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In primary hyperparathyroidism, postoperative hypocalcemia can be exacerbated by magnesium deficiency. However, the significance of magnesium homeostasis in surgery for secondary hyperparathyroidism is unknown. In this study, 268 consecutive adult patients on renal replacement therapy who underwent parathyroidectomy for secondary hyperparathyroidism were included for analysis. We found that about one fifth presented with hypomagnesemia (5.6%) or hypermagnesemia (14.6%). Hypomagnesemia was associated with lower calcium levels and longer postoperative hospital stays. Hypermagnesemia was associated with higher calcium-phosphorus products and lower parathyroid hormone levels. In multivariate analysis, patient age, alkaline phosphatase, and osteocalcin were independent predictors of prolonged stay after parathyroidectomy. There was a positive correlation between serum magnesium levels and severity of itching in these patients. Calcium-phosphorus products and serum magnesium levels were independently associated with pruritus. In conclusion, magnesium abnormalities play a minor role in hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism. Patients with higher serum magnesium levels had greater severity of pruritus.

Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.

While an increasing number of patients now undergo lobectomy for low-risk differentiated thyroid cancer, a subset of patients require completion thyroidectomy to facilitate radioactive iodine therapy. Completion thyroidectomy is generally as safe as the initial operation, but a previous study showed that a longer hospitalization is required for completion thyroidectomy. In this study, we reviewed 61 consecutive patients who had been treated with an initial lobectomy and subsequent completion thyroidectomy at our institution from 2012 to 2021. We detected a changepoint in 2016 for the proportion of patients who were treated with a thyroid lobectomy (Pettitt’s test P= 0.049). The rate of completion thyroidectomy remained stable throughout the study period. There was no difference in operating time, intraoperative blood loss, perioperative drop in calcium levels, and postoperative hospital stay between surgeries. The patients reported higher pain scores on the day of operation (P= 0.007) and the postoperative day 1 (P= 0.022). Occult papillary microcarcinomas were identified in the contralateral thyroid lobe in 13 (21%) patients. Multifocality was the only predictor for residual malignancy in multivariate regression. In conclusion, patients with differentiated thyroid cancer experienced more pain in the immediate postoperative period following completion thyroidectomy. Hospital stays do not change with appropriate opioid-free pain control.

Purpose: ATP-citrate lyase (ACLY) is a critical enzyme at the intersection of glucose and lipid metabolism. ACLY is often upregulated or activated in cancer cells to accelerate lipid synthesis and promote tumor progression. In this study, we aimed to explore the possibility of utilizing ACLY inhibition as a new strategy in the treatment of thyroid cancer. Methods: Bioinformatics analysis of the public datasets was performed. Thyroid cancer cells were treated with two different ACLY inhibitors, SB-204990 and NDI-091143. Results: Bioinformatics analysis revealed that ACLY expression was increased in anaplastic thyroid cancer. In thyroid cancer cell lines FTC-133 and 8505C, ACLY inhibitors suppressed monolayer cell growth and clonogenic ability in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that ACLY inhibitors increased the proportion of sub-G1 cells in the cell cycle and the number of annexin V-positive cells. Immunoblotting confirmed caspase-3 activation and PARP1 cleavage following treatment with ACLY inhibitors. Compromised cell viability could be partially rescued by co-treatment with the pan-caspase inhibitor Z-VAD-FMK. Additionally, we showed that ACLY inhibitors impeded three-dimensional growth and cell invasion in thyroid cancer cells. Isobolograms and combination index analysis indicated that ACLY inhibitors synergistically potentiated the cytotoxicity rendered by sorafenib. Conclusions: Targeting ACLY holds the potential for being a novel therapeutic strategy for thyroid cancer.

Objective:Extrathyroidal extension may not be accurately recognized during thyroidectomy and can increase the risk of positive margins and even recurrence. This study aimed to investigate the preoperative factors associated with extrathyroidal extension. Methods:We analyzed 887 patients with papillary thyroid cancer (PTC) who underwent surgery in the period of 2005–2017. Binary logistic regression analyses and generalized additive models were used to identify associations. Results:Minimal extrathyroidal extension was present in 233 (26%) patients and advanced extrathyroidal extension was found in 60 (7%) patients. Age, BMI, and tumor size were independent predictors of all or advanced extrathyroidal extension. Among the 493 patients whose BRAF mutation status was available, age (OR = 1.025), BMI (OR = 1.091), tumor size (OR = 1.544), and BRAFV600E mutation (OR = 2.311) were independently associated with extrathyroidal extension. Conclusions:Older age, a greater BMI, a larger tumor size, and presence of the BRAFmutation were predictive of extrathyroidal extension. These factors should be taken into consideration in decision-making before surgery is performed.

Objective:Extrathyroidal extension may not be accurately recognized during thyroidectomy and can increase the risk of positive margins and even recurrence. This study aimed to investigate the preoperative factors associated with extrathyroidal extension. Methods:We analyzed 887 patients with papillary thyroid cancer (PTC) who underwent surgery in the period of 2005–2017. Binary logistic regression analyses and generalized additive models were used to identify associations. Results:Minimal extrathyroidal extension was present in 233 (26%) patients and advanced extrathyroidal extension was found in 60 (7%) patients. Age, BMI, and tumor size were independent predictors of all or advanced extrathyroidal extension. Among the 493 patients whose BRAF mutation status was available, age (OR = 1.025), BMI (OR = 1.091), tumor size (OR = 1.544), and BRAFV600E mutation (OR = 2.311) were independently associated with extrathyroidal extension. Conclusions:Older age, a greater BMI, a larger tumor size, and presence of the BRAFmutation were predictive of extrathyroidal extension. These factors should be taken into consideration in decision-making before surgery is performed.

The tumor-promoting or tumor-suppressing role of tumor-associated lymphocytes remains a subject of debate. We examined thyroid cancer data from The Cancer Genome Atlas in an attempt to define the relationship between lymphocyte infiltrates and clinical and molecular presentations.

Cellular retinoic acid-binding protein 2 (CRABP2) participates in retinoid partitioning between different nuclear receptors. Recently, we identified that CRABP2 is one of the progression-associated genes in thyroid cancer. To explore the prognostic and functional significance of CRABP2, immunohistochemical analysis was performed in thyroid tissues and neoplasms. Overexpression of CRABP2 was observed in malignant thyroid neoplasms but not in benign thyroid lesions. CRABP2 expression was an independent predictive factor for recurrence-free survival in patients with differentiated thyroid cancer. Knockdown of CRABP2 reduced the sensitivity of thyroid cancer cells to retinoic acid. Importantly, CRABP2 expression in thyroid cancer cells was associated with epithelial–mesenchymal transition properties, including anoikis resistance, migration, and invasion capacity. Furthermore, invasion promoted by CRABP2 was mediated at least partly by the integrin/focal adhesion kinase/AKT pathway. In summary, CRABP2 expression is upregulated in thyroid cancer with adverse prognostic implications. The invasion-stimulating effects appear independent of canonical retinoic acid signaling and may serve as a potential therapeutic target.