Hypercalcemia of Malignancy


Today we discussed an interesting case of acute encephalopathy due to hypercalcemia of malignancy due to bone metastases.

We first reviewed the importance of maintaining a broad differential for acute encephalopathy/delirium/acute confusional state/AMS.

We reviewed the following framework:

Neurologic / Toxic / Metabolic / Infectious / Other.

We then reviewed the differential for hypercalcemia. For those of you interested, please check out this awesome review video by Dr. Strong:

Our patient had hypercalcemia of malignancy and the following patients were made:

  • It is the most common cause of hypercalcemia in inpatients
  • The most commonly associated malignancies are breast, lung, multiple myeloma, and renal
  • There are three major mechanisms for hypercalcemia of malignancy
    • Secretion of PTHrP – 80% of malignancy related hyperCa
    • Osteolytic Metastases – ~20% of cases
    • Increased 1,25-OH-Vitamin D (calcitriol) 2/2 to increased 1-alpha-hydroxylase activity from activated macrophages in lymphomatous (and also granulomatous) tissue
  • We reviewed the PTH-based algorithm and determined that it was a PTH-independent process (PTH low or low-normal) and then used the PTHrP, calcidiol and calcitriol to guide to the correct diagnosis which was confirmed by MRI and bone scan

Finally, here is a way to distinguish between malignancy related hypercalcemia and primary hyperparathyroidism (most common cause in outpatients & higher co-occurrence in patients with malignancy)


For treatment options, please see the following blog post for more details!


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