the results of the COPE-NVI Test; the analysis was performed on the total sample and on two sub-groups: men and women. The participants were then divided into clusters and non-parametric tests were performed. RESULTS: Regarding bivariate correlation, at a level of significance of 95%, several statistically significant correlations were found in the total sample and in both men and women sub-groups. Regarding non-parametric tests, we observed statistically significant results in clusters of the total sample and clusters of the sub-group formed by men, divided according to Low Blood Glucose Index (LBGI) risk, showing a different use of certain coping strategies. CONCLUSIONS: Assessing coping strategies preferably used by PWD is useful to select PWD in need of counseling and empowerment-oriented training in order to improve glycemic outcomes and decrease severe hypo/hyperglycemic events.

Diagnostic value of a cytomorphological subclassification of follicular patterned thyroid lesions: a study of 927 consecutive cases with histological correlation.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has proved to be an effective diagnostic tool in patients with thyroid nodules. Several reporting schemes have been suggested to define the risk of malignancy and consequent clinical management. To date, however, among lesions showing a follicular pattern, FNAC is still unable to differentiate between benign and malignant ones. The aim of our study was to evaluate whether a subclassification of follicular cytologic specimens, based on cytoarchitectural patterns, could differentiate categories with a different risk of malignancy, thus improving the clinical management of patients harboring follicular nodules. METHODS: We report a cohort of 927 consecutive cases who underwent thyroid surgery in our hospital between 2000 and 2008. Each patient underwent FNAC before surgery. All the cytologic specimens were divided into five categories (Thy 1: inadequate material, Thy 2: benign, Thy 3: indeterminate, Thy 4: suspicious for malignancy, Thy 5: malignant). Thy3 specimens were further divided into three subcategories (Thy 3a, or "follicular lesions of indeterminate significance": scant colloid, microfollicular pattern, or small clusters of thyrocytes with round nuclei usually without, but sometimes with, minimal cellular pleomorphism; Thy 3b, or "follicular neoplasm": absence of colloid, small clusters, or microfollicles of medium-large sized cell populations arranged in cohesive groups with nuclear overlapping, crowding, and pleomorphisms; and Thy 3c or "Hurthle-cell neoplasm": scant colloid, sheets or clusters of oxyphilic cells). RESULTS: Thy 1 specimens (51 cases on the whole) proved to be malignant in 5.88% (3 cases), Thy 2 specimens (319) in 3.45% (11 cases), Thy 4 specimens (91) in 84.62% (77 cases), and Thy 5 specimens (172) in 98.84% (170 cases). Thy 3 specimens (294 cases) proved to be malignant in 17.35% as a whole, but when divided into the three subcategories, the percentage of malignant cases was significantly different between the Thy 3a group (4.95%) and the Thy 3b and Thy 3c groups (25.0% and 22.77% respectively). CONCLUSIONS: This study supports the National Cancer Institute consensus showing a different risk of malignancy for "follicular lesions of undetermined significance" compared with "follicular neoplasms" and "Hurthle cells neoplasms," which are more suspect for malignancy. This subclassification could improve clinical management of thyroid nodules, helping to better select patients for surgery or follow up.

US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules.

The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (131I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95 degrees C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 +/- 21.5 mL (mean +/- SD), but significantly decreased during follow-up: 19.2 +/- 16.2 at 1 mo (-32.7%; p < 0.001), 15.9 +/- 14.1 mL at 3 mo (-46.4 %; p < 0.001) and 14.6 +/- 12.6 mL at 6 mo (-50.7%; p < 0.001). After treatment, all patients with cold nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 +/- 1.4 to 2.2 +/- 1.9 (p < 0.0001). Radiofrequency was effective and safe in reducing volume by about 50% and compressive symptoms in large benign nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others.