Differential Diagnosis for Hypercalcemia with Hypophosphatemia and Low PTH

Single Most Likely Diagnosis

• Vitamin D intoxication: This condition leads to increased absorption of calcium from the gut, resulting in hypercalcemia, and also causes hypophosphatemia due to increased phosphate excretion in the urine. The PTH level is low because the high calcium levels feedback inhibit PTH secretion.

Other Likely Diagnoses

• Malignancy-associated hypercalcemia (e.g., multiple myeloma, lymphoma): Certain malignancies can produce PTH-related protein (PTHrP), which mimics the action of PTH, leading to hypercalcemia and hypophosphatemia. However, the actual PTH level is low due to feedback inhibition.
• Familial hypocalciuric hypercalcemia (FHH): Although PTH levels might be in the normal or slightly elevated range, in the context of very low urinary calcium excretion, a low PTH level in the setting of hypercalcemia could be considered. This is a genetic disorder affecting the calcium-sensing receptor, leading to inappropriate PTH secretion for the level of calcium.
• Hyperthyroidism: Thyrotoxicosis can cause hypercalcemia due to increased bone resorption. Phosphate levels can be low due to increased renal excretion. PTH levels are typically low due to the direct effect of thyroid hormones on bone and the kidney.

Do Not Miss Diagnoses

• Primary adrenal insufficiency (Addison's disease): Hypercalcemia can occur due to increased renal reabsorption of calcium and decreased excretion. Hypophosphatemia might not be a primary feature but can occur. PTH levels are low, partly due to the lack of the adrenal hormones' influence on calcium and phosphate metabolism.
• Pheochromocytoma: Rarely, pheochromocytomas can produce PTHrP, leading to hypercalcemia and hypophosphatemia with low PTH levels.

Rare Diagnoses

• Vitamin A intoxication: Can cause hypercalcemia due to increased bone resorption. Phosphate levels might be low, and PTH levels are typically low due to feedback inhibition.
• Sarcoidosis: Although more commonly associated with elevated 1,25-dihydroxyvitamin D and hypercalcemia, in rare cases, PTH levels might be low, especially if the disease process leads to significant hypercalcemia and subsequent feedback inhibition of PTH secretion.
• Immobilization hypercalcemia: Typically seen in young individuals with high bone turnover (e.g., those with spinal cord injuries), it can lead to hypercalcemia and hypophosphatemia with low PTH levels due to the immobilization-induced increase in bone resorption.