Differential Diagnosis for Hypercalcemia
The patient presents with hypercalcemia, low PTH, and a family history of hypercalcemia. The following differential diagnosis is organized into categories:
- Single most likely diagnosis
- Familial Hypocalciuric Hypercalcemia (FHH): This condition is characterized by hypercalcemia, low PTH, and a family history of hypercalcemia. The low 24-hour urine calcium and the presence of a similar condition in a family member (sister) support this diagnosis.
- Other Likely diagnoses
- Vitamin D-mediated hypercalcemia: Although the 25-hydroxy vitamin D level is normal, the ionized calcium is slightly elevated, which could indicate an abnormality in vitamin D metabolism.
- PTH-independent hypercalcemia: The low PTH level and the absence of parathyroid masses on imaging suggest a PTH-independent cause of hypercalcemia.
- Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)
- Malignancy-associated hypercalcemia: Although the PTHRP is negative, malignancy can cause hypercalcemia through other mechanisms, such as local osteolytic hypercalcemia or ectopic production of 1,25-dihydroxy vitamin D. Checking SPEP and ACE levels may help rule out multiple myeloma or sarcoidosis.
- Hyperparathyroidism with parathyroid hormone assay interference: Although the PTH level is low, assay interference or a rare parathyroid hormone variant could lead to a false-negative result.
- Rare diagnoses
- Williams syndrome: A rare genetic disorder characterized by hypercalcemia, intellectual disability, and distinctive facial features.
- Jansen's metaphyseal chondrodysplasia: A rare genetic disorder characterized by hypercalcemia, short stature, and metaphyseal dysplasia.
- Neonatal severe hyperparathyroidism: A rare genetic disorder characterized by severe hypercalcemia, parathyroid hyperplasia, and often a family history of hyperparathyroidism.
Next steps:
- Check SPEP and ACE levels to rule out multiple myeloma or sarcoidosis.
- Consider genetic testing for FHH or other genetic disorders.
- Evaluate the patient's renal function and consider a renal biopsy if necessary.
- Monitor the patient's calcium levels and adjust management accordingly.
- Consider a consultation with a geneticist or an endocrinologist for further evaluation and management.