Background: Molecular testing is recommended to refine risk stratification in indeterminate thyroid nodules (Bethesda III–IV), but data on dual-gene (BRAF and RAS) testing using fresh FNA washout specimens are limited. We aimed to evaluate the performance of BRAF and RAS mutation analysis from fresh thyroid FNA washout material, with a focus on indeterminate cytology. Methods: We retrospectively analyzed 1139 patients who underwent washout-based molecular testing between May 2022 and October 2024 at a tertiary endocrine center. Of these, 307 had available histopathologic results after surgery. Primary outcomes were sample adequacy, mutation spectrum, and diagnostic metrics (sensitivity, specificity, PPV, NPV, and accuracy). Analyses were repeated under two assumptions that classified borderline/low-risk neoplasms as benign vs. malignant, and within the Bethesda III–IV subset. Results: Adequate material for molecular analysis was obtained in 1037/1139 samples (90.9%). In the operated cohort (n = 307), malignant lesions comprised 31.9% and low-risk neoplasms 8.5%. When borderline lesions were considered benign, mutation positivity yielded a sensitivity of 48.0%, a specificity of 89.6%, a PPV of 75.9%, an NPV of 71.9%, and an accuracy of 72.9%. In Bethesda III–IV nodules (n = 153), sensitivity, specificity, and accuracy were 41.0%, 85.2%, and 66.0% (malignant assumption). Isolated BRAF positivity showed high specificity (~96.7%) with modest sensitivity. Conclusions: Our findings extend current diagnostic approaches by showing that dual-gene (BRAF and RAS) testing from fresh FNA washouts is technically feasible (≥90% adequacy) and provides high specificity with modest sensitivity for malignancy in indeterminate nodules. In settings lacking comprehensive commercial panels, this low-complexity approach offers a practical adjunct to cytology and imaging for preoperative decision-making.

Background/Objectives: This study aimed to evaluate the diagnostic utility of 24 h urinary aldosterone (uAldo) measurements in patients with suspected primary aldosteronism (PA) and to explore its potential utility in guiding individualized clinical decisions. Methods: We examined 40 patients with suspected PA who underwent screening, confirmatory testing and 24 h uAldo assessment at a tertiary endocrinology center. Confirmatory tests were performed per standardized protocols. Patients were classified into three groups based on uAldo levels derived from receiver operating characteristic (ROC) analysis: Group 1 (13.6 μg/24 h). Diagnostic performance was evaluated using sensitivity, specificity, and area under the curve (AUC). Results: uAldo levels were significantly higher in patients with positive confirmatory tests (16.3 μg/24 h vs. 5.5 μg/24 h, p < 0.001). A cut-off of >8.7 μg/24 h showed 89% sensitivity and 91% specificity (AUC: 0.95), while >13.6 μg/24 h yielded 91% sensitivity and 86% specificity (AUC: 0.97). Patients in Group 2 were managed solely with medical therapy, with no need for invasive procedures. Group 3 patients had higher blood pressure, higher uAldo levels, and more frequent hypokalemia. Adrenal venous sampling and surgery were more common in Group 3, with histological PA confirmation in all operated patients. Conclusions: The 24 h uAldo measurement demonstrated promising diagnostic performance in this cohort. The proposed cut-offs may help support patient stratification and clinical decision-making in patients with suspected PA. However, because confirmatory testing served as the reference standard, these findings should be considered exploratory and require external validation in larger multicenter studies before incorporation into routine diagnostic algorithms.

Background/Objectives: Fine-needle aspiration biopsy (FNAB) is the primary diagnostic procedure for the evaluation of thyroid nodules. Although considered safe and minimally invasive, its immediate systemic biochemical effects, particularly those related to oxidative stress and mechanical tissue injury, remain insufficiently characterized. This study aimed to evaluate the acute systemic impact of FNAB on oxidative stress parameters and to determine whether these changes correlate with cytological malignancy risk. Methods: A total of 208 patients undergoing ultrasound-guided FNAB for a solitary thyroid nodule were prospectively included. Venous blood samples were collected in the supine position immediately before and within 1 min after the procedure. Thiol–disulfide homeostasis parameters were measured using an automated spectrophotometric method, and ischemia-modified albumin (IMA) levels were analyzed concurrently. Pre- and post-procedural values were compared using the Wilcoxon signed-rank test. Associations between oxidative stress markers and Bethesda cytological categories were assessed using Spearman’s correlation analysis. Results: Native thiol and IMA levels demonstrated statistically significant changes following FNAB, whereas total thiol, disulfide levels, and derived thiol–disulfide ratios remained unchanged. The reduction in IMA levels was predominantly observed in lower-risk cytological categories. No significant correlations were identified between oxidative stress parameters and Bethesda-based malignancy risk. Conclusions: FNAB induces only minor and transient alterations in selected systemic oxidative stress markers, which are clinically inconsequential. The observed changes in native thiol and IMA levels appear to reflect short-term procedural effects rather than malignancy-associated redox alterations. These findings support the systemic safety of FNAB and emphasize the need for careful temporal standardization when interpreting circulating oxidative biomarkers in thyroid nodule research.

Background and Objectives: Medullary thyroid carcinoma is a rare neuroendocrine malignancy, with sporadic and hereditary forms accounting for 75% and 25% of cases, respectively. This study compares the clinicopathological features of sporadic medullary thyroid carcinoma (sMTC) and hereditary medullary thyroid carcinoma (hMTC) using real-world data to provide risk factors that aid in the early detection of the disease. Materials and Methods: The retrospective study comprised 77 patients with confirmed MTC treated at a tertiary referral center between January 2019 and December 2024. Patients were classified as hMTC (n = 11) or sMTC (n = 66) based on RET proto-oncogene (RET) genetic testing, whereas harboring a germline RET mutation indicated hMTC. Demographic, clinical, laboratory, radiological, histopathological, and genetic data were collected. Results: hMTC patients were significantly younger at diagnosis, with a comparable gender distribution (p = 0.738), and more often had a previous case of MTC within the family history. Pheochromocytoma occurred exclusively in hMTC. Multicentric tumors were more frequent in hMTC, and non-diagnostic Bethesda I cytology was higher in hMTC. Conclusions: While confirming established differences, this study provides detailed pre-operative diagnostic parameters and surgical approaches that can guide clinical decision-making in resource-limited settings where genetic testing may not be immediately available.