Introduction: Medullary thyroid carcinoma (MTC) comprises sporadic and hereditary forms, the latter commonly associated with multiple endocrine neoplasia type 2 (MEN2) which is identifiable through genetic screening of germline RET protooncogene. We compared the clinicopathological features and outcomes of hereditary and sporadic MTC in our single centre. Methodology: We conducted a retrospective audit of patients with MTC from 2000 to 2026. Patients were classified as either hereditary or sporadic based on genetic testing and/or family history of MTC/MEN2A syndrome. Variables analyzed included age at diagnosis, mode of presentation, pre-operative calcitonin, tumor size, lymph node (LN) involvement, post-operative biochemical cure, repeat surgery and presence of structural residual/recurrent disease. Results: A total of 57 patients were included (18 hereditary [31.6%], 39 presumed sporadic [68.4%]) with a median follow-up of 7.5 years (IQR 1.5–12.4). Hereditary MTC was diagnosed at a significantly younger age than sporadic MTC (33.0 vs. 44.7 years, p = 0.010) where 33% of the cases were diagnosed via screening detection whereas sporadic MTC more commonly presented with symptomatic neck swelling (84.6% vs. 50.0%, p = 0.008). There were no significant differences in median pre-operative calcitonin (513.5 vs. 1148.0 pg/mL, p = 0.101), tumor size (24.5 vs. 22.5 mm, p = 0.301), or LN involvement (41.7% vs. 61.5%, p = 0.307) between hereditary and sporadic MTC. Long-term outcomes were also comparable, with no differences in biochemical status, need for repeat surgery or residual/recurrent structural disease. Conclusion Hereditary MTC presents earlier and is more frequently detected due to screening, whereas sporadic MTC often presents symptomatically. Long-term outcomes are not primarily determined by hereditary status alone. Early access to RET mutation testing with a view to initiating prophylactic treatments rather than post detection surgery may improve disease burden.
Thyroid Neoplasms ; Cohort Studies

Introduction: Parathyroid carcinoma is a rare endocrine malignancy found in 1–5% of patients with primary hyperparathyroidism. It commonly presents with severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. We report a challenging case of parathyroid carcinoma presenting with refractory hypercalcemia with incidental papillary thyroid microcarcinoma. Case: A 63-year-old female with hypertension, diabetes mellitus, dyslipidemia, and ischemic heart disease had been followed for primary hyperparathyroidism since 2014 (PTH5.5 pmol/L, calcium range 2.3–4.7 mmol/L). Initial neck ultrasound was suggestive of parathyroid adenoma over left side, but parathyroid scintigraphy failed to localize a lesion. She refused surgical intervention initially until April 2025, then she later agreed. Re-evaluation prior to operation revealed PTH level 76 pmol/L, and repeated parathyroid scintigraphy showed mild sestamibi avid uptake on left thyroid nodule. While awaiting surgery, she was admitted with a hypercalcemic crisis (serum calcium 3.7–5.38 mmol/L), complicated with acute kidney injury. Repeated ultrasound neck revealed extrathyroidal lesion adjacent to inferior pole of left thyroid (1.6 × 1.7 × 1.2 cm). She required aggressive intravenous hydration, intravenous pamidronate, calcitonin, and Denosumab to optimize her calcium level peri-operatively. She underwent left neck exploration with en-bloc left inferior parathyroidectomy, left hemithyroidectomy, and central neck dissection in November 2025. Histopathological examination confirmed parathyroid carcinoma (pT3N1) with nodal metastasis (1/4 lymph nodes positive) and an incidental papillary thyroid microcarcinoma measuring 1 mm (pT1a). Conclusion This case highlights the challenges of perioperative hypercalcemia management in parathyroid carcinoma. Effective preoperative control often requires multiple treatment modalities. Severe refractory hypercalcemia and high PTH level should raise a high index of suspicion for malignancy. Early complete resection is the cornerstone of treatment and is associated with optimal outcomes.
Papillary Thyroid Microcarcinoma ; Calcium ; Parathyroid Neoplasms

Introduction: Medullary thyroid carcinoma (MTC) has the highest familial predisposition syndrome of any hereditary cancer syndrome. The most common subtype of hereditary MTC is multiple endocrine neoplasia type 2A (MEN2A), which is an autosomal dominant syndrome characterized by MTC, pheochromocytoma, and primary hyperparathyroidism (HPP). This study evaluates the genotypic distribution, phenotypic manifestations, and clinical characteristics of MEN2A within a retrospective MTC cohort. Methodology: A retrospective audit of MTC patients was conducted at a tertiary centre. Patients with clinically or genetically confirmed hereditary MTC were identified for further analysis. Electronic medical records were reviewed for demographic data, RET germline mutations, occurrence of pheochromocytoma and HPP, laterality of disease, and documented surgical interventions. Results: In all, 18 patients (31.6%) were classified as hereditary from a cohort of 57 patients with a median age at diagnosis of 29.2 years. Among genetically confirmed cases with available variant data (n = 11), mutations predominantly involved exon 11 codon 634 (90.9%, n = 10), including p.Cys634Arg (n = 4), p.Cys634Tyr, and p.Cys634Ser, with one codon 618 mutation. Extrathyroidal manifestations were common. Pheochromocytoma occurred in 50.0% (n = 9), of which 77.8% (n = 7) were bilateral. Most patients underwent adrenalectomy, including bilateral procedures in those with bilateral disease. HPP was identified in 44.4% (n = 8), managed with selective parathyroidectomy. Both pheochromocytoma and HPP were present in 22.2% (n = 4), while isolated MTC occurred in 27.8% (n = 5). Conclusion Hereditary MTC in our cohort is predominantly associated with high-risk codon 634 RET mutations and demonstrates substantial penetrance of pheochromocytoma and HPP. The high frequency of bilateral adrenal involvement highlights the importance of systematic biochemical surveillance and appropriately timed surgical management in MEN2A. A nationwide registry would be timely.
Humans ; Multiple Endocrine Neoplasia Type 2a ; Thyroid Neoplasms

Introduction: Discordant thyroid function tests (TFTs), characterized by elevated free thyroxine 4 (FT4) with non-suppressed thyroid-stimulating hormone (TSH), pose a significant diagnostic challenge. Differentiating between Resistance to Thyroid Hormone (RTH) and TSH-secreting pituitary adenoma (TSH-oma) is essential, as management strategies differ substantially. Case: A female with a history of hyperthyroidism diagnosed in 2011 was treated with antithyroid drugs for 1 year before defaulting on follow-up. She was later found to have discordant TFTs at a private centre, where a brain computed tomography scan was reportedly normal. She was referred to our centre for optimization of thyroid function prior to planned thyroidectomy for a solitary large right thyroid nodule measuring 4.2 × 2.8 × 4.7 cm. Fine-needle aspiration cytology demonstrated a benign follicular lesion (Bethesda II). Despite restarting antithyroid medication, she remained clinically euthyroid with no overt thyrotoxic symptoms apart from intermittent palpitations without documented tachycardia. Antithyroid therapy was discontinued. Serial TFTs across multiple assay platforms consistently demonstrated elevated FT4 with inappropriately normal TSH levels. Thyroid autoantibodies, including TSH receptor and anti-thyroid peroxidase antibodies, were negative. Pituitary magnetic resonance imaging showed no evidence of adenoma, and serum α-subunit level was normal (0.3 ng/ mL), making TSH-oma unlikely. Dynamic testing was not performed as thyrotropin-releasing hormone stimulation was unavailable at our centre, while T3 suppression testing was deemed inappropriate due to symptomatic palpitations. Family screening was not possible as the patient was not in contact with her relatives. In the absence of pituitary pathology and given her largely euthyroid clinical status, RTH was considered the most likely diagnosis. Conclusion This case highlights the importance of considering RTH in patients with persistent discordant TFTs, particularly when clinical findings do not correlate with biochemical abnormalities. Early recognition and appropriate pituitary evaluation are essential to prevent misdiagnosis and avoid unnecessary antithyroid therapy or thyroidectomy.
Pituitary Neoplasms ; Thyroid Hormones ; Thyrotropin

A 61-year-old woman presented with a 2-month history of non-painful left eye proptosis. Imaging studies showed a superotemporal mass in the left orbit with intracranial extension. Surgical excision of the orbitocranial mass was performed and histopathologic examination revealed metastatic papillary thyroid carcinoma. She subsequently underwent total thyroidectomy. Orbital metastasis from thyroid carcinoma is rare and can be the initial manifestation of occult disease in 63% of cases.

OBJECTIVES: Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of WNT10A gene knockdown in PTC cell proliferation, invasion, and metastasis. METHODS: The expression of WNT10A in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure WNT10A mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by WNT10A were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway. RESULTS: WNT10A mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both P<0.01). The real-time RT-PCR result showed that WNT10A mRNA expression in PTC tissues was high than that in adjacent tissues (P<0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (P<0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. WNT10A knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all P<0.01). WNT10A silencing also reduced migration and invasion abilities in both cell lines. In vivo, WNT10A knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that WNT10A knockdown downregulated the expression of key genes (STAT3, MAPK8, TNFRSF21, and AKT2) in this pathway. CONCLUSIONS WNT10A is highly expressed in PTC and is associated with tumor proliferation, invasion, and metastasis. Its tumor-promoting effects may be mediated through suppression of the Tec kinase signaling pathway.
Humans ; Cell Proliferation ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/metabolism* ; Animals ; Wnt Proteins/metabolism* ; Neoplasm Invasiveness ; Mice ; Cell Line, Tumor ; Female ; Male ; Mice, Nude ; Apoptosis ; Lymphatic Metastasis ; Middle Aged ; Cell Movement ; Adult

OBJECTIVES: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m⁶A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m⁶A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m⁶A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy. METHODS: Expression profiles of m⁶A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m⁶A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis. RESULTS: By comparing TCGA and GSE130512 cohorts, it was found that circulating m⁶A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect. CONCLUSIONS Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m⁶A modification of pri-miR-139, but its clinical value needs further verification.
Humans ; MicroRNAs/metabolism* ; Thyroid Cancer, Papillary/metabolism* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism* ; Thyroid Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasm Metastasis ; Adenosine/genetics* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Cadherins/metabolism* ; Cell Proliferation ; Zinc Finger E-box-Binding Homeobox 1/genetics*

Objective: Intrathyroid thymic carcinoma（ITTC） is a rare thyroid tumor that lacks typical clinical manifestations and imaging features, making preoperative diagnosis challenging.The primary treatment for ITTC is radical surgery; however, the effectiveness of adjuvant radiotherapy and chemotherapy post-surgery is not well-established. This paper presents a case of ITTC , analyzing the clinical data and correlating it with the literature to explore the clinical manifestations, diagnostic approach, treatment, and prognosis of ITTC.
Humans ; Prognosis ; Thymoma ; Thymus Neoplasms/diagnosis* ; Thyroid Neoplasms/pathology*

Objective:To observe the clinical progression of low-risk papillary thyroid microcarcinoma（LR-PTMC）, analyze the influencing factors of its oncological outcomes, and explore the feasibility of active surveillance（AS） of LR-PTMC. Methods:This study adopted a prospective observational research design. A total of 85 subjects diagnosed with LR-PTMC during health checkup in Health Management Center of our hospital from March 2021 to October 2022 were enrolled as the research subjects, for at least 2 years of AS follow-up observation. The clinical progress and oncological outcomes were recorded, disease progression was defined as any increase in nodule diameter ≥3 mm or the appearance of new lesions or lymph node metastasis or distant metastasis, and the oncological outcome was use disease progression defining. Cox proportional hazards regression model was used to analyze the influencing factors of oncological outcomes in LR-PTMC patients. Results:A total of 85 LR-PTMC patients who underwent physical examinations were included in this study. The median follow-up time was 2 years, and a total of 23 patients（27.06%） experienced disease progression. Among them, 18 patients（21.18%） had enlarged lesions（any nodule diameter increased by ≥3 mm）, and 5 patients（5.88%） had abnormal or metastatic cervical lymph nodes. The 2-year cumulative disease progression rate was 9.41%. The incidence age of LR-PTMC patients was younger, with a higher proportion of ≤45 years old. The proportion of baseline nodules with a maximum diameter greater than 5 mm is higher, and the proportion of baseline TPO Ab positivity was higher. Ultrasound showed a higher proportion of microcalcifications compared to the non progression group, and the differences were statistically significant（all P<0.05）. Multivariate Cox proportional hazards regression analysis showed that age of onset ≤45 years RR 95% CI 1.052（1.018-1.088） and ultrasound showing microcalcifications RR 95% CI 3.361（1.379-8.194） were independent risk factors affecting disease progression during AS in LR-PTMC patients（P<0.05）. Conclusion:Most LR-PTMC patients maintain stable lesion size and low lymph node metastasis rate during the AS process, with good oncological outcomes in the short term. AS can be considered as a safe and effective alternative to surgical treatment for LR-PTMC patients. But for patients with onset age ≤45 years and microcalcifications, the follow-up interval can be shortened for close observation.
Humans ; Thyroid Neoplasms/pathology* ; Disease Progression ; Prospective Studies ; Carcinoma, Papillary/pathology* ; Female ; Male ; Middle Aged ; Adult ; Watchful Waiting ; Lymphatic Metastasis ; Proportional Hazards Models ; Risk Factors

Objective:To evaluate the feasibility, safety, and short-term efficacy of robot-assisted unilateral axillary approach for partial or total thyroidectomy without inflation. Methods:A retrospective analysis was performed on the clinical data of 98 patients who underwent gasless unilateral axillary approach robot-assisted resection of bilateral thyroid lesions at Sun Yat-sen University Cancer Center between October 2022 and October 2024. Perioperative indicators were recorded and compared among patients undergoing different surgical approaches（total thyroidectomy vs. bilateral partial thyroidectomy） and with different body mass index（BMI） values, including operative time, intraoperative blood loss, number of lymph nodes dissected, incidence of postoperative hoarseness, incidence of postoperative hypocalcemia, and other postoperative complications. Results:A total of 98 patients were included, of whom 78.57% were female, with a median age of 39 years（interquartile range[IQR]: 35-49） and a median BMI of 24.08 kg/m²（IQR: 21.43-25.98）. The median intraoperative blood loss was 32.14 mL（IQR: 20.00-50.00）, the median operative time was 130.0 minutes（IQR: 104.80-150.30）, and the median hospital stay was 2.01 days（IQR: 1.00-2.00）. The most common postoperative complication was transient hypocalcemia, with an incidence of 16.32%. There were no cases of permanent recurrent laryngeal nerve palsy or conversion to open surgery. Compared with the non-total thyroidectomy group, the total thyroidectomy group had a significantly longer operative time（135.10±33.28 min vs 120.30±30.53 min, P=0.033）. Subgroup analysis based on BMI showed no statistically significant differences in operative time, hospital stay, drainage volume, or incidence of hypocalcemia between patients with BMI≥25 kg/m² and those with BMI<25 kg/m². Conclusion:The gasless unilateral axillary approach for robot-assisted partial or total thyroidectomy demonstrates favorable safety, cosmetic outcomes, and feasibility. Appropriate selection of surgical techniques and meticulous protection of critical structures during the procedure can further reduce the risk of complications and optimize therapeutic outcomes.
Humans ; Thyroidectomy/methods* ; Retrospective Studies ; Female ; Robotic Surgical Procedures/methods* ; Male ; Adult ; Middle Aged ; Axilla/surgery* ; Operative Time ; Postoperative Complications ; Thyroid Neoplasms/surgery* ; Thyroid Gland/surgery* ; Lymph Node Excision