# Severe Hypercalcemia and Confusion in a Middle‐Aged Male: The Hidden Diagnosis of Parathyroid Carcinoma

## TL;DR

A 53-year-old man with severe hypercalcemia and confusion was diagnosed with rare parathyroid cancer after surgery and lab tests revealed abnormal calcium and PTH levels.

## Contribution

This case highlights the diagnostic challenges and clinical features of parathyroid carcinoma, emphasizing the importance of preoperative suspicion.

## Key findings

- Severe hypercalcemia and elevated PTH levels were key indicators of parathyroid carcinoma.
- Histopathological confirmation after surgery confirmed the rare diagnosis of parathyroid cancer.
- Aggressive hydration and denosumab improved calcium levels and renal function in the patient.

## Abstract

Parathyroid cancer (PC) is one of the rarest causes of primary hyperparathyroidism (PHPT), typically exhibiting an indolent course but presenting with more severe symptoms compared to its benign counterparts. The diagnosis is most often made postoperatively through histopathological examination; however, certain clinical and biochemical features may raise suspicion preoperatively. These include markedly elevated serum calcium and parathyroid hormone (PTH) levels, a large parathyroid lesion with suspicious ultrasonographic features, and evidence of renal or skeletal complications. Although the exact etiology remains unclear, somatic mutations in the CDC73 gene have been identified in patients with PC. Complete surgical resection via en bloc excision remains the first‐line and most effective therapeutic approach to maximize the chance of cure, although recurrence is common during follow‐up. Other treatment modalities, including radiotherapy, chemotherapy, and immunotherapy, have limited evidence supporting their efficacy. Here, we report the case of a 53‐year‐old male who presented with lower limb weakness, confusion, and significant weight loss over the preceding month. His past medical history included prediabetes and dyslipidemia. Initially evaluated by a neurologist for depressive symptoms, he subsequently developed rapidly progressive neurocognitive decline, impaired mobility, and continued unexplained weight loss. Upon hospital admission, he was somnolent and confused, though hemodynamically stable. Laboratory investigations revealed severe hypercalcemia at 18 mg/dL (reference range: 8.5–10.5), acute kidney injury with a creatinine of 4.2 mg/dL (0.7–1.3), and a markedly elevated PTH level of 1095 pg/mL (10–65). Initial management included aggressive intravenous hydration and administration of denosumab to control the symptomatic hypercalcemia, which resulted in improved calcium levels and renal function. Further evaluation with imaging, including parathyroid ultrasound and Technetium‐99m (Tc‐99m) sestamibi scintigraphy, was consistent with a right parathyroid adenoma. The patient subsequently underwent parathyroidectomy, and histological analysis confirmed the diagnosis of parathyroid carcinoma.