Introduction: Severe hypercalcemia is most commonly caused by primary hyperparathyroidism (PHPT) and malignancy. While standard therapies are effective in most cases, a subset of patients have persistent or refractory hypercalcemia. We present a retrospective case series detailing the clinical characteristics, biochemistry, and outcomes of patients treated with denosumab for hypercalcemia. Cases: Seven patients with severe hypercalcemia were identified, comprising five with PHPT and two with malignancyassociated hypercalcemia. The mean age was 70.4 years (range 55–86), with 71% female (n = 5) and 29% male (n = 2). Baseline corrected calcium ranged from 2.92 to 4.59 mmol/L, with a mean of 3.26 mmol/L. In the PHPT cohort, parathyroid hormone (PTH) levels were significantly elevated (16.7–168 pmol/L), while malignancy patients had suppressed PTH (0.6 and 0.9 pmol/L). Prior to denosumab, 4/7 patients (57%) received bisphosphonates, 3/7 (43%) received calcitonin, and 1/7 (14%) was treated with cinacalcet. Denosumab resulted in a mean reduction in corrected calcium of 0.22 mmol/L from 3.26 to 3.03 mmol/L. Biochemical response was observed in 5/7 patients (71%). Of these, 3 patients (43%) achieved normocalcemia, while 2 patients (29%) demonstrated a partial response. The remaining 2/7 patients (29%) showed no significant improvement in calcium levels. Among responders, the mean time to calcium reduction to <3.0 mmol/L was 27 days (range 7–47). Repeat dosing was required in the majority of patients, with a mean of 1.7 doses per patient (range 1–4), indicating variability in both onset and durability of response. Among patients with PHPT, four underwent parathyroidectomy, and one declined surgery. Both patients with malignancy were managed nonsurgically. Conclusion Denosumab achieved normocalcemia in 43% of patients, with additional partial responses. Its effects were variable, with delayed response and frequent need for repeat dosing, supporting its role as an adjunctive or bridging therapy rather than as a definitive treatment.
Denosumab ; Hypercalcemia ; Retrospective Studies

Introduction: Severe hypercalcemia is a life-threatening metabolic emergency that necessitates prompt initiation of systemic therapy due to the risk of cardiac arrhythmias. It is frequently linked to squamous cell carcinoma through the production of parathyroid hormone–related protein, which mediates the development of humoral hypercalcemia of malignancy. Case: This is a case of a 38-year-old male who was diagnosed 1 year ago with locally advanced poorly differentiated basaloid squamous cell carcinoma of the lower anterior mandibular alveolus involving cortical, medullary bone, and perineural invasion. He underwent extensive tumor resection with reconstruction, tracheostomy, and bilateral neck dissection, followed by multiple revision surgeries for postoperative complications. He completed adjuvant chemoradiotherapy. He presented with acute confusion without other systemic symptoms. His Glasgow Coma Scale was E4V4M5. Neurological and systemic examinations were unremarkable, and oral cavity assessment showed no evidence of recurrence. Investigations revealed severe hypercalcemia (5.94 mmol/L) with normal phosphate (1.16 mmol/L) associated with shortened QTc. Other tests were unremarkable, with no evidence of infection, uremia, liver dysfunction, or alternative metabolic causes. Lumbar puncture was unremarkable. His parathyroid hormone level was suppressed at 0.50 pg/ mL. Computed tomography brain showed no evidence of meningoencephalitis, hydrocephalus, cerebral oedema, or metastasis. Aggressive hydration was initiated alongside subcutaneous calcitonin, which was subsequently titrated. However, there was no clinical or biochemical improvement after 1 day, with persistent confusion and calcium remaining at 5.87 mmol/L. Subcutaneous denosumab was then administered, and hemodialysis was initiated on alternate days due to refractory hypercalcemia. This resulted in improvement of calcium levels to 3.2–3.6 mmol/L and resolution of confusion Conclusion Refractory hypercalcemia may represent a late manifestation of advanced squamous cell carcinoma and is an ominous prognostic indicator, necessitating prompt evaluation and oncologic management.
Calcitonin ; Denosumab ; Hypercalcemia ; Renal Dialysis ; 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

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

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.
Humans ; Multiple Myeloma/drug therapy* ; Bortezomib/therapeutic use* ; Hypercalcemia ; Prognosis ; Chromosome Aberrations ; Kidney/physiology* ; Renal Insufficiency, Chronic ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols

Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.
Hyperparathyroidism ; Reoperation ; Hypercalcemia

To review the diagnosis and treatment of a case of hypercalcium crisis caused by primary hyperparathyroidism（PHPT） and prophylactic treatment of hungry bone syndrome. In a 32-year-old male with hypercalcemia, the main manifestations were loss of appetite, nausea, polyuria, polydipsia, fatigue, lethargy, etc. parathyroid hormone, serum calcium increased, thyroid function was normal, thyroid color ultrasound and MRI showed space-occupying behind the right thyroid, radionuclide examination showed abnormal imaging agent concentration in the right parathyroid area, there was a history of pathological fracture. Clinically diagnosed as hypercalcemia crisis secondary to PHPT.
Male ; Humans ; Adult ; Hypercalcemia/diagnosis* ; Hyperparathyroidism, Primary/surgery* ; Parathyroid Hormone ; Hypocalcemia/complications* ; Thyroid Gland ; Calcium

Primary hyperparathyroidism (PHPT) is a common endocrine condition, increasingly presenting asymptomatically and detected on routine laboratory examination in developed countries. Multiple spontaneous tendon ruptures as the initial presentation of PHPT is extremely rare. We present the case of a 28-year-old male diagnosed with severe hypercalcemia secondary to PHPT after presenting with complications of multiple spontaneous tendon ruptures,and discuss the management issues in PHPT for this patient.
Hyperparathyroidism, Primary ; Hypercalcemia

Eight cases of parathyroid carcinoma were identified (8 females; median age 45 years, range 28-72). Half of whom were diagnosed preoperatively. Hypercalcemic symptoms were seen in 87.5% of the patients and the main complication was nephrolithiasis. At presentation, the median calcium was 3.675 mmol/L, median phosphate of 0.68 mmol/L, median intact parathyroid hormone (iPTH) was 211 pmol/L. Five patients had regional nodes metastasis and 1 had distant metastasis to the lungs. Parathyroid gland invasion to adjacent structures was seen in 62.5% of cases while another 62.5% showed capsular or vascular infiltration on histology with median tumour size of 3.2 cm. Recurrent hypercalcemia occurred in 50% of the patients with median time of recurrence of 21 months. In this case series, we found that patients with severe hypercalcemia and high iPTH also exhibited a high index suspicion of PC.
Parathyroid Neoplasms ; Carcinoma ; Hypercalcemia

BACKGROUND: Hypercalcemia is an important metabolic emergency condition in cancer patients. Bisphosphonate is the treatment of choice for hypercalcemia, whereas calcitonin and hydration with furosemide are recommended for acute supportive therapy. However, data regarding real-world treatment patterns and outcomes of pharmacological treatments are limited. Therefore, we aimed to investigate the treatment patterns and clinical outcomes of hypercalcemia treatment in solid tumor patients. METHODS: Electronic medical records of 123 adults with solid cancers and albumin-corrected calcium levels >10.5 mg/dL or ionized calcium levels >1.35 mmol/L were reviewed. We retrospectively analyzed the pharmacological treatment and recovery rate according to the severity of hypercalcemia. RESULTS: A total of 177 cases were identified, of which 49 were not treated and 30 were treated with hydration only. In moderate-to-severe cases, 86.5% received pharmacological treatment. Thirty-four cases (19.2%) were treated with bisphosphonate alone and 58 cases (32.8%) were treated with bisphosphonate and calcitonin. In mild hypercalcemia cases, the recovery rate was higher for those receiving hydration only or pharmacological treatment (79.7%) than for those receiving no treatment (61.4%, p = 0.041). Most moderate-to-severe cases were treated with medication and of those treated, 56.3% recovered. The recovery rate was lower in those treated with bisphosphonate alone (38.2%) than in those who underwent calcitonin combination treatment (73.7%, p = 0.001). CONCLUSIONS: Bisphosphonate combined with calcitonin was found to be more effective than bisphosphonate alone for the treatment of moderate-to-severe hypercalcemia. Considering the current shortage of calcitonin, further efforts are required to ensure its stable supply.
Adult ; Calcitonin ; Calcium ; Electronic Health Records ; Emergencies ; Furosemide ; Humans ; Hypercalcemia ; Retrospective Studies