Can Parathyroid Tumors Cause Elevated PTHrP?
Yes, parathyroid adenomas can produce PTHrP, though this is not their typical biochemical signature and should not be confused with the primary diagnostic pattern of primary hyperparathyroidism.
Key Biochemical Distinction
The critical point is that parathyroid adenomas characteristically produce elevated PTH (parathyroid hormone), not PTHrP 1. Primary hyperparathyroidism is diagnosed by the combination of hypercalcemia with inappropriately normal or elevated PTH levels 2. This contrasts sharply with malignancy-associated hypercalcemia, where PTHrP is elevated and PTH is suppressed 1, 3.
Evidence for PTHrP Production in Parathyroid Tissue
Despite the typical PTH-dominant pattern, research demonstrates that parathyroid adenomas can indeed produce PTHrP:
- 65% of parathyroid adenomas show immunoreactive PTHrP on immunohistochemical staining 4
- PTHrP is present in 74% of parathyroid adenomas and 86% of normal parathyroid tissue 5
- PTHrP and PTH can be co-secreted simultaneously from the same parathyroid cells via secretory granules through a regulated pathway 6
Cellular Distribution Pattern
The production of PTHrP in parathyroid tissue follows a specific cellular pattern:
- Oxyphil cells and transitional oxyphil cells are the primary producers of PTHrP in parathyroid adenomas, not chief cells 4, 5
- Chief cells predominantly produce PTH 4
- PTHrP expression increases with age in normal parathyroid tissue, correlating with the relative increase in oxyphil cells 5
- In adenomas with predominant oxyphil cells, PTHrP expression is higher 5
Clinical Implications and Diagnostic Approach
When to Suspect PTHrP vs. PTH
If hypercalcemia is present with a known or suspected parathyroid tumor:
- Measure both intact PTH and PTHrP simultaneously 1, 3
- Elevated PTH with normal/suppressed PTHrP = typical primary hyperparathyroidism 2
- Suppressed PTH with elevated PTHrP = humoral hypercalcemia of malignancy (suggests alternative diagnosis like occult malignancy, not parathyroid adenoma) 1, 3
Important Caveats
- The presence of PTHrP in parathyroid adenomas does not typically cause clinical hypercalcemia through PTHrP-mediated mechanisms 7
- PTHrP in parathyroid tissue likely functions through paracrine/autocrine mechanisms to regulate cell proliferation and differentiation, rather than systemic endocrine effects 5
- Parathyroid carcinoma (rare, <1% of cases) may produce a posttranslationally modified form of PTH that can be detected by third-generation PTH assays, but this is distinct from PTHrP 1
Diagnostic Pitfall to Avoid
Do not confuse the research finding that parathyroid adenomas contain PTHrP with the clinical presentation of primary hyperparathyroidism. The diagnosis of primary hyperparathyroidism remains based on elevated serum calcium with elevated or inappropriately normal PTH 1, 2. The PTHrP present in parathyroid adenomas is not the cause of the hypercalcemia in primary hyperparathyroidism 7.
Bottom Line for Clinical Practice
While parathyroid adenomas can produce PTHrP at the tissue level, this does not translate into elevated serum PTHrP levels or PTHrP-mediated hypercalcemia 4, 7, 6, 5. If a patient presents with elevated PTHrP and hypercalcemia, look for malignancy (especially squamous cell lung cancer) rather than attributing it to a parathyroid adenoma 1, 3.