From the Guidelines
For a female patient with a history of frequent fragility fractures, kidney stones, and incidental hypercalcemia, I strongly recommend ordering parathyroid hormone (PTH) levels as the primary test. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of biochemical testing, specifically serum calcium and serum PTH, in diagnosing primary hyperparathyroidism (PHPT) 1. The clinical presentation of hypercalcemia, fragility fractures, and kidney stones in this patient is highly suggestive of PHPT, which is characterized by excessive PTH production, typically resulting in hypercalcemia.
The study published in the Journal of the American College of Radiology in 2021 highlights that PHPT is more common in women and can present with symptoms related to target organ involvement, including bone demineralization, fractures, nephrolithiasis, and nephrocalcinosis 1. Given this information, ordering PTH levels is crucial to evaluate for PHPT, which is the most likely diagnosis in this case.
Additional tests that may be helpful in the evaluation of this patient include:
- 25-hydroxyvitamin D levels to assess for vitamin D deficiency or insufficiency
- 24-hour urinary calcium excretion to evaluate for hypercalciuria
- Serum phosphorus, alkaline phosphatase, and renal function tests (BUN, creatinine) to assess for any renal or bone-related abnormalities
If primary hyperparathyroidism is confirmed with elevated PTH in the setting of hypercalcemia, further imaging studies such as parathyroid ultrasound, sestamibi scan, or 4D-CT may be warranted to localize the abnormal gland(s) prior to potential surgical intervention, as suggested by the study 1. Primary hyperparathyroidism causes increased bone resorption leading to fragility fractures and hypercalciuria resulting in kidney stone formation, making it the most probable underlying cause of this patient's constellation of symptoms.
From the Research
Additional Hormone Testing
To determine the underlying cause of hypercalcemia in a female patient with a history of frequent fragility fractures and kidney stones, additional hormone testing should be ordered.
- The patient's symptoms, such as hypercalcemia, skeletal fragility, and nephrolithiasis, are consistent with primary hyperparathyroidism (PHPT) 2, 3, 4.
- PHPT is characterized by hypercalcemia and elevated or inappropriately normal serum levels of parathyroid hormone (PTH) 4.
- The diagnosis of PHPT is confirmed in the presence of hypercalcemia and a normal or elevated PTH level in the absence of conditions that mimic PHPT 3.
- Therefore, ordering a PTH level test would be essential to confirm the diagnosis of PHPT.
Ruling Out Other Conditions
- Other conditions, such as vitamin D deficiency, can stimulate parathyroid secretion and contribute to hypercalcemia 5.
- However, vitamin D supplementation in patients with PHPT and vitamin D deficiency has been shown to reduce PTH levels without causing hypercalcemia and hypercalciuria 5.
- It is also important to rule out other conditions that can cause hypercalcemia, such as myeloma, lymphoma, and sarcoidosis 6.