Differential Diagnosis for Hypercalcemia with Elevated 1,25 Dihydroxy Vitamin D

• Single Most Likely Diagnosis
  • Sarcoidosis: This condition is a common cause of hypercalcemia due to elevated 1,25 dihydroxy vitamin D levels. Sarcoidosis leads to an increased conversion of 25-hydroxy vitamin D to its active form, 1,25 dihydroxy vitamin D, by macrophages within granulomas, resulting in increased intestinal absorption of calcium and subsequent hypercalcemia.
• Other Likely Diagnoses
  • Lymphoma: Certain types of lymphoma can cause hypercalcemia through the production of 1,25 dihydroxy vitamin D by lymphoma cells, similar to sarcoidosis. This paraneoplastic syndrome leads to increased calcium absorption and hypercalcemia.
  • Tuberculosis: Like sarcoidosis, tuberculosis can cause an increase in 1,25 dihydroxy vitamin D levels due to granulomatous disease, leading to hypercalcemia.
• Do Not Miss Diagnoses
  • Vitamin D Intoxication: Although less common, vitamin D intoxication can lead to elevated levels of 1,25 dihydroxy vitamin D and severe hypercalcemia. It's crucial to distinguish between endogenous overproduction and exogenous overdose.
  • Primary Hyperparathyroidism with Co-existing Vitamin D Metabolism Disorder: While primary hyperparathyroidism typically causes hypercalcemia through parathyroid hormone (PTH) elevation, co-existing disorders affecting vitamin D metabolism could lead to elevated 1,25 dihydroxy vitamin D levels, complicating the diagnosis.
• Rare Diagnoses
  • Williams Syndrome: A rare genetic disorder that can lead to hypercalcemia due to elevated 1,25 dihydroxy vitamin D levels, among other symptoms.
  • Idiopathic Hypercalcemia of Infancy: A rare condition in infants characterized by hypercalcemia, which can be associated with elevated vitamin D levels, although the exact mechanism may vary and can include genetic predispositions affecting vitamin D metabolism.