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

Most Common Cause of Hypercalcemia in Hospitalized Patients

Metastatic carcinoma (option B) is the most common cause of hypercalcemia in hospitalized patients.

Epidemiology and Etiology

Hypercalcemia affects approximately 1% of the worldwide population 1, but the distribution of causes differs significantly between outpatient and inpatient settings:

• In hospitalized patients, malignancy is the predominant cause of hypercalcemia
• In the ambulatory general medical population, primary hyperparathyroidism is the most common cause 2

The evidence clearly shows that while primary hyperparathyroidism is the most common cause of hypercalcemia in outpatient settings, malignancy (metastatic carcinoma) is the most common cause in hospitalized patients 3, 2.

Mechanisms of Hypercalcemia in Malignancy

Malignancy-related hypercalcemia occurs through several mechanisms:

• Parathyroid hormone-related protein (PTHrP) production (most common)
• Increased active metabolite of vitamin D (calcitriol)
• Direct osteolytic hypercalcemia from bone metastases 4

PTHrP-mediated hypercalcemia is characterized by:

• Suppressed intact parathyroid hormone (iPTH) level
• Low or normal calcitriol level
• This contrasts with primary hyperparathyroidism, which shows elevated iPTH and calcitriol levels 4

Clinical Presentation

Hypercalcemia of malignancy typically presents with:

• Polyuria, polydipsia
• Nausea, confusion
• Vomiting, abdominal pain
• Myalgia
• Severe dehydration and acute renal failure in advanced cases
• Mental status changes, bradycardia, and hypotension when severe (>14.0 mg/dL) 4

Specific Cancer Associations

Hypercalcemia occurs in 10% to 25% of patients with lung cancer and is most commonly seen in patients with squamous cell lung cancer 4. Breast cancer has the highest prevalence of hypercalcemia among female malignancies, with approximately 10% of patients with bone metastases developing hypercalcemia at some point in their disease 5.

Prognosis

The prognosis for patients with hypercalcemia of malignancy is poor. The median survival after discovery of hypercalcemia of malignancy in patients with lung cancer is about 1 month 4, reflecting the advanced stage of disease typically associated with this complication.

Differential Diagnosis

While metastatic carcinoma is the most common cause of hypercalcemia in hospitalized patients, other causes to consider include:

1. Primary hyperparathyroidism (more common in outpatient settings)
2. Sarcoidosis and other granulomatous diseases
3. Immobility
4. Medication-induced hypercalcemia (thiazide diuretics, lithium)
5. Vitamin D intoxication

Management

Treatment of hypercalcemia of malignancy includes:

1. Rehydration with IV crystalloid fluids not containing calcium
2. Loop diuretics (after correction of intravascular volume)
3. Bisphosphonates (clodronate, pamidronate, and zoledronic acid)
4. Denosumab for refractory cases
5. Additional options: glucocorticoids, gallium nitrate, and salmon calcitonin 4

Bisphosphonates may efficiently control hypercalcemia, with calcium levels normalizing in 50% of patients treated with zoledronic acid compared with 33% in those treated with pamidronate by day 4 4.

In conclusion, while primary hyperparathyroidism is the most common cause of hypercalcemia in the general population, metastatic carcinoma is definitively the most common cause in hospitalized patients.