Y5 - Hypercalcaemia of malignancy Flashcards
what does hypercalcaemai of malignancy result from
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)
what is most commonly used to treat hypercalcaemia of malignancy
IV biphosphonates
how common is malignancy associated with hypercalcaemia of malignancy
25% o cases
what four factors could lead to hypercalcaemia of malignancy
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)
what is humoral hypercalcaemia (release of PTHrP) of malignancy associated with
renal cancer ovarian cancer breast cancer endometrial cancer squamous cell cancer
what is local osteolytic hypercalcaemia (promotion of osteoclasts) associated with
breast cancer
multiple myeloma
what is assoicated with calcitriol mediated hypercalcaemia
lymphoma
sarcoid
TB
how does humoral hypercalcaemia work
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
what happens to phosphate levels in humoral hypercalcaemia
hyperphospaturia and hypophosphataemia
how does local osteolytic hypercalcaemia occur
cytokines (IL1/6), chemokines, and PTHrP cause increased osteoclast activity
how does calcitriol mediated hypercalcamia work
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
epi
most common is humoral hypercalcaemia of malignancy
signs and symptoms
Hx of malignancy
often normal physical exam
sometimes signs of dehydration, fatigue, constipation, loss of appetite, polyuria, polydipsia
investigations
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
what would be found on ECG
shortened QT interval
mneumonic for symptoms of hypercalcaemia
“painful bones, renal stones, abdominal groans, and psychic moans,”
approach to management
long-term maintenance of normocalcaemia requires eradication of malignancy
management
IV saline
IV biphosphonate
calcitonin
treat underlying malignancy
what medications should be avoided which can worsen hypercalcaemia
thiazide diuretics
calcitriol
lithium
what is the first line therapy for hypercalcaemia and why
IV saline to reverse dehydration secondary to hypercalcaemia induced nephrogenic diabetes
PLUS oral rehydration
what is the best treatment for reducing calcium levels
IV biphosphonates
-block osteoclastic bone resorption
what biphosphonates are used
pamidronate disodium
zoledronic acid
why might calcitonin be used to treat hypercalcaemia
interferes with osteoclast bone resorption
first line treatment for mild hypercalcaemia or asymptomatic
treat underlying malignancy
which works faster, biphosphonates or calcitonin
calcitonin (given while waiting for effects of biphosphonates)
management for severe hypercalcaemia with advanced kidney disease
renal dialysis
complications
biphosphonate induced flu like syndrome (aches, fever, chills)
prognosis
IV saline, biphosphonates can temporarily induce normocalcaemia
however eradication of malignancy is required for long term effects
