Y5 - Hypercalcaemia of malignancy

Question 1

what does hypercalcaemai of malignancy result from

Answer 1

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)

Question 2

what is most commonly used to treat hypercalcaemia of malignancy

Answer 2

IV biphosphonates

Question 3

how common is malignancy associated with hypercalcaemia of malignancy

Answer 3

25% o cases

Question 4

what four factors could lead to hypercalcaemia of malignancy

Answer 4

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)

Question 5

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

Answer 5

renal cancer
ovarian cancer
breast cancer
endometrial cancer
squamous cell cancer

Question 6

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

Answer 6

breast cancer

multiple myeloma

Question 7

what is assoicated with calcitriol mediated hypercalcaemia

Answer 7

lymphoma
sarcoid
TB

Question 8

how does humoral hypercalcaemia work

Answer 8

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

Question 9

what happens to phosphate levels in humoral hypercalcaemia

Answer 9

hyperphospaturia and hypophosphataemia

Question 10

how does local osteolytic hypercalcaemia occur

Answer 10

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

Question 11

how does calcitriol mediated hypercalcamia work

Answer 11

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

Question 12

epi

Answer 12

most common is humoral hypercalcaemia of malignancy

Question 13

signs and symptoms

Answer 13

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

Question 14

investigations

Answer 14

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

Question 15

what would be found on ECG

Answer 15

shortened QT interval

Question 16

mneumonic for symptoms of hypercalcaemia

Answer 16

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

Question 17

approach to management

Answer 17

long-term maintenance of normocalcaemia requires eradication of malignancy

Question 18

management

Answer 18

IV saline
IV biphosphonate
calcitonin

treat underlying malignancy

Question 19

what medications should be avoided which can worsen hypercalcaemia

Answer 19

thiazide diuretics
calcitriol
lithium

Question 20

what is the first line therapy for hypercalcaemia and why

Answer 20

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

Question 21

what is the best treatment for reducing calcium levels

Answer 21

IV biphosphonates

-block osteoclastic bone resorption

Question 22

what biphosphonates are used

Answer 22

pamidronate disodium

zoledronic acid

Question 23

why might calcitonin be used to treat hypercalcaemia

Answer 23

interferes with osteoclast bone resorption

Question 24

first line treatment for mild hypercalcaemia or asymptomatic

Answer 24

treat underlying malignancy

Question 25

which works faster, biphosphonates or calcitonin

Answer 25

calcitonin (given while waiting for effects of biphosphonates)

Question 26

management for severe hypercalcaemia with advanced kidney disease

Answer 26

renal dialysis

Question 27

complications

Answer 27

biphosphonate induced flu like syndrome (aches, fever, chills)

Question 28

prognosis

Answer 28

IV saline, biphosphonates can temporarily induce normocalcaemia
however eradication of malignancy is required for long term effects