Balancing Calcium — ASN Events
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Balancing Calcium (#359)

Jessie Teng 1 , Nirupa Sachithanandan 1 , Michael Hofman 2 , Richard MacIsaac 1
  1. Department of Endocrinology & Diabetes, St Vincent's Health, Melbourne
  2. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

A 38 year old man initially presented with severe hypercalcaemia (corrected calcium 4.50mmol/L) and acute kidney injury requiring haemodialysis. His past medical history was significant for renal calculi and primary hyperparathyroidism with previous parathyroidectomy. Humoral hypercalcaemia of malignancy was confirmed by an undetectable serum parathyroid hormone (PTH) level and elevated PTH-related peptide (PTHrP) level of 6.9pmol/L (normal <1.3pmol/L). Imaging revealed a large peri-nephric mass with bi-lobar hepatic metastases. Biopsy of the liver metastases revealed a well-differentiated neuroendocrine tumour (NET), but FDG and GaTaTate PET imaging revealed discordant disease.( His serum calcium normalised with intravenous pamidronate and hydration. However, his renal function remained abnormal (stage 3 chronic kidney disease – eGFR 35mL/min/1.73 m2).

He underwent six cycles of chemotherapy with carboplatin and etoposide. He also required two further doses of intravenous pamidronate to manage recurrent episodes of hypercalcaemia (corrected Ca 3.53mmol/L and 3.83mmol/L). In March 2013, he presented with a hypercalcaemic crisis (serum calcium 4.91mmol/L) and worsening renal failure (eGFR 13mL/min/1.73 m2). His hypercalcaemia was refractory to aggressive hydration, calcitonin and dexamethasone. Therefore, subcutaneous denosumab (120mg) was administered with rapid correction of hypercalcaemia. Ten days later, he presented with symptomatic hypocalcaemia, requiring intravenous calcium infusion and calcitriol. Four weeks on, he is still requiring twice weekly calcium infusions for corrected Ca <1.8mmol/L).

Genetic testing was positive for a heterozygous splice site mutation (c.931-2A>G(p.?)) in the MEN1 gene. He has undergone one cycle of palliative peptide-related radionuclide therapy, complicated by bone marrow suppression. Future anti-resorptive therapy for hypercalcaemic crisis is complicated by the impending need for dental extractions.


Discussion points:
 What are the therapeutic options for humoral hypercalcaemia of malignancy, occurring in the setting of impaired renal function?
 What is the optimal timing for dental interventions following anti-resorptive therapy?
 What are the management options for his neuroendocrine tumour?

1 

  1. Srirajaskanthan R, McStay M, Toumpanakis C, et al. Parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumours: case series and literature review. Neuroendocrinology 2009;89(1):48-55.
  2. Block GA, Bone HG, Fang L et al. A single-dose study of denosumab in patients with various degrees of renal impairment. Journal of Bone and Mineral Research 2012;27(7)1471-1479.
  3. Mundy GR, Edwards JR. PTH-related peptide (PTHrP) in hypercalcaemia. J Am Soc Nephrol 2008;19:672-5.
  4. Chattopadhyay N. Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy. Am J Physiol Endocrinol Metab 2006;290:E761-70.
  5. Morony S, Warmington K, Adamu S et al. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy. Endocrinology 2005;146(8):3235-43.
  6. Increase renal calcium reabsorption by parathyroid hormone-related protein is a causative factor in the development of humoral hypercalcemia of malignancy refractory to osteoclastic bone resorption inhibitors. Clin Cancer Res 2005;11:4198-203.
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