Differential Diagnosis for Elevated Calcium with Normal Intact PTH
Single Most Likely Diagnosis
- Malignancy-associated hypercalcemia: This is often due to the production of parathyroid hormone-related protein (PTHrP) by tumor cells, leading to elevated calcium levels without an increase in intact PTH. Common malignancies associated with this condition include squamous cell lung cancer, breast cancer, and multiple myeloma.
Other Likely Diagnoses
- Vitamin D intoxication: Excessive intake of vitamin D can lead to increased absorption of calcium from the gut, resulting in hypercalcemia. This condition can occur with normal intact PTH levels.
- Familial hypocalciuric hypercalcemia (FHH): Although PTH levels are typically elevated in FHH, some cases may present with normal intact PTH levels due to the disorder's variable expression and the specific mutation involved.
- Hyperthyroidism: Elevated thyroid hormones can increase bone resorption, leading to hypercalcemia. Intact PTH levels may be normal or slightly decreased in an attempt to counteract the hypercalcemic effect.
Do Not Miss Diagnoses
- Primary hyperparathyroidism with PTH assay interference: Although intact PTH is reported as normal, certain conditions (e.g., heterophile antibodies, biotin interference) can falsely lower PTH measurements. It's crucial to consider this possibility, especially if clinical suspicion for primary hyperparathyroidism remains high.
- Vitamin A intoxication: Similar to vitamin D, excessive intake of vitamin A can cause hypercalcemia. This condition is less common but can have severe consequences if not recognized and treated promptly.
Rare Diagnoses
- Sarcoidosis: This granulomatous disease can lead to increased production of 1,25-dihydroxyvitamin D by macrophages within granulomas, resulting in hypercalcemia. Intact PTH levels are typically normal or decreased in response to the elevated calcium.
- Williams syndrome: A rare genetic disorder characterized by hypercalcemia due to increased sensitivity to vitamin D. Intact PTH levels may be normal, and the condition is often associated with distinctive facial features and developmental delays.
- Immobilization hypercalcemia: Prolonged immobilization, especially in young individuals with high bone turnover (e.g., those with spinal cord injuries), can lead to hypercalcemia due to increased bone resorption. Intact PTH levels are usually normal in this context.