Multiple Myeloma and PTH Levels
Multiple myeloma does not typically cause low PTH levels; in fact, PTH is usually suppressed (low) in myeloma patients who develop hypercalcemia, which is a secondary physiological response to elevated calcium rather than a direct effect of the malignancy itself. 1, 2
Mechanism of PTH Suppression in Multiple Myeloma
When multiple myeloma causes hypercalcemia (the "C" in CRAB criteria), the elevated serum calcium physiologically suppresses parathyroid hormone secretion through normal negative feedback mechanisms. 1, 2 This represents appropriate parathyroid gland function responding to hypercalcemia, not a primary disorder of PTH production.
Key Biochemical Pattern in Hypercalcemic Myeloma:
- Elevated serum calcium from bone destruction and PTHrP production 2, 3
- Suppressed (low) PTH as a normal physiological response to hypercalcemia 2, 3, 4
- Suppressed 1,25(OH)₂ vitamin D₃ levels 2, 3
- Elevated PTH-related peptide (PTHrP) in many cases 2, 3, 4
The Role of PTHrP in Myeloma
PTHrP (parathyroid hormone-related peptide) is the actual culprit in many myeloma cases with hypercalcemia, not PTH itself. 2, 3, 4 Myeloma cells can produce PTHrP, which mimics PTH's bone-resorbing effects but is measured separately from PTH. 2, 5
- PTHrP is detected in myeloma cell cytoplasm by immunohistochemistry and in situ hybridization 2, 4, 5
- Plasma PTHrP levels correlate positively with corrected serum calcium levels in myeloma patients 3
- PTHrP acts both locally (paracrine) and systemically (endocrine) to increase bone resorption and calcium levels 2, 6
Critical Diagnostic Pitfall to Avoid
If you find low PTH in a myeloma patient with hypercalcemia, this is the expected finding and confirms myeloma-related hypercalcemia rather than primary hyperparathyroidism. 1 The guideline specifically warns that hypercalcemia from hyperparathyroidism (which would show elevated PTH) must be ruled out by checking PTH levels to avoid misdiagnosis. 1
Distinguishing Myeloma Hypercalcemia from Primary Hyperparathyroidism:
- Myeloma hypercalcemia: High calcium + Low PTH + often elevated PTHrP 2, 3, 4
- Primary hyperparathyroidism: High calcium + High PTH 1
Clinical Context
Low PTH in myeloma only occurs in the setting of hypercalcemia and represents appropriate parathyroid suppression. 2, 3 In normocalcemic myeloma patients, PTH levels remain in the normal range. 3 The frequency of elevated PTHrP is significantly greater in hypercalcemic versus normocalcemic myeloma patients (5/6 vs 2/9, p=0.02). 3