Differential Diagnosis for Hypercalcemia with Hypercalciuria, Borderline Low Phosphate, Low Serum Osmolality, and Low Urine Osmolality

Single Most Likely Diagnosis

• Primary Hyperparathyroidism: This condition is characterized by the excessive production of parathyroid hormone (PTH), leading to hypercalcemia, hypercalciuria, and often, low serum phosphate levels due to increased renal phosphate excretion. The low serum and urine osmolality could be related to the effects of PTH on renal function and the resultant hypercalcemia-induced nephrogenic diabetes insipidus.

Other Likely Diagnoses

• Vitamin D Intoxication: Excessive intake of vitamin D can lead to increased absorption of calcium from the gut, resulting in hypercalcemia and hypercalciuria. Phosphate levels may be low due to the increased renal excretion of phosphate secondary to the hypercalcemia. Low serum and urine osmolality could be seen due to the effects of hypercalcemia on renal concentrating ability.
• Malignancy-Associated Hypercalcemia: Certain malignancies, such as squamous cell lung cancer, can produce parathyroid hormone-related protein (PTHrP), leading to hypercalcemia, hypercalciuria, and low phosphate levels. The low osmolality findings could be related to the systemic effects of the malignancy and hypercalcemia.

Do Not Miss Diagnoses

• Hypercalcemia of Malignancy with PTHrP: Similar to malignancy-associated hypercalcemia but emphasizes the importance of not missing a potentially life-threatening malignancy.
• Familial Hypocalciuric Hypercalcemia (FHH): A genetic disorder leading to hypercalcemia with relatively low urinary calcium excretion. However, in some cases, urinary calcium can be elevated, and the condition must be distinguished from primary hyperparathyroidism due to its different management approach.
• Lithium-Induced Hypercalcemia: Lithium therapy can lead to hyperparathyroidism or increased PTH secretion, resulting in hypercalcemia. It's crucial to identify this cause due to its implications for management, including potential adjustment of lithium therapy.

Rare Diagnoses

• Vitamin A Intoxication: Can lead to hypercalcemia due to increased bone resorption. While less common than vitamin D intoxication, it's a consideration in patients with excessive vitamin A intake.
• Thyroidosis with Hypercalcemia: Hyperthyroidism can cause hypercalcemia through increased bone turnover. Although less common, it's an important diagnosis to consider due to its distinct treatment approach.
• Williams Syndrome: A rare genetic disorder that can include hypercalcemia among its features, due to elastin gene deletion affecting calcium metabolism and renal function.