Differential Diagnosis for Hypercalcemia in MS. Shanna Seebachan
Single Most Likely Diagnosis
- Primary Hyperparathyroidism: Given the patient's high calcium levels that improved with IV fluids but then rose again, and a PTH level of 13, which is elevated, primary hyperparathyroidism is a strong consideration. The PTH level, although not very high, is inappropriately normal given the high calcium levels, suggesting that the parathyroid glands are not suppressing PTH secretion as they should in the face of hypercalcemia.
Other Likely Diagnoses
- Vitamin D Toxicity or Excess: Although the Vitamin 25 OH level is 75.4, which is within the normal to high range, and the 1,25 OH vitamin D level is pending, excessive levels of vitamin D can lead to hypercalcemia. The fact that the patient's calcium improved with IV fluids but then increased again suggests an ongoing process that could be related to vitamin D metabolism.
- Malignancy: Hypercalcemia of malignancy can be due to various types of cancer, including those that produce PTH-related protein (PTHrP). Although the patient's CT scans were unremarkable, malignancy can sometimes be occult, and further investigation might be needed, especially if other symptoms or signs develop.
Do Not Miss Diagnoses
- Multiple Myeloma: This is a plasma cell dyscrasia that can cause hypercalcemia through the production of osteoclast-activating factors. It's crucial not to miss this diagnosis because it requires specific treatment. The patient's anemia (Hgb 10.2 -> 9.8) could be a clue, as anemia is a common feature of multiple myeloma.
- Hypercalcemia of Malignancy with PTHrP: Similar to multiple myeloma, other malignancies can produce substances that mimic the action of PTH, leading to hypercalcemia. Missing this diagnosis could delay the treatment of an underlying cancer.
Rare Diagnoses
- Familial Hypocalciuric Hypercalcemia (FHH): This is a rare genetic disorder characterized by hypercalcemia with low urinary calcium excretion. It's usually benign but can be confused with primary hyperparathyroidism. Genetic testing might be necessary if other causes are ruled out.
- Granulomatous Diseases (e.g., Sarcoidosis): These conditions can cause hypercalcemia due to increased conversion of vitamin D to its active form by macrophages within granulomas. Although less likely given the lack of other symptoms or findings suggestive of granulomatous disease, it remains a consideration, especially if other tests are negative.
Management should include further diagnostic workup to confirm the diagnosis, such as:
- Completing the vitamin D workup (1,25 OH vitamin D level)
- Evaluating for malignancy (e.g., bone marrow biopsy if multiple myeloma is suspected, or imaging studies for other cancers)
- Considering a parathyroid scan or biopsy if primary hyperparathyroidism is highly suspected
- Monitoring calcium and PTH levels
- Managing hypercalcemia symptoms and preventing complications.