Hypercalcemia and malignancy

Thanks Daniel for presenting a great case! This was a case of an elderly patient with subacute-chronic fatigue and constipation presenting with hypercalcemia with both elevated PTH and PTHrp.

Main points:

  • 1) Hypercalcemia of malignancy is associated with solid and liquid tumors: breast, lung, kidney cancer & multiple myeloma, lymphoma, leukemia (think: what causes lytic lesions? also squamous solid tumors)
  • 2) EKG findings include short QT intervals and wide T waves => a combination => Osborn waves
  • 3) The approach to hypercalcemia should involve considering PTH mediated and non-PTH mediated causes

Want to learn more?

Approach to lytic lesions

Here is an excellent NEJM with a nice table (table 1) referencing the differential dx for lytic lesions

How useful is a Chloride/ Phosphorus ratio?

Great PICO question associated with this one: A popular 1975 paper found that a chloride/ phosphorus ratio of >33 is sensitive and specific for primary hyperparathyroidism. It was calculated in 34 sugical patients with proven primary hyperparathyroidism and 50 patients with other causes with an average serum calcium of 12.1 with a proposed mechanism that primary hyperPTH -> low phosphorus and disruption with bicarb may lead to reabsorption with chloride. However, some concerns re the paper include that ectopic PTH and PTHrP may have similar mechanisms leading to low phosphorus and it would not work in renal failure or patients with borderline elevated calcium levels. So, something to think about ordering but would still be important to check PTH and PTHrp (tests that may have been much more difficult to order back then).

Treatment of hypercalcemia

Here are the common agents that are used to treat hypercalcemia and +/-

Normal saline: acts in 1-2 hours & Furosemide: acts in 1-2 hours

  • Why give NS and furosemide? – hypercalcemia -> nephrogenic diabetes insipidus w dehydration and AKI

Bisphosphonates: acts in 1-2 days; (side effects: AKI, osteonecrosis of the jaw)

Calcitonin: acts in 4-6 hours; IM or SQ

Steroids: acts in days; good for ectopic 1,25OH vitD

Cinacalcet: treatment of secondary hyperparathyroidism

Denosumab: hypercalcemia of malignancy that has not responded to bisphosphonates

Vitamin D: for PTH mediated and if patient has low 25OH vitamin D