What causes elevated calcium levels in pancreatitis?

Calcium Elevation in Pancreatitis: Mechanisms and Implications

In pancreatitis, calcium levels are typically decreased rather than elevated due to free fatty acids binding to calcium and forming insoluble calcium soaps in areas of fat necrosis. This process, known as saponification, leads to hypocalcemia, which is a frequent finding in acute pancreatitis and is considered a negative prognostic factor when levels fall below 2 mmol/L 1.

Mechanisms of Calcium Changes in Pancreatitis

• In acute pancreatitis, circulating lipase and phospholipase released during pancreatic inflammation cleave triglycerides and raise serum free fatty acids (FFA) 1
• These free fatty acids may lead to intravascular sequestration of calcium by creating FFA-albumin complexes, resulting in hypocalcemia 1
• Hypocalcemia is frequently observed in patients with acute pancreatitis, with calcium levels below 2 mmol/L being a well-known negative prognostic factor 1

When Calcium is Elevated in Pancreatitis

While hypocalcemia is the typical finding, elevated calcium can occasionally be seen in pancreatitis due to:

1. Primary Hyperparathyroidism

• Hypercalcemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5-8% 2
• The pathophysiological mechanism involves elevated parathyroid hormone and high serum calcium levels, which may lead to calcium deposits in pancreatic ducts and activation of pancreatic enzymes 2
• Pancreatitis associated with hyperparathyroidism tends to be severe and may lead to complications such as pseudocysts and pancreatic necrosis 2

2. Secondary Hyperparathyroidism

• Patients with chronic renal insufficiency have a higher risk of secondary hyperparathyroidism, which can lead to hypercalcemia and recurrent episodes of acute pancreatitis 3
• This is particularly relevant in patients on regular hemodialysis programs 3

3. Calcitonin Response

• During the acute phase of pancreatitis, serum calcitonin levels are usually elevated as a physiological response to regulate calcium levels 4
• In a study of 29 patients with acute pancreatitis, 22 had elevated calcitonin values during the acute phase of the disease 4

Clinical Implications

• In cases of recurrent pancreatitis without obvious etiology, hyperparathyroidism should be considered even if significant elevation of serum calcium is not initially present 3
• Serum calcium should be measured in all patients with acute pancreatitis, especially in cases of recurrent episodes 5
• The diagnosis of hyperparathyroidism as a cause of pancreatitis is frequently overlooked or delayed as symptoms are non-specific and serum calcium is not routinely measured in acute pancreatitis 5

Diagnostic Approach

• In the absence of gallstones or significant history of alcohol use, serum calcium levels should be measured 1
• If hypercalcemia is detected, further workup for hyperparathyroidism is warranted, including measurement of parathyroid hormone levels 5
• Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi should be performed to confirm clinical suspicion of parathyroid adenoma 2

Treatment Considerations

• Surgical resection (parathyroidectomy) is the definitive treatment for pancreatitis caused by hyperparathyroidism with excellent results 2
• Early diagnosis and treatment of hyperparathyroidism may reduce the chances of complications and recurrent episodes of pancreatitis 5

In summary, while hypocalcemia is the typical finding in acute pancreatitis due to calcium sequestration by free fatty acids, elevated calcium levels may indicate underlying hyperparathyroidism, which should prompt appropriate diagnostic workup and targeted treatment.