HaematologyTier 1Disease (DEADMAN)

Haematological emergencies - hypercalcaemia of malignancy

Description

Commonest life-threatening metabolic complication of malignancy
In haematology specifically: strongly associated with multiple myeloma and adult T-cell leukaemia/lymphoma
Corrected calcium >2.6mmol/L; severe/emergency generally >3.5mmol/L or symptomatic

Occurs in a substantial proportion of myeloma patients at some point in their course
Poor prognostic marker when it occurs in solid malignancy; in myeloma reflects high tumour/osteoclast burden

Mechanisms (haematological malignancy)

Myeloma - marrow plasma cells drive osteoclast activation (RANKL up, OPG down) -> local osteolysis -> humoral calcium release; PTHrP not typically the mechanism here (contrast solid tumours)
Lymphoma (esp. adult T-cell leukaemia/lymphoma, some NHL) - 1,25-(OH)2 vitamin D (calcitriol) production by tumour cells -> inc gut calcium absorption
Contrast solid tumours: PTHrP-mediated humoral hypercalcaemia of malignancy is the dominant mechanism there, not in most haematological disease

Corrected calcium (albumin-adjusted) or ionised calcium
PTH suppressed (distinguishes from primary hyperparathyroidism)
PTHrP - usually normal/low in haematological malignancy (raised in solid tumour humoral hypercalcaemia)
1,25-(OH)2 vitamin D - elevated in lymphoma-associated hypercalcaemia
Symptoms: "stones, bones, groans, psychiatric overtones" - polyuria/polydipsia (nephrogenic DI-like), constipation, confusion, bone pain
ECG - shortened QT interval

Immediate (moderate-severe or symptomatic)

IV isotonic saline - rehydration first, corrects volume depletion (often profound from polyuria/vomiting), 2-4L/24h guided by cardiac/renal status
IV bisphosphonate (zoledronic acid, or pamidronate if renal impairment) - once rehydrated, onset 2-4 days, effect lasts weeks
Calcitonin - rapid onset (hours) but short-lived and tachyphylaxis within days - bridges to bisphosphonate effect in severe cases
Avoid thiazides, limit calcium/vitamin D intake

Refractory / renal failure

Denosumab - alternative if bisphosphonate contraindicated (renal impairment) - RANKL inhibitor, fits myeloma mechanism directly
Dialysis - rare, for severe hypercalcaemia with renal failure unresponsive to above

Definitive

Treat the underlying malignancy - anti-myeloma therapy or lymphoma-directed chemo/immunotherapy is what durably controls calcium
Corticosteroids - useful adjunct in lymphoma (reduces calcitriol production) and myeloma

Multiple myeloma (lytic bone disease, renal impairment, anaemia, hypercalcaemia = CRAB criteria)
Adult T-cell leukaemia/lymphoma (HTLV-1 associated) - classically severe hypercalcaemia
Other NHL subtypes - less commonly

Untreated severe hypercalcaemia -> arrhythmia, coma, acute kidney injury, death
Nephrogenic diabetes insipidus-like picture -> volume depletion -> worsens calcium further (vicious cycle) - rehydration is not optional
Recurrence likely without effective control of the underlying malignancy

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