Have seen a few patients with hypercalcemia recently and it has gotten me thinking. It is one of those areas of medicine where the complex endocrine physiology and diseases can seem a bit overwhelming. When we approach it in a practical sense it is much simpler than the head-spinning Med school lectures left us believing!
So lets break it down.
How high is high? The normal range for calcium in plasma is 2.2 – 2.6 mmol/l, however it is common to find “asymptomatic” mild hypercalcemia. I put asymptomatic in parentheses as the symptoms of early hypercalcemia can be very subtle, vague or easily mistaken for other diseases.
Generally hypercalcemic patients are consistently symptomatic at levels > 3.0 mol/l. Once one gets up above 3.5 mmol/l the more severe symptoms occur – this is an emergent situation.
Weakness, lethargy. malaise. Polyuria and polydipsia Table showing the common symptoms at presentation and how this has changed over the past 20 years from JAMA 2012. We seem to be diagnosing raised Ca more in asymptomatic patients or in the work-up for other common problems eg. osteoporosis, hypertension, depression
Acute renal failure might result in Vit D / Calcium toxicity if doses are not adjusted.
Severe secondary hyperparathyroidism can occur in chronic renal failure – as Hildy has reminded me – it is the tertiary hyperPTH that causes the hypercalcemia in chronic renal failure
Aluminum intoxication can cause raised Ca in dialysis
Management of Hyperclacemia
The management of hypercalcemia does to some extent depend on the underlying cause, however most of the causes are not readily remediable in the acute sense – hence we have treatments which can be applied to get the calcium down until the smart docs arrive and work out what is going on! Often the cause is readily apparent on the previous history – cancer, known endocrine disease, renal failure etc. So here is a quick skim through the management of hypercalcemia in the acute setting.
Patients with severe hypercalcemia are usually 4 – 6 litres down on water. So they need rehydration, especially if they have concomitant renal failure as a result. The decreased renal filtration results in a vicious cycle – they can then excrete less calcium. So correcting urine output is the key in the acute, severe patient.
Normal saline has been he traditional fluid used in this setting. Not much evidence to confirm or repute this practice and I imagine other IV fluids would also work – one needs to replace the lost electrolytes also – and this requires individualised monitoring. Fluid resuscitation alone will not likely reduce the calcium level much – so this is really a resuscitative measure.
Traditionally a loop diuretic such as frusemide has been used along with saline therapy – however this has come into question in recent years.
Largely this is because frusemide has little or no evidence base to show it helps and the introduction of newer, proven effective agents mean there is little role for this potentially harmful intervention. So in my practice I think I would prefer to use a drug that works, rather than one that might or might not be effective.
Bisphosphonates work by blocking bone reabsorption by osteoclasts. They are potent – in that they work well and consistently – but they do take a while to work. 24 – 48 hours is the peak activity. Traditionally they are used in malignant, bony disease, however they do work for other indications. They are also widely used in prophylaxis for patients with bony mets.
The main agents used are pamidronate and zoledronic acid – they are pretty safe and well tolerated – the one big risk is the development of osteonecrosis of the jaw in ongoing use. They are usually given as an infusion – ZA quickly, pamidronate slower.
Calcitonin (salmon) works as it does in nature by increasing renal excretion and also blocking osteoclast activity. Its onset of action is 4 – 6 hours – so faster than the bisphosphonates – and can be given at 5–10 units/kg daily by slow IV infusion. Another relatively safe choice, but not available in my small hospital.
So I think this one fits in as a front line agent in severe hypercalcemia where you want to get it down fast.
Steroids work by reducing intestinal reabsorption of calcium. They work on correcting overactive Vit D3 levels – so they work best in diseases such as sarcoidosis, TB or Vit D / D3 intoxication. This is a cheap and readily available option – but it is slow i.e, takes a few days to work. The dose is usually 25 – 50 mg per day.
Hydrocortisone can be given IV in the acute setting
I am a GP working in Broome, NW of Western Australia. I work as a hospital DMO (District Med Officer) doing Emergency, Anaesthestics, some Obstetrics and a lot of miscellaneous primary care. Also on the web as @broomedocs | + Casey Parker | Contact