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.

Human ; Parathyroid Neoplasms ; Hyperparathyroidism ; Fractures, Spontaneous ; Philippines

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

OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Primary hyperparathyroidism is characterized by increased secretion of parathyroid hormone, leading to hypercalcemia and skeletal and renal complications. In the past, it was diagnosed when presenting with classical signs and symptoms. Currently, the most common clinical presentation of PHPT is asymptomatic hypercalcemia, often detected by routine screening tests. Due to the changing presentations, the diagnosis can become challenging.

We present BA, a 16-year-old female with a 2-year history of multiple fractures, progressive lytic bone lesions and pain, and kidney stones. She was initially managed as a case of polyostotic fibrous dysplasia. The workup also revealed low levels of vitamin D, hypercalcemia, increased alkaline phosphatase, and elevated intact parathyroid hormones. A neck ultrasound revealed two solid masses posterior to the right thyroid lobe.

She underwent right parathyroidectomy, and a biopsy confirmed a double parathyroid adenoma.

This report also highlights the management of the case in a low-resource setting and the importance of timely diagnosis of primary hyperthyroidism to prevent a delay in the management, which could cause unnecessary pain, bone deformities, and disability.

Human ; Female ; Adolescent: 13-18 Yrs Old ; Parathyroid Hormone ; Parathyroid Neoplasms ; Parathyroidectomy ; Phosphoric Monoester Hydrolases ; Fractures, Multiple ; Hypercalcemia ; Hyperparathyroidism ; Hyperthyroidism

The parathyroid glands play a crucial role in calcium regulation through parathyroid hormone (PTH) production. Indicators for those with hyperparathyroidism would be elevated serum calcium and PTH levels with further evaluation followed by imaging with neck ultrasonography and parathyroid scintigraphy. Limitations in the initial imaging modalities include operator-dependent sensitivity in neck ultrasonography, and poor spatial resolution, and poor sensitivity for smaller-sized adenomas in parathyroid scintigraphy.

This case report describes a 24-year-old female with elevated parathyroid hormone, and borderline elevated calcium levels with an initial diagnosis of primary hyperparathyroidism secondary to a suspected parathyroid adenoma. The dual tracer dual-phase scintigraphy accompanied by SPECT/CT and subtraction method was negative for a parathyroid adenoma, however, ultrasonography of the neck showed a suspicious nodular structure. Due to the high clinical suspicion, a subsequent ¹⁸F-Choline PET/CT was done and identified an ¹⁸F-Choline-avid lesion, highly suggestive of a parathyroid adenoma. This prompted parathyroidectomy in which histopathology as well as intraoperative reduction in parathyroid hormone levels, confirmed the presence of a parathyroid adenoma.

This is the first recorded ¹⁸F-Choline PET/CT usage for a parathyroid adenoma in the country and highlights the potential of its usage as a sensitive and specific imaging modality in cases where conventional imaging is inconclusive.

Human ; Female ; Young Adult: 19-24 Yrs Old ; Parathyroid Adenoma ; Parathyroid Neoplasms ; Hyperparathyroidism

: The parathyroid glands play a crucial role in calcium regulation through parathyroid hormone (PTH) production. Indicators for those with hyperparathyroidism would be elevated serum calcium and PTH levels with further evaluation followed by imaging with neck ultrasonography and parathyroid scintigraphy. Limitations in the initial imaging modalities include operator-dependent sensitivity in neck ultrasonography, and poor spatial resolution, and poor sensitivity for smaller-sized adenomas in parathyroid scintigraphy. : This case report describes a 24-year-old female with elevated parathyroid hormone, and borderline elevated calcium levels with an initial diagnosis of primary hyperparathyroidism secondary to a suspected parathyroid adenoma. The dual tracer dual-phase scintigraphy accompanied by SPECT/CT and subtraction method was negative for a parathyroid adenoma, however, ultrasonography of the neck showed a suspicious nodular structure. Due to the high clinical suspicion, a subsequent 18F-Choline PET/CT was done and identified an 18F-Choline-avid lesion, highly suggestive of a parathyroid adenoma. This prompted parathyroidectomy in which histopathology as well as intraoperative reduction in parathyroid hormone levels, confirmed the presence of a parathyroid adenoma. This is the first recorded 18F-Choline PET/CT usage for a parathyroid adenoma in the country and highlights the potential of its usage as a sensitive and specific imaging modality in cases where conventional imaging is inconclusive.
Human ; Female ; Young Adult: 19-24 yrs old ; parathyroid adenoma ; parathyroid neoplasms ; hyperparathyroidism