What is the most common cause of hypercalcemia in hospitalized patients?

Metastatic Carcinoma is the Most Common Cause of Hypercalcemia in Hospitalized Patients

The most common cause of hypercalcemia in hospitalized patients is metastatic carcinoma (option b). While primary hyperparathyroidism is the most common cause of hypercalcemia in the general population, malignancy becomes the predominant etiology in the hospital setting.

Epidemiology and Etiology

• In the ambulatory general medical population, primary hyperparathyroidism is the most common cause of hypercalcemia 1
• However, in hospitalized patients, malignancy is the most common cause of hypercalcemia 1, 2
• Cancer-related hypercalcemia occurs in approximately 20-30% of cancer patients at some point during their disease course 2
• Hypercalcemia of malignancy is associated with poor prognosis, reflecting advanced cancer stage 3

Mechanisms of Hypercalcemia in Malignancy

Malignancy causes hypercalcemia through several mechanisms:

1. Humoral hypercalcemia of malignancy (HHM): Tumors produce parathyroid hormone-related protein (PTHrP) that circulates systemically

   • Common in squamous cell cancers of lung, head and neck, and genitourinary tumors 4

2. Direct bone invasion: Tumor cells in bone produce local factors that stimulate osteoclastic bone resorption

   • Common in breast cancer and multiple myeloma 4

3. Combination mechanisms: Some tumors cause hypercalcemia through multiple pathways

Clinical Presentation

Hypercalcemia in hospitalized patients often presents with:

• Neurological symptoms: confusion, lethargy, somnolence, coma
• Gastrointestinal symptoms: nausea, vomiting, constipation
• Renal manifestations: polyuria, dehydration, decreased GFR
• Cardiac abnormalities: shortened QT interval, arrhythmias

Management of Hypercalcemia of Malignancy

Treatment approach for hypercalcemia in hospitalized patients:

1. Aggressive IV fluid resuscitation: Normal saline to correct dehydration and promote calciuresis 5
2. Bisphosphonates: First-line pharmacological treatment
   • Zoledronic acid 4 mg IV is preferred 5, 4
   • Pamidronate is an alternative option
3. Denosumab: For hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment 5
4. Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia 5
5. Glucocorticoids: Effective for hypercalcemia due to vitamin D toxicity, granulomatous disorders, or some lymphomas 5

Prognosis

• Hypercalcemia of malignancy indicates advanced disease with poor survival 6
• Median survival after discovery of hypercalcemia in lung cancer is approximately 1 month 5
• Treatment reduces serum calcium and improves symptoms, at least transiently 6

Other Causes of Hypercalcemia (Less Common in Hospitalized Patients)

• Primary hyperparathyroidism: Most common cause in outpatient setting
• Sarcoidosis and other granulomatous diseases: Through increased 1,25-dihydroxyvitamin D production
• Immobilization: Particularly in patients with high bone turnover
• Milk-alkali syndrome: From excessive intake of calcium and absorbable alkali
• Medication-induced: Thiazide diuretics, lithium, vitamin A or D toxicity

In summary, while primary hyperparathyroidism is the most common cause of hypercalcemia in the general population, metastatic carcinoma is the predominant cause in hospitalized patients, reflecting the advanced stage of disease that often necessitates hospitalization.