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: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence even after surgical resection. Surgery remains the mainstay of treatment, while adjuvant options are limited. Mitotane is the only approved systemic therapy. Current guidelines recommend stereotactic body radiotherapy (SBRT) alongside adjuvant mitotane therapy in Rx, R1, R2 resections and in locally advanced disease. Case: We present a case of a 40-year-old female who presented with abdominal pain and was found to have a large heterogeneous left adrenal mass measuring 8.2 × 8.5 × 9.5 cm (Hounsfield Unit 63) on computed tomography (CT) imaging. Clinically, she was obese with a body mass index of 33.7 kg/m². No discriminatory feature of Cushing’s was present. Hormonal evaluation demonstrated autonomous cortisol secretion with failure of suppression on both overnight and low-dose dexamethasone suppression tests at 301 nmol/L and 313.6 nmol/L, respectively. DHEA, testosterone, and urinary metanephrine were within range. Hemoglobin A1c was 6.6%. She underwent open left adrenalectomy. Intra-operatively, a 12 × 10 cm adrenal tumor was identified with multiple areas of tumor rupture and spillage during mobilization. HPE confirmed high-grade ACC with high Weiss score of 8, Ki-67 index 60–80%, and mitotic count 54/50 hpf (pT2Nx). Post-operative CT imaging demonstrated a residual soft tissue lesion in the left adrenal bed (largest diameter 3.8 cm) with fluorodeoxyglucose avidity. We commenced adjuvant mitotane therapy, titrated to 2 g TDS with supraphysiological hydrocortisone replacement. Mitotane level was within therapeutic range (16 mcg/mL). She was deemed unsuitable for repeat surgery due to the proximity of the residual mass to the adjacent vessel and was planned for SBRT therapy after a multidisciplinary team discussion. Conclusion High-risk ACC with suspected residual disease remains a therapeutic challenge. While mitotane remains the cornerstone of adjuvant therapy, SBRT may represent a promising adjunctive local treatment modality in carefully selected patients. Further studies are required to define its role in improving local control and outcomes in ACC.
Adrenocortical Carcinoma ; Mitotane

Introduction: Cushing’s syndrome is a multisystem disorder with significant cardiovascular morbidity, yet presentation as acute heart failure is uncommon. When driven by adrenocortical carcinoma (ACC), the clinical course is often aggressive and rapidly fatal, with particularly poor out-comes in resourcelimited settings where access to therapy is constrained. Case: A 39-year-old previously well female presented with acute decompensated heart failure, newly diagnosed hypertension, type 2 diabetes mellitus, and obesity, preceded by a 3-year history of secondary amenorrhea and progressive weight gain. On admission, she exhibited florid Cushingoid features. Biochemical evaluation confirmed severe adrenocorticotropic hormone (ACTH)-independent hypercortisolism: morning serum cortisol 1,950 nmol/L, failure of suppression on overnight dexamethasone suppression test (post-ODST cortisol 2022.9 nmol/L), and elevated 24-hour urinary free cortisol (2,069 nmol/24 hours, 2.56 × upper limit of normal). Androgen excess was evident, with elevated dehydroepiandrosterone sulfate (DHEAS more than 27 µmol/L) and testosterone (9.91 nmol/L). ACTH was suppressed, supporting an adrenal source, while aldosterone was normal. Contrast-enhanced computed tomography demonstrated a large left adrenal mass (12 cm) with tumor thrombus extending into the inferior vena cava and renal veins, with extensive hepatic and pulmonary metastases, consistent with advanced ACC. Management was limited by disease severity and resource constraints. Ketoconazole was contraindicated due to transaminitis, and alternative steroidogenesis inhibitors were unavailable, leaving metyrapone as the only feasible option. Oncological therapy was deferred due to sepsis and clinical instability. Her course was fulminant, complicated by recurrent heart failure, sepsis, and metabolic derangements, culminating in refractory cardiopulmonary failure. She died within 1 month of diagnosis, prior to definitive oncological intervention. Conclusion Fulminant cortisol-secreting ACC may present catastrophically as acute heart failure and progress rapidly. Early recognition and timely access to multimodal cortisollowering therapy are critical, particularly in resourcelimited settings. In fulminant hypercortisolism, the challenge is not diagnosis—but timing.
Adrenocortical Carcinoma ; Hydrocortisone ; Heart Failure

Introduction: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a predilection for metastasis to the liver, lungs, and lymph nodes. Bone involvement is less common and typically occurs alongside widespread disease. Isolated skeletal progression without visceral involvement is unusual and not well characterized. Case: A 60-year-old female underwent left adrenalectomy in 2019 for an incidentally detected adrenal mass, which was reported as a benign adrenal cortical adenoma (Ki67 <3%). In 2022, she presented with persistent low back pain. Imaging demonstrated fluorodeoxyglucoseavid lesions involving the T12 vertebra and right ilium, without evidence of local recurrence or visceral metastases. Histopathological evaluation of a bone biopsy initially suggested a neuroendocrine neoplasm based on synaptophysin positivity. Following multiple expert reviews and integration of clinical, radiological, and immunohistochemical findings, a consensus diagnosis of metastatic ACC was established. She received palliative radiotherapy to symptomatic skeletal sites and subsequently completed six cycles of etoposide, doxorubicin, and cisplatin chemotherapy in 2023, achieving disease stabilization. Surveillance imaging in May 2025 demonstrated progression confined to the axial and appendicular skeleton, with no involvement of the adrenal bed or visceral organs. Mitotane therapy was initiated in December 2025. Ongoing management focuses on systemic disease control, symptom palliation, and multidisciplinary supportive care. Conclusion This case illustrates an uncommon pattern of ACC progression characterized by bone-dominant metastases in the absence of visceral disease. It also highlights the importance of reconsidering the initial histopathological diagnosis when clinical behavior is discordant. Vigilance for atypical metastatic patterns is warranted, even years after resection of an adrenal lesion initially classified as benign.
Adrenocortical Carcinoma

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