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

Parathyroid carcinoma is a rare endocrine malignancy with an indolent course but a high risk of recurrence. Diagnosis remains challenging, requiring integration of clinical, biochemical, radiologic, and histopathologic findings. We report a young patient presenting with primary hyperparathyroidism complicated by multiple pathologic fractures and chronic renal failure. Despite initial surgical and medical management, late aggressive recurrence occurred, resulting in significant systemic complications. This case highlights the need for vigilant long-term surveillance and improved diagnostic and therapeutic strategies.

Introduction: Giant parathyroid adenomas (GPAs), defined as lesions >3.5 g, are rare. Their size, biochemical severity, and compressive features often mimic carcinoma, creating diagnostic and surgical challenges. Case: A 33-year-old female was incidentally found to have hypercalcemia during evaluation after her newborn developed severe hypocalcemic seizures requiring NICU admission. Maternal calcium was 2.95 mmol/L with hypophosphatemia. Subsequent reviews showed persistent hypercalcemia (3.15–3.3 mmol/L), hypophosphatemia (0.32– 0.51 mmol/L), and markedly elevated intact parathyroid hormone (85–96 pmol/L). She had vitamin D deficiency, very high alkaline phosphatase (1,329 U/L), and progressive bone pain with reduced mobility. Bone mineral density revealed Z scores of −2.9 (hip) and −3.3 (lumbar spine). Multiphase computed tomography demonstrated a multilobulated 6.9 cm mass extending from C5 to T2, compressing the esophagus and raising suspicion for carcinoma. Endoscopic evaluation excluded mucosal invasion. She underwent en bloc left inferior parathyroidectomy with hemithyroidectomy. Intraoperative parathyroid hormone fell from 41.7 to 13.4 pmol/L, confirming complete excision. The gland measured 65 × 20 × 15 mm and weighed 18.4 g. Histopathology revealed a hypercellular parathyroid tumor with endocrine atypia but no invasion, consistent with a giant adenoma. Postoperatively, calcium was initially stable (1.99 mmol/L at discharge) but fell to 1.68–1.82 mmol/L at 2 weeks despite high-dose supplementation. Hypocalcemia persisted for 6 weeks, consistent with delayed hungry bone syndrome, likely precipitated by preoperative vitamin D deficiency, markedly elevated alkaline phosphatase, and low bone mineral density. With intensive supplementation, calcium gradually stabilized, and symptoms improved. Conclusion GPAs can closely mimic carcinoma, with endocrine atypia complicating histopathological interpretation. This case illustrates both diagnostic overlap and the unusual, delayed onset of hungry bone syndrome, emphasizing the need for preoperative risk assessment, correction of metabolic deficiencies, and extended postoperative monitoring. Rare presentations such as delayed hungry bone syndrome refine management strategies and improve outcomes in primary hyperparathyroidism.
Parathyroid Neoplasms

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: Parathyroid carcinoma (PC) is an exceedingly rare malignancy. Definitive surgical management with en bloc resection is crucial for cure, but the post-operative course can be complicated by profound metabolic derangements, most notably hungry bone syndrome (HBS). We report a case of PC in a 15-year-old female to highlight the challenges in perioperative management. Case: A 15-year-old female presented with a painless, palpable neck mass. There is no family history of note. Investigations revealed severe primary hyperparathyroidism (PHPT) with a corrected calcium of 3.4 mmol/L and an elevated intact parathyroid hormone level of 118.6 pg/mL. Alkaline phosphatase was markedly elevated at 1,168 U/L. Ultrasound, computed tomography neck, and a sestamibi scan identified a large, lobulated 4.7-cm mass posterior to the right thyroid lobe, suspicious of malignancy. Bone mineral density of the forearm was severely diminished, with a Z-score of -6.6. The patient underwent right hemithyroidectomy and parathyroidectomy with intraoperative neural monitoring. Intraoperative parathyroid hormone levels dropped from a pre-excision level of 120.1–16.5 pg/mL 5 minutes post-excision, confirming complete resection of the hyperfunctioning tissue. Histopathological examination confirmed the diagnosis of PC, demonstrating lymphovascular invasion and clear resection margins. The Ki-67 proliferation index was 5%. Post-operatively, the patient developed hypocalcemia, with corrected calcium dropping to a nadir of 1.95 mmol/L. This was managed with intensive calcium and activated vitamin D supplementation. At 10 months post-surgery, the patient continues to require supplementation for persistent hypocalcemia. Surveillance ultrasound at 3 months showed no evidence of recurrence, and she is planned for ongoing annual monitoring. Conclusion This case illustrates the need for a high index of suspicion for PC in young patients with severe PHPT. The postoperative course highlights the challenges in managing HBS, hypoparathyroidism, and long-term surveillance.
Adolescent ; Humans ; Parathyroid Neoplasms

Introduction: Incidental hyperparathyroidism with hypercalcemia is not uncommon. However, parathyroid carcinoma is an extremely rare endocrine malignancy, accounting for less than 1% of cases of primary hyperparathyroidism. Case: A 57-year-old Malay female with well-controlled type 2 diabetes was incidentally found to have hypercalcemia during hospitalization for pyelonephritis. She was asymptomatic, with no history of calcium supplementation or family history of endocrine disorders. Physical examination revealed no obvious neck swelling, and other systemic examinations were unremarkable. Investigations showed elevated serum calcium (2.87–3.4 mmol/L), low phosphate (0.34–0.76 mmol/L), and elevated intact parathyroid hormone (iPTH) (6.81 pmol/L). Her 25-OH vitamin D was deficient (45.58 nmol/L). Ultrasound of the neck revealed a solid lesion (1.6 × 2.0 × 2.8 cm) posterior to the right thyroid lobe with bilateral thyroid nodules, with the highest TR4, and normal cervical lymph nodes. Sestamibi scan showed multinodular goiter with cold nodules in bilateral thyroid lobes and a soft tissue lesion posterior to the right thyroid lobe. Subsequently, she underwent right hemithyroidectomy with intraoperative nerve monitoring and right inferior parathyroidectomy with intraoperative iPTH monitoring; the intraoperative iPTH level dropped appropriately from 24 to 2.4 pmol/L. Histopathological examination of the excised right parathyroid gland revealed parathyroid carcinoma, while the right thyroid lobe showed nodular hyperplasia. Postoperatively, calcium and iPTH levels normalized, and she remained well under follow-up. Conclusion Parathyroid carcinoma typically presents with markedly elevated calcium and iPTH levels, often alongside a palpable neck mass. However, in this patient, serum iPTH was only slightly above the upper limit of normal, with tumor size less than 3 cm, no lymph node or surrounding structures involvement from pre-operative evaluation imaging. This highlights the variability in both physical and biochemical presentations of parathyroid carcinoma and the challenges in distinguishing it from benign parathyroid tumors preoperatively.
Parathyroid Neoplasms

Introduction: Atypical parathyroid adenoma (APA) constitutes approximately 0.5–4.0% of all cases of primary hyperparathyroidism (pHPT). Here, we report a case of APA presenting with severe hypercalcemia, complicated with renal impairment, bilateral medullary nephrocalcinosis, and multiple fragility fractures. Case: A 45-year-old male initially presented with a 6-month history of constipation, polyuria, lethargy, bone pain, and difficulty in initiating micturition. Laboratory investigations revealed impaired renal function with an estimated glomerular filtration rate of 41.4 mL/min, severe hypercalcemia (4.07 mmol/L), and an elevated intact parathyroid hormone (iPTH) level of 104.0 pmol/L (reference range: 1.58–6.03 pmol/L), confirming the diagnosis of pHPT. He was also found to have vitamin D deficiency, with a serum total 25-hydroxyvitamin D level of 46 nmol/L. Ultrasound of the abdomen demonstrated bilateral medullary nephrocalcinosis, while neck ultrasound and Tc-99 m sestamibi parathyroid scintigraphy revealed a concordant lesion in the posterior aspect of the left thyroid lobe, suggestive of a parathyroid adenoma. He returned 3 months later with closed fractures of the right subtrochanteric femur and the right humerus following a fall from standing height. In view of persistent hypercalcemia despite hyperhydration and treatment with zoledronic acid, subcutaneous denosumab (60 mg) was administered, resulting in an improvement in serum calcium levels. A left inferior parathyroidectomy was then performed concurrently with internal fixation of the right femur. The surgery was uneventful. Histopathological examination confirmed an atypical parathyroid adenoma. Postoperatively, the serum calcium and iPTH levels normalized, and the patient remained asymptomatic and normocalcemic during regular follow-up. Conclusion APA remains a diagnostic and therapeutic challenge due to its clinical, biochemical, and histopathological features of equivocal malignancy. Surgical resection remains the mainstay of management of APA, and long-term surveillance is essential in view of its uncertain malignant potential and risk of recurrence.
Hypercalcemia ; 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.