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

INTRODUCTION

Thyroid cancer is the most common endocrine related malignancy in the Philippines. Data showed Filipino patients are at higher risk to develop thyroid malignancy with an increasing incidence annually. Currently, the initial screening test utilized to evaluate thyroid nodules is ultrasonography with studies showing promising results in detecting and evaluating thyroid carcinoma employing the use of the Thyroid Imaging, Reporting and Data System (TIRADS). TIRADS is a standardized classification system to evaluate and characterize thyroid nodules. However, there are studies stating that TIRADS is of limited clinical value for risk stratification of indeterminate cytological results.

The primary objective of this study is to determine the correlation of the results of TIRADS, Fine Needle Aspiration Cytology (FNAC), and histopathology of thyroid nodules among patients who underwent thyroidectomy at Makati Medical Center from January 2016 to March 2020.

This is a retrospective, analytical, observational, cross-sectional study wherein medical records of patients who were diagnosed with thyroid nodules goiter who underwent thyroid ultrasound with TIRADS scoring, Fine needle Aspiration Biopsy (FNAB) and ultimately thyroidectomy were reviewed. The primary endpoint included diagnostic performance of TIRADS classification and the possible factors that may contribute to discordance to FNAB and Histopathology.

One hundred twenty-five patients who underwent thyroidectomy were reviewed. These patients underwent thyroidectomy on the basis of their fine needle aspiration biopsy results. With FNAB as a reference standard, TIRADS had good sensitivity of 100% and low specificity of 27.7% in detecting thyroid malignancy. Patients who had FNAB positive or suspicious for malignancy are 1.37 times more likely to yield a positive TIRADS compared to patients who are FNAB negative (LR+), and 94% less likely to yield a negative TIRADS result (LR-). When TIRADS is positive, the positive predictive value was 31.3% and when TIRADS is negative, the negative predictive value (NPV) was nearly 100%. Overall, the accuracy of TIRADS in thyroid malignancy is 45.6% with ROC area at 0.638, indicating fair discriminative power of TIRADS to differentiate between benign vs malignant thyroid nodules. With histopathology as a reference standard, TIRADS had good sensitivity of 96.3% and low specificity of 33.8%. Patients who are histopathology positive are 1.45 times more likely to yield a positive TIRADS compared to patients who are histopathology negative (LR+), and 89% less likely to yield a negative TIRADS result (LR-). When TIRADS is positive, the positive predictive value was 52.5% and when TIRADS is negative, the negative predictive value (NPV) was 92.3%. Overall, the accuracy of TIRADS in thyroid malignancy is 60.8% with ROC area at 0.65, indicating fair discriminative power to differentiate between benign versus malignant thyroid nodules.

TIRADS classification provides high sensitivity value in detecting thyroid malignancies but has fair discriminative power to differentiate between benign versus malignant thyroid nodules. Factors that are associated with discordant classification between TIRADS and FNAB were seen in those who underwent total thyroidectomy with lymph node dissection, and solid composition. There is insufficient evidence to determine whether any of the patient or nodule characteristics were associated with discordance between TIRADS and histopathology.

INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations. METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine. RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn. CONCLUSION RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.
Humans ; Radiofrequency Ablation/methods* ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Treatment Outcome ; Postoperative Complications/etiology*

Humans ; Thyroid Neoplasms/metabolism* ; Consensus ; Thyroidectomy ; China ; Immunohistochemistry ; Postoperative Period

INTRODUCTION

Papillary thyroid cancer (PTC) is generally considered to be an indolent disease with relatively good prognosis. However, some studies have shown that the Filipino population has a higher risk for disease recurrence compared to non-Filipino patients and hence early identification and management during the follow-up period would be beneficial, especially those in whom risk factors for recurrence were identified.

This study aims to identify determinants for disease recurrence of patients with papillary thyroid carcinoma (as defined by the American Thyroid Association (ATA) guidelines 2015) diagnosed from January 1, 2013-December 31, 2017, seen at the University of Santo Tomas Hospital (USTH) outpatient endocrine clinic and underwent total thyroidectomy with or without radioactive iodine ablation therapy.

Retrospective review of outpatient medical records of 82 patients with PTC who underwent total thyroidectomy with or without radioactive iodine (RAI) therapy and achieved excellent response (ER) to therapy was performed. Baseline clinical profile such as age at diagnosis, sex, family history of thyroid cancer, family history of goiter, histopathology result, serial thyroglobulin (Tg), anti-thyroglobulin (anti-Tg) levels, whole body scan reports, neck ultrasound reports and RAI doses were collected. Logistic regression analysis was used to identify determinants to the development of worsening response.

Of the 82 patients, 18 (21.9%) developed worsening response to therapy. Predictors of poor outcomes identified from previous studies such as age, sex, extent of disease, size and multifocality of tumors, ATA risk classification and initial dynamic risk assessment, RAI therapy, level of thyroid-stimulating hormone (TSH) suppression were analyzed. After logistic regression analysis, there was no significant association between variables and progression to worsening response that were previously identified in other studies.

Even though no significant association between investigated variables and worsening response were identified in this study, previous studies with larger populations that had exhibited positive association should be considered and hence current Philippine guidelines for the management of PTC must still be applied.

BACKGROUND

Thyroid fine-needle aspiration biopsy (FNAB) is widely used for thyroid nodule characterization, with approximately 2.7% of samples classified as "inadequate." Non-diagnostic samples pose limitations, resulting in repeated procedures, and unnecessary diagnostic thyroidectomies. Conventional smear (CS) is commonly the method of choice for cytologic preparation of thyroid FNAB. The cell block technique is an alternative that concentrates cells providing additional material for better evaluation and ancillary testing. While conventional smears are commonly used, introducing routine complementary cell blocks could potentially lower costs associated with repeat procedures and improve patient management.

The study aimed to investigate the diagnostic value of incorporating the cell block technique as adjunct to conventional smear technique in reducing nondiagnostic rates (Bethesda Category I) in thyroid-fine needle aspiration biopsies (FNAB) conducted in 2 private hospitals.

This is a multi-center, retrospective cross-sectional study with 701 samples from 528 adult patients, who underwent thyroid FNAB between January 2020 - September 2022. The primary outcome of interest is the reduction in non-diagnostic rates with the combined use of conventional smears and cell block.

The non-diagnostic rates were significantly higher with cell block technique (28.10%) as compared to conventional smears (16.26%), p-value < .01. The results show that conventional smears have lower non-diagnostic rates. With smear cytology alone, 114 (16.3%) of all samples were nondiagnostic. With the addition of cell block technique, 15 of these samples were reclassified as benign (n = 13), Bethesda III (n = 1) or Bethesda IV (n = 1). The rest of the non-diagnostic samples (n = 99) remained Bethesda I. Overall, the equivalent decrease in non-diagnostic rate was 2.1%.

The combined use of cell block and conventional smears did not significantly decrease nondiagnostic rates in thyroid FNAB. In general, conventional smears demonstrated superior diagnostic efficacy across all Bethesda categories, establishing it as the preferred sampling preparation method for thyroid FNAB. Cell blocks should be considered a supplementary technique, particularly in cases where ancillary methods like immunohistochemistry or molecular testing are needed.

Familial Adenomatous Polyposis (FAP) is a multi-tumoral syndrome that includes neoplasms in the duodenum, brain, pancreas and thyroid. The Cribriform Morular Variant (CMV) is a rare form of Papillary Thyroid Cancer seen in patients with FAP. Presented here is a 32 year old female who initially presented with an anterior neck mass followed years later by a rectal mass. She was diagnosed with FAP and colorectal adenocarcinoma and underwent total proctocolectomy with end ileostomy. She subsequently underwent a total thyroidectomy which revealed CMV Papillary Thyroid Carcinoma (CMV-PTC). Since FAP can have diverse presentations, a high index of suspicion is needed in order to make an earlier diagnosis to reduce potential morbidity and mortality. Papillary thyroid carcinoma can predate colonic polyposis. Identifying CMV-PTC early on can serve as an opportunity diagnose FAP early.