Hypercalcaemia of malignancy and hypocalcaemia Flashcards
Does hypocalcaemia cause bradycardia?
Hypocalcaemia is associated with a prolonged QT interval rather than bradycardia.
What is the most likely diagnosis and why?
- Constipation related to medication
- Hypercalcaemia
- Pancreatitis
- Large bowel obstruction
- Perforated abdominal viscus
- Urinary tract infection
- Chest infection
- Cerebral metastases
What must you exclude?
Hypercalcaemia - intermittent confusion, non-specific pain, constipation suggests hypercalcaemic crisis in a patient with known bone mestastases.
Must exclude pancreatitis, sepsis, and perforation so do MSU, CXR, AXR, serum calcium, LFT’s, amylase.
Low phosphate and low magnesium may occur with hypercalcaemia, as well as ECG abnormalities. Hypercalcaemia, is due to increased osteoclast activity. Renal failure and dehydration may also arise secondary to hypercalcaemia.
What does this show?
- Normal bowel gas pattern
- Sclerotic bony metastases are evident
What is the aetiology of hypocalcaemia?
Failure of any mechanism by which serum calcium is maintained. Usually due to failure of the parathyroid gland
Response to low calcium:
- Osteoclast activation
- Increased gut absorption
- Kidney retains calcium - 1 -alpha hydroxylase is activated in the kidney
What are the risk factors for hypocalcaemia?
Severe vitamin D deficiency
- Renal failure
- Anticonvulsant use
- Lack of sunlight
- Chappatis (phytic acid)
Parathyroid surgery - ‘hungry bone syndrome’
Mg2+ deficiency e.g. PPI associated
Cytotoxic drugs
Pancreatitis, rhabdomyolysis and large volume blood transfusions
How does a low albumin state affect calcium levels?
Bound Ca will be low but free calcium will be normal
About 40% of Ca is bound to albumin so measuring it is essential to diagnosis
45% circulates as biologically active Ca in ionised state
15% is bound to sulfates, phosphates, lactate and citrate
Which type of hyperparathyroidism causes low calcium?
Secondary hyperparathyroidism
What happens to calcium if you have high dietary phosphate intake?
Low calcium because phosphate binds calcium in the kidneys and they are both lost
What is shown on this ECG?
An adjusted QT interval (QTc) of 503 ms while in sinus rhythm = hypocalcaemia
Normal QTc = 350 to 450 ms for adult men and from 360 to 460 ms for adult women
What is the clinical effect of hypocalcaemia (on examination)?
- Neuromuscular excitability
- Trousseau’s sign - when you take BP then you have more albumin. This binds the already low Ca and causes carpal spasm (flexion of the fingers).
- Chvostek’s sign
- Convulsions
NB: these signs will only be seen if Ca falls rapidly; not if chronically low Ca
What investigations should be done in hypocalcaemia?
- Serum total Ca adjusted for albumin
- Albumin
- PTH
- 25-hydroxyvitamin D
- Renal function
- Magnesium
- Amylase/lipase
- Cr, CK
- FBC - T cell counts for ?Di George syndrome
- ECG
Imaging:
- XR for fractures in osteomalacia
- Isotope bone scans - metastases
At what level does hypocalcaemia usually become symptomatic?
<1.9mmol/L but this also depends on the rate of the fall
What is the management of acute severe (<1.9mmol/L) hypocalcaemia?
Aim is to improve symptoms and not to return Ca back to normal. Ca replacement:
- IV calcium gluconate infusion - 10–20 mL 10% calcium gluconate in 50–100 mL of 5% dextrose i.v. over 10 min with ECG monitoring; repeat until patient is asymptomatic
Treat underlying cause e.g. long term Ca treatment of 0.25-0.5mcg/day; in post-operative hypocalcaemia and other cases of hypoparathyroidism, this consists of alfacalcidol or calcitriol therapy.
What is the management of mild hypocalcaemia (>1.9mmol/L and asymptomatic)?
Oral calcium supplements e.g. Calcichew 2 tablets BD
- If Vitamin D is the cause supplement this e.g. 300,000 Units over 6-10weeks
Stop precipitants and treat underlying condition
What bone pathology is caused by long-standing hyperparathyroidism?
Osteitis fibrosa
What are the complications associated with hypocalcaemia management?
- Local thrombophlebitis
- Cardiotoxicity
- Hypotension
- Calcium taste
- Flushing
- N&V
- Sweating
- Arrhythmias (especially if also on digoxin or preexisting arrhythmias)
Which malignancies cause hypercalcaemia?
Small cell lung Ca due to PTHrP
Bone metastases
Haematological malignancy e.g. myeloma
What are the clinical features of hypercalcaemia?
- Polyuria and thirst
- Anorexia, nausea and constipation
- Mood disturbance, cognitive dysfunction, confusion and coma
- Renal impairment
- Shortened QT interval and dysrrhythmias
- Nephrolithiasis, nephrocalcinosis
- Pancreatitis
- Peptic ulceration
- Hypertension, cardiomyopathy
- Muscle weakness
- Band keratopathy
What are the most common causes of hypercalcaemia?
90% due to primary hyperparathyroidism or malignancy
Other causes:
- Thiazide diuretics
- Familial hypocalcuric hypercalcaemia
- Granulomatous disease
- Thyrotoxicosis
- Tertiary hyperparathyroidism
- Hypervitaminosis D or A
- Adrenal insufficiency
At what level does hypercalcaemia become symptomatic?
>3.5mmol/L - requires correction due to risk of dysrhythmia and coma
Although may be symptomatic at levels >3mmol/L
What investigations would you do for hypercalcaemia?
- Fluid balance
- ECG - short QT interval
- Calcium adjusted for albumin
- Phosphate
- PTH
- U&Es
What is the acute management of hypercalcaemia?
-
FLUIDS - 0.9% saline IV - 1L over 1 hour; 4-6L in 24hrs
- Monitor for fluid overload - loop diuretics will not reduce the serum Ca if overload occurs
- Dialysis if renal failure
- Zoledronic acid 4mg over 15min - if fluids alone fail, give bisphosphonates. Monitor serum Ca in the next 2-4 days.
-
Treat underlying cause - to know the diagnosis measure the PTH before you give bisphosphonates.
- ?parathyroidectomy
- ?glucocorticoids in lymphoma or other granulomatous diseases
- ?calcitonin, calcimimetics, denosumab
- Stop thiazides and Ca supplements
Why is hypercalcaemia in malignancy diagnosed late sometimes?
Because it mimics the symptoms of terminal malignancy
What is the prognosis of hypercalcaemia of malignancy?
Those admitted for hyper Ca of malignancy have a 50% 30-day mortality
How common is hypercalcaemia of malignancy?
Affects 1.5%
What are the side effects of bisphosphonates in the treatment of hypercalcaemia?
- Transient flu like syndrome with aches fevers and chills
- Bone an d joint pain
- Nausea
- Electrolyte imbalance
Rarely:
- Osteonecrosis of the jaw
- Acute renal failure
