Differential Diagnosis for Hypercalcemia and Elevated Alkaline Phosphatase
Single Most Likely Diagnosis
- Primary Hyperparathyroidism: This condition is the most common cause of hypercalcemia in outpatients, resulting from excessive parathyroid hormone (PTH) production, which leads to increased calcium levels and bone turnover, thus elevating alkaline phosphatase.
Other Likely Diagnoses
- Vitamin D Intoxication: Excessive intake of vitamin D can lead to increased absorption of calcium from the gut, causing hypercalcemia. Elevated alkaline phosphatase can occur due to the increased bone turnover.
- Malignancy-Associated Hypercalcemia: Certain cancers, such as breast, lung, and multiple myeloma, can produce substances that mimic the action of PTH or directly cause bone destruction, leading to hypercalcemia and elevated alkaline phosphatase.
- Paget's Disease of Bone: A condition characterized by excessive bone breakdown and formation, leading to elevated alkaline phosphatase and potential hypercalcemia, especially if there is significant bone resorption.
Do Not Miss Diagnoses
- Hypercalcemia of Malignancy with PTHrP (Parathyroid Hormone-related Protein): Although less common, certain malignancies can produce PTHrP, leading to severe hypercalcemia and elevated alkaline phosphatase. Missing this diagnosis could lead to delayed treatment of the underlying cancer.
- Familial Hypocalciuric Hypercalcemia (FHH): A rare genetic disorder that can mimic primary hyperparathyroidism but has different management implications. It's crucial to distinguish FHH from primary hyperparathyroidism to avoid unnecessary surgery.
Rare Diagnoses
- Sarcoidosis: A systemic granulomatous disease that can cause hypercalcemia due to increased vitamin D production by macrophages within granulomas. Alkaline phosphatase can be elevated, especially if there is liver or bone involvement.
- Thyroidosis: Hyperthyroidism can lead to increased bone turnover, resulting in elevated alkaline phosphatase and potential hypercalcemia, although this is less common.
- Immobilization Hypercalcemia: Prolonged immobilization, especially in young individuals with high bone turnover, can lead to hypercalcemia. Alkaline phosphatase may be elevated due to increased bone resorption.