Differential Diagnosis for Hypercalcemia

The following is a differential diagnosis for hypercalcemia, categorized for clarity and emphasis on critical conditions.

• Single Most Likely Diagnosis

  • Primary hyperparathyroidism: This is the most common cause of hypercalcemia in outpatient settings, often due to a parathyroid adenoma or hyperplasia, leading to excessive parathyroid hormone (PTH) production and subsequent hypercalcemia.

• Other Likely Diagnoses

  • Malignancy-associated hypercalcemia: Various cancers, such as breast, lung, and multiple myeloma, can cause hypercalcemia through the production of parathyroid hormone-related protein (PTHrP) or by bone metastasis.
  • Vitamin D intoxication: Excessive intake of vitamin D can lead to hypercalcemia due to increased absorption of calcium from the gut.
  • Familial hypocalciuric hypercalcemia (FHH): A genetic disorder characterized by hypercalcemia, low urinary calcium excretion, and often, a family history of the condition.

• Do Not Miss Diagnoses

  • Hypercalcemia of malignancy with parathyroid hormone-related protein (PTHrP): Although included under malignancy, it's crucial to identify this specific mechanism due to its implications for treatment and prognosis.
  • Multiple myeloma: Given its potential for severe and rapid progression, early diagnosis is critical.
  • Pheochromocytoma: Though rare, pheochromocytomas can produce PTHrP, leading to hypercalcemia, and missing this diagnosis could have fatal consequences due to the potential for hypertensive crises.

• Rare Diagnoses

  • Sarcoidosis: A condition where granulomatous disease leads to increased conversion of vitamin D to its active form, resulting in hypercalcemia.
  • Thyrotoxicosis: Hyperthyroidism can cause hypercalcemia, possibly due to increased bone turnover.
  • Adrenal insufficiency: Rarely, Addison's disease can present with hypercalcemia, possibly due to increased bone resorption or hemoconcentration.
  • Milk-alkali syndrome: Characterized by hypercalcemia, metabolic alkalosis, and renal impairment, typically resulting from excessive intake of calcium and absorbable alkali.
  • Immobilization hypercalcemia: Seen in patients with high bone turnover rates (e.g., those with Paget's disease or extensive bone metastases) who become immobilized, leading to an imbalance in bone resorption and formation.