Y5 - Hypercalcaemia of malignancy Flashcards

1
Q

what does hypercalcaemai of malignancy result from

A

1 secretion of parathyroid hormone related peptide by primary tumours
2 local release of factors which increase osteoclast proliferation/activity
3 production of calcitriol (1,25-dihydroxvitamin D) by lyphomas
4 production of PTH by primary tumours (rare)

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2
Q

what is most commonly used to treat hypercalcaemia of malignancy

A

IV biphosphonates

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3
Q

how common is malignancy associated with hypercalcaemia of malignancy

A

25% o cases

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4
Q

what four factors could lead to hypercalcaemia of malignancy

A

1 secretion of parathyroid hormone related peptide
2 release of factors including PTHrP to promote osteoclasts
3 calcitriol by lymphoma cells
4 ectopic hyperparathyroidism (PTH release from a primary tumour)

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5
Q

what is humoral hypercalcaemia (release of PTHrP) of malignancy associated with

A
renal cancer
ovarian cancer
breast cancer
endometrial cancer
squamous cell cancer
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6
Q

what is local osteolytic hypercalcaemia (promotion of osteoclasts) associated with

A

breast cancer

multiple myeloma

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7
Q

what is assoicated with calcitriol mediated hypercalcaemia

A

lymphoma
sarcoid
TB

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8
Q

how does humoral hypercalcaemia work

A

tumour secretion of PTHrP causes:
1 osteoclast bone resorption
2 suppression of osteoblast bone formation
causing an increase in calcium
also PTHrP reduces calcium clearance in the kidneys

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9
Q

what happens to phosphate levels in humoral hypercalcaemia

A

hyperphospaturia and hypophosphataemia

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10
Q

how does local osteolytic hypercalcaemia occur

A

cytokines (IL1/6), chemokines, and PTHrP cause increased osteoclast activity

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11
Q

how does calcitriol mediated hypercalcamia work

A

overexpression of 1-a hydroxylase (enzyme which converts 25-hydroxyvitamin D to calcitriol) by malignant cells which leads to autonomous production of bioactive vitamin D
vitamin D increases intestinal calcium absorption

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12
Q

epi

A

most common is humoral hypercalcaemia of malignancy

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13
Q

signs and symptoms

A

Hx of malignancy
often normal physical exam
sometimes signs of dehydration, fatigue, constipation, loss of appetite, polyuria, polydipsia

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14
Q

investigations

A
calcium studies
-raised total serum
-raised serum ionised 
serum albumin levels
metabolic panel
-raised urea and creatinine in AKI
-raised bicarbonate in malignancy
raised PTH or PTHrP
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15
Q

what would be found on ECG

A

shortened QT interval

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16
Q

mneumonic for symptoms of hypercalcaemia

A

“painful bones, renal stones, abdominal groans, and psychic moans,”

17
Q

approach to management

A

long-term maintenance of normocalcaemia requires eradication of malignancy

18
Q

management

A

IV saline
IV biphosphonate
calcitonin

treat underlying malignancy

19
Q

what medications should be avoided which can worsen hypercalcaemia

A

thiazide diuretics
calcitriol
lithium

20
Q

what is the first line therapy for hypercalcaemia and why

A

IV saline to reverse dehydration secondary to hypercalcaemia induced nephrogenic diabetes
PLUS oral rehydration

21
Q

what is the best treatment for reducing calcium levels

A

IV biphosphonates

-block osteoclastic bone resorption

22
Q

what biphosphonates are used

A

pamidronate disodium

zoledronic acid

23
Q

why might calcitonin be used to treat hypercalcaemia

A

interferes with osteoclast bone resorption

24
Q

first line treatment for mild hypercalcaemia or asymptomatic

A

treat underlying malignancy

25
which works faster, biphosphonates or calcitonin
calcitonin (given while waiting for effects of biphosphonates)
26
management for severe hypercalcaemia with advanced kidney disease
renal dialysis
27
complications
biphosphonate induced flu like syndrome (aches, fever, chills)
28
prognosis
IV saline, biphosphonates can temporarily induce normocalcaemia however eradication of malignancy is required for long term effects