Abstract
Dear Editor:
Hypercalcemia of malignancy (HCM) is the most common life-threatening metabolic complication of malignancy and confers a poor prognosis. 1 Management and treatment of HCM is well reported in the literature; 1 however some patients do not respond to conventional treatment, the cause of which is unclear. Calcitonin has been used in the acute management of HCM. However there is no literature to consider its use beyond the acute phase of several days in the context of bisphosphonate resistance. This case highlights the potential use of longer-term calcitonin in bisphosphonate-resistant HCM.
The patient was diagnosed with squamous cell carcinoma of the bladder 10 years previously, and subsequently developed local metastases. She presented with recurrent episodes of symptomatic hypercalcemia. On each admission she received escalating doses of bisphosphonate therapy as well as intravenous fluid which gave a temporary improvement in symptoms. However, her calcium failed to fall to normal limits. She was subsequently commenced on calcitinon. Over a two week period it was administered initially at 100 units TDS increasing to 100 units QDS after four days. This resulted in a correction of her serum calcium which was maintained for eight days after stopping treatment. There was a marked reduction in symptoms previously attributed to hypercalcemia. Unfortunately her overall condition deteriorated and calcitonin was discontinued as she approached death. She died peacefully six days later.
Treatment of HCM should be aimed at both normalizing the serum calcium and treating the underlying cancer, where appropriate. Bisphosphonates are currently the treatment of choice for HCM. Unfortunately our patient had a minimal response to bisphosphonates, of which the underlying mechanism was unclear. Body et al. 2 reported that the relative resistance to pamidronate correlated positively with high pretreatment levels of PTHrP. The predominant mechanism of hypercalcemia in squamous cell cancer is ectopic release of PTHrP, resulting in markedly elevated levels, perhaps accounting for this patients' resistance to bisphosphonates.
Calcitonin is a potent hypocalcemic hormone with a rapid onset of action. It inhibits both osteoclastic activity and renal tubular resorption of calcium. 3 However its use is normally limited to only a few days due to the development of tachyphylaxis. 3 At publication, the longest reported use of calcitonin for treatment for HCM was five days. 4 Diskin et al. 5 reports the only other case of treatment of bisphosphonate-resistant malignant hypercalcemia with calcitonin. The patient had a rapid response to calcitonin but it was discontinued after only one dose as the patient refused any further treatment.
This is the first published case report that demonstrates the use of calcitonin in the treatment of bisphosphonate-resistant HCM beyond the initial acute phase and for up to 14 days with no evidence of tachyphylaxis. Management of HCM remains challenging. Bisphosphonates are the mainstay of treatment. Calcitonin is a useful adjunct in severe hypercalcemia where a prompt response is required; however further research is needed to determine if it would be a viable longer-term option in the event of bisphosphonate-resistance.