Why PTH Overwhelms Calcitonin in Hypercalcemia
PTH does not actually "overwhelm" calcitonin—rather, calcitonin plays a minimal role in chronic calcium homeostasis in humans, and in primary hyperparathyroidism, calcitonin secretion is paradoxically normal or blunted despite chronic hypercalcemia. 1
The Calcitonin Response is Inadequate in Primary Hyperparathyroidism
The fundamental issue is that calcitonin does not mount an effective compensatory response to chronic hypercalcemia:
Basal calcitonin levels remain normal in patients with primary hyperparathyroidism despite persistent hypercalcemia, showing no elevation that would counteract the PTH-driven calcium elevation 1
Calcium-stimulated calcitonin secretion is blunted in hyperparathyroid patients compared to normal subjects, with significantly lower maximal increases during calcium infusion (P < 0.05) 1
The C-cell secretory reserve is decreased in primary hyperparathyroidism, and there appears to be an increased threshold of sensitivity for calcium stimulation of calcitonin secretion 1
After successful parathyroidectomy and restoration of normocalcemia, calcitonin responses to calcium infusion actually increase compared to preoperative values (Δ calcitonin: 13±4 pg/mL preoperatively vs 53±35 pg/mL postoperatively), demonstrating that the hypercalcemic state itself suppresses normal calcitonin responsiveness 1
PTH Mechanisms Dominate Calcium Regulation
PTH exerts multiple powerful effects on calcium homeostasis that are not effectively opposed by calcitonin:
PTH removes calcium from bone, leading to osteoporosis and sustained hypercalcemia in primary hyperparathyroidism 2
PTH increases renal calcium reabsorption and stimulates 1,25-dihydroxyvitamin D production, further enhancing intestinal calcium absorption 2
In primary hyperparathyroidism, PTH levels are elevated or inappropriately normal despite hypercalcemia, indicating autonomous secretion that is not suppressed by the elevated calcium 2, 3
Clinical Implications
The lack of effective calcitonin compensation explains why:
Hypercalcemia persists in primary hyperparathyroidism until the parathyroid tissue is surgically removed 2
Calcitonin administration can acutely lower calcium (by 3-5%) but does not provide long-term control, as demonstrated in treatment protocols where it serves only as adjunctive therapy 4
The only curative treatment for primary hyperparathyroidism is parathyroidectomy, since medical management cannot overcome the autonomous PTH secretion 2
A critical pitfall: Do not assume that calcitonin deficiency or resistance is the primary problem. The issue is that calcitonin simply lacks sufficient physiologic potency in humans to counteract pathologic PTH excess, and chronic hypercalcemia actually impairs what little calcitonin response exists 1