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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. [ABSTRACT FROM AUTHOR]

Introduction: Calcitonin is themost specificmarker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced fromthe last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results: Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level =16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion: Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis. [ABSTRACT FROM AUTHOR]

Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+ /K+ - adenosine triphosphatase (H+ /K+ -ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+ /K+ -ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+ /K+ -ATPase and the IL17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+ /K+ -ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+ /K+ -ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management. [ABSTRACT FROM AUTHOR]

Introduction. Detecting hypogonadism, which is important in the general population, becomes crucial in patients with sexual dysfunctions, because hypogonadism can have a causal role for them and testosterone (T) substitution represents a milestone for the therapy. Aim. No inventories are available for the screening of hypogonadism in patients with sexual dysfunction. We wished to set up a brief structured interview providing scores useful for detecting hypogonadism defined as low total T (<10.4 nmol/L, 300 ng/dL) in a symptomatic population (sexual dysfunction). Methods. A minimum set of items was identified within a larger structured interview through iterative receiver-operating characteristic curve analysis, with assessment of sensitivity and specificity for hypogonadism in a sample of 215 patients. Main Outcome Measures. Sensitivity and specificity were verified in a further sample of 664 patients. Correlation of test scores with prostate-specific antigen (PSA), testis volume, and others clinical and psychological parameters, was assessed for concurrent validity. Results. In the validation sample, the final 12-item version of the interview (ANDROTEST ©) had a sensitivity and specificity of 68% and 65%, in detecting low total T (<10.4 nmol/L) and of 71% and 65%, in the screening for low free T (<37 pmol/L). Furthermore, patients with a pathological test (i.e., score >8) showed higher prevalence of hypogonadism-related signs, such as lower testis volume and higher depressive symptoms. Finally, when only younger patients (<54 years, which represents the median age of the sample) were considered, Log10 [PSA] levels were significantly lower in those with ANDROTEST © score >8. Conclusion. ANDROTEST © is a quick and easy-to-administer interview that provides scores for the screening of male hypogonadism in patients with sexual dysfunction. Corona G, Mannucci E, Petrone L, Balercia G, Fisher AD, Chiarini V, Forti G, and Maggi M. ANDROTEST ©: A structured interview for the screening of hypogonadism in patients with sexual dysfunction. J Sex Med 2006;3:706–715. [ABSTRACT FROM AUTHOR]

Objective: Decreased survival and higher cardiovascular morbidity have been recently reported in a UK cohort of 61 RTHβ patients, but there is no evidence from other countries., Design: Retrospective cohort study from an historical group of 284 Italian RTHβ patients, diagnosed between 1984 and 2023., Methods: We collected data on diagnosis of 284 cases and longitudinal data of 249 RTHβ who carried heterozygous pathogenic variants in the THRB gene. We studied how thyroid function and recognized risk factors for cardiovascular disease, such as hypertension and diabetes, affected overall mortality and major cardiovascular events., Results: The cumulative prevalence of sinus/supraventricular tachycardia and atrial fibrillation was 40% and 18%, respectively. FT4 values 57% higher than the upper limit of normal were associated with premature cardiovascular manifestations. Major cardiovascular events (MACEs) occurred in RTHβ patients at a median age (IQR) of 59.4 years (50.4-66.4) and early mortality resulted in a mean of 11 years of life lost. While at univariable analysis hypertension, dyslipidemia, high fasting glucose/diabetes were also associated with MACEs, at multivariable analysis only age at diagnosis, increased fT4 levels, and male gender remained significantly associated with MACEs and age at diagnosis and higher fT4 levels with mortality. Previous thyroidectomy or radioiodine therapy had no statistically significant effect in the prevention of major cardiovascular events or all-cause mortality., Conclusions: These data should raise the general awareness on the cardiovascular risk and prompt a proactive cardiovascular monitoring in RTHβ, especially in men and those with fT4 levels above 30 pmol/L., Competing Interests: Conflict of interest: No competing financial interests exist., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Context: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management., Objective: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone., Design: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database., Patients: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies., Interventions: Serum Tg levels assessed at 1-year follow-up visit., Main Outcome Measure: Detection of structural disease within 5 years of follow-up., Results: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease., Conclusions: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)