Differential Diagnosis for Hypercalcemia

The differential diagnosis for hypercalcemia can be organized into the following categories:

• Single Most Likely Diagnosis
  • Primary hyperparathyroidism: This is the most common cause of hypercalcemia, accounting for approximately 80% of cases. It is characterized by an overproduction of parathyroid hormone (PTH), leading to increased calcium levels in the blood. Justification: High prevalence and well-established pathophysiology.
• Other Likely Diagnoses
  • Malignancy-associated hypercalcemia: Various types of cancer, such as breast, lung, and multiple myeloma, can cause hypercalcemia through the production of parathyroid hormone-related protein (PTHrP) or other mechanisms. Justification: Common comorbid condition with a well-understood mechanism.
  • Vitamin D intoxication: Excessive intake of vitamin D can lead to hypercalcemia due to increased absorption of calcium from the gut. Justification: Recognizable pattern of excessive supplementation.
  • Familial hypocalciuric hypercalcemia (FHH): A rare genetic disorder characterized by an inactivating mutation in the calcium-sensing receptor, leading to hypercalcemia. Justification: Distinctive family history and mild hypercalcemia.
• Do Not Miss Diagnoses
  • Hypercalcemia of malignancy with parathyroid hormone-related protein (PTHrP): Some cancers, like squamous cell lung carcinoma, can produce PTHrP, leading to severe hypercalcemia. Justification: Potentially life-threatening if not promptly addressed.
  • Multiple myeloma: A type of blood cancer that can cause hypercalcemia through various mechanisms, including bone destruction and production of osteoclast-activating factors. Justification: Serious underlying condition requiring prompt diagnosis and treatment.
  • Vitamin A intoxication: Excessive intake of vitamin A can cause hypercalcemia, although this is less common than vitamin D intoxication. Justification: Potential for severe toxicity if not recognized.
• Rare Diagnoses
  • Sarcoidosis: A systemic granulomatous disease that can cause hypercalcemia due to increased production of 1,25-dihydroxyvitamin D. Justification: Uncommon presentation, but recognizable pattern of systemic symptoms.
  • Thyrotoxicosis: Severe hyperthyroidism can lead to hypercalcemia, although this is a rare cause. Justification: Distinctive clinical features and laboratory findings.
  • Pheochromocytoma: A rare tumor of the adrenal gland that can produce PTHrP, leading to hypercalcemia. Justification: Uncommon presentation, but potentially life-threatening if not diagnosed.
  • Immobilization hypercalcemia: Prolonged immobilization, especially in young individuals with high bone turnover, can cause hypercalcemia. Justification: Recognizable clinical context and reversible condition.