Hypercalcaemia of melanoma: incidence, pathogenesis and therapy with bisphosphonates

Tumour-induced hypercalcaemia (TIH) is a frequent complication of advanced cancer but has been rarely reported in patients with malignant melanoma, an d its pathogenesis remains unexplored. We studied eight patients with TIH a nd melanoma. We determined the incidence and pathogenesis of this complicat ion and the effects of bisphosphonate therapy. The incidence of TIH in 751 patients with melanoma was 1.1%. All patients had liver and bone metastases at the time of hypercalcaemia. All patients had osteolytic lesions, most o ften multiple. The median survival was 30 days (range 4-136 days). After re hydration, the mean (+/- SEM) corrected calcium was 3.42 +/- 0.17 mmol/l. P arathyroid hormone levels were adequately suppressed and vitamin D concentr ations were normal. Serum osteocalcin, a marker of bone formation, was low, except in the two patients with renal insufficiency, whereas fasting urina ry calcium and hydroxylproline were increased, indicating inhibition of bon e formation and stimulation of bone resorption. Increased parathyroid hormo ne-related protein secretion was noted in only one patient. Three of four p atients became normocalcaemic after bisphosphonate therapy for a median dur ation of 2 weeks. In conclusion, hypercalcaemia is a rare complication of m elanoma. It occurs in the context of far advanced disease and is essentiall y due to aggressive lytic bone metastases with an uncoupling in bone turnov er. Bisphosphonates can offer short-term palliation. (C) 2001 Lippincott Wi lliams & Wilkins.