From the Research
When evaluating elevated calcium with normal parathyroid hormone (PTH) and normal vitamin D levels, focus on non-parathyroid causes of hypercalcemia, as suggested by the most recent and highest quality study 1.
Initial Steps
Begin with a thorough medication review to identify potential culprits like thiazide diuretics, lithium, or excessive calcium/vitamin D supplements.
- Order a comprehensive metabolic panel to assess kidney function, phosphorus, and albumin levels.
- Check for malignancy with a complete blood count, serum and urine protein electrophoresis, and consider chest X-ray and age-appropriate cancer screenings.
Further Evaluation
Evaluate for granulomatous diseases by testing for sarcoidosis (ACE levels), tuberculosis, and other inflammatory conditions.
- Thyroid function tests should be performed to rule out hyperthyroidism.
- Consider checking for familial hypocalciuric hypercalcemia with a 24-hour urine calcium and creatinine clearance.
- Adrenal function testing may be warranted to assess for adrenal insufficiency, as supported by the study on vitamin D-mediated hypercalcemia 2.
Rationale
This approach is necessary because normal PTH in the setting of hypercalcemia suggests either PTH-independent mechanisms or inappropriate normal PTH secretion when it should be suppressed, pointing to disorders of calcium sensing or non-parathyroid etiologies that require specific targeted treatments, as discussed in the review of hypercalcemia 1. The study on raised plasma concentrations of parathyroid hormone-related peptide in hypercalcemic multiple myeloma 3 also highlights the importance of considering malignancy in the differential diagnosis. However, the most recent and relevant study 1 provides the foundation for the recommended approach, prioritizing the evaluation of non-parathyroid causes of hypercalcemia.