From the Guidelines
Genetic testing for Calcium-Sensing Receptor (CSAR) is not the primary approach in a patient with hypercalcemia, elevated calcium levels, and a family history of hypercalcemia, without a history of cancer, tuberculosis, or sarcoidosis.
Key Considerations
- The patient's presentation suggests primary hyperparathyroidism (PHPT), which is defined as hypercalcemia and an elevated or inappropriately normal concentration of PTH 1.
- PTH measurement is crucial in identifying patients with PHPT, and accurate measurement is essential to establish the diagnosis 1.
- The American Association of Endocrine Surgeons guideline for management of PHPT does not mention differences in PTH assays and does not give recommendations on this issue 1.
- Genetic testing may be considered in patients with a family history of hypercalcemia, but it is not the primary approach in this scenario.
Diagnostic Approach
- Serum calcium and intact parathyroid hormone (iPTH) measurement should be performed to diagnose hyperparathyroidism 1.
- 25-OH Vitamin D levels may be included to exclude hypovitaminosis D as a concomitant secondary cause of hyperparathyroidism 1.
- Imaging studies, such as ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT, may be performed to localize a parathyroid adenoma 1.
From the Research
Genetic Testing for Calcium-Sensing Receptor (CSAR)
- Genetic testing for CSAR is appropriate in patients with hypercalcemia, especially those with a family history of hypercalcemia, as it can aid in determining the etiology and appropriate therapeutic approaches 2.
- The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis, and study of the CASR gene can be clinically useful in diagnosing conditions such as familial hypocalciuric hypercalcemia (FHH) 3.
- FHH is characterized by mild to moderate hypercalcemia, hypocalciuria, and inappropriately normal or elevated parathyroid hormone (PTH) levels, and genetic testing can help differentiate it from primary hyperparathyroidism (PHPT) 4.
Indications for Genetic Testing
- A family history of hypercalcemia is a strong indication for genetic testing, as it can help identify genetic disorders such as FHH 5.
- Patients with hypercalcemia, elevated PTH levels, and hypocalciuria should undergo genetic testing to rule out FHH, especially if they have a family history of hypercalcemia 6.
- Genetic testing can also be useful in patients with hypercalcemia and no clear underlying cause, as it can help identify rare genetic disorders such as hypophosphatasia or renal phosphate wasting 5.
Importance of Genetic Testing
- Genetic testing can help confirm the diagnosis of FHH and distinguish it from PHPT, which is important for clinical management, as parathyroidectomy is ineffective in FHH 4.
- The identification of a novel heterozygous variant in the CaSR gene can support the diagnosis of FHH and highlight the significance of genetic testing in diagnosing this condition 3.
- Genetic testing can also help identify patients with a co-existing CaSR gene mutation and PHPT, which can inform clinical management and treatment decisions 6.