Can Anastrozole Cause Primary Hyperparathyroidism?
No, anastrozole does not cause primary hyperparathyroidism, but there is one documented case report where it induced severe hypercalcemia with elevated PTH levels that mimicked primary hyperparathyroidism. 1
The Critical Distinction
Primary hyperparathyroidism is a disorder of the parathyroid glands themselves, most commonly caused by parathyroid adenomas, and is the most frequent cause of hypercalcemia in ambulatory patients, particularly postmenopausal women. 2 Anastrozole does not cause this condition.
However, anastrozole can rarely cause a secondary hypercalcemic state that biochemically resembles primary hyperparathyroidism but is fundamentally different:
The Single Case Report Evidence
- A 65-year-old woman on anastrozole developed severe hypercalcemia (adjusted serum calcium 3.39 mmol/L) with elevated PTH levels 2.5 years after starting treatment. 1
- Surgical neck exploration revealed only normal parathyroid glands, confirming this was not true primary hyperparathyroidism. 1
- When anastrozole was withdrawn, the hypercalcemia resolved within 2 weeks and actually converted to hypocalcemia. 1
- Re-challenge with anastrozole reproduced the severe hypercalcemia and elevated PTH within 6 weeks. 1
- Urinary calcium excretion was paradoxically very low during anastrozole treatment (unlike typical primary hyperparathyroidism) and increased after drug cessation. 1
The Proposed Mechanism
The mechanism is unknown, but it is hypothesized that anastrozole may directly or indirectly interfere with calcium-sensing receptors on parathyroid and renal tubular cells. 1 This would represent a drug-induced disturbance of calcium homeostasis rather than a primary parathyroid disorder.
Known Bone-Related Effects of Anastrozole
The established bone effects of anastrozole are well-documented in guidelines and differ from hyperparathyroidism:
- Increased bone resorption and decreased bone mineral density at the spine and hip, leading to increased fracture risk (7.1% vs 4.1% with tamoxifen in the ATAC trial). 3
- Articular symptoms including joint stiffness, arthralgias, and arthritis are common adverse effects. 3, 4
- These effects result from estrogen deprivation rather than parathyroid dysfunction. 3
Clinical Implications
When to Suspect This Rare Complication
- If a patient on anastrozole develops unexplained hypercalcemia with elevated PTH, consider anastrozole as a potential cause before proceeding to parathyroid surgery. 1
- The key distinguishing feature is low urinary calcium excretion during the hypercalcemic episode, which is atypical for primary hyperparathyroidism. 1
- Temporary withdrawal of anastrozole with monitoring of calcium levels can help establish causality. 1
Standard Monitoring for Anastrozole
Before initiating anastrozole, clinicians must evaluate baseline fracture risk and measure bone mineral density, as recommended by ASCO guidelines. 3 However, routine monitoring of serum calcium or PTH is not standard practice unless hypercalcemia is suspected clinically.
Management Pitfall
Do not proceed directly to parathyroid surgery in patients on anastrozole with hypercalcemia and elevated PTH without first considering drug withdrawal and re-challenge if the clinical picture is atypical. 1 True primary hyperparathyroidism would not resolve with drug cessation.