Thank you for joining the case. We’ve already met Mr Jones, a 75 year old man admitted following a fall to an orthopaedic ward with a fractured neck of femur. We agreed that his behaviour was new and odd and examined him throroughly – see the initial case update. We then obtained his blood results and established a number of abnormalities, specifically:
- Renal impairment
- Normocytic anaemia
- Elevated Alkaline Phosphatase
We subsequently discussed these results; the results of the discussion are summarised as follows:
This elevated result was in isolation from the rest of the LFTs, which are normal. This was felt most likely to be due to the recent femur fracture.
We had no previous results so were unsure as to the duration and cause of this abnormality. However this man had no past medical history that could easily explain the abnormalities seen. We discussed the possibility of a renal disease contributing to his health problems, but couldn’t readily tie this constellation of abnormalities together this way. We discounted Rhabdomyolysis as he hadn’t been immobile for prolonged periods or suffered major muscle trauma, which is the context in which we might expect rhabdomyolysis in a trauma setting.
The usual suspects for anaemia were discussed, and we agreed that it would be important to check Mr Jones’ haematinics. In addition the team wondered whether his renal impairment might explain his anaemia. Clearly this is an important differential diagnosis is a normocytic anaemia and can’t be discounted without knowing the chronicity of his renal disease. However there were other features of Mr Jones’ presentation to consider…
We all agreed that Mr Jones’ presentation fitted nicely for hypercalcaemia. In particular we noted that generalised abdominal pain, polyuria and confusion were all typical features of hypercalcaemia.
The cause for hypercalcaemia was discussed. Most of you wanted to check the patient’s parathyroid levels, which is very reasonable as this is a leadin cause of hyercalcaemia. However the patient’s other symptoms are not explained by hyperparathyroidism, and it is worth remembering Occam’s razor – i.e. a diagnosis that can explain all of Mr Jones’ problems is more likely than several disparate diagnoses. We’ll look a little further at this below.
Everyone agreed that the hypercalcaemia therefore needed treating. It was great to hear you all emphasise the importance of rehydration in the management of hypercalcaemia – this is something that qualified doctors forget about in their haste to reach for a bisphosphonate. But rehydrating the patient is important as they will be clinically dry – remember that polyuria is a key feature of hypercalcaemia. Mild hypercalcaemia can often be corrected simply with fluids. Some of you were anxious about fluid overload given the acute renal failure and history of cardiac disease. This is very sensible and the two tools to help with this are:
Starting a fluid balance chart, which will help you to decide how polyuric he is and thus how quickly you are able to fill him up.
Reassessing the patient. This can’t be emphasised enough. You want to rehydrate him and thus we agreed a bag of saline over 4 hours would be reasonable, but do reassess your patient at this point – has he passed urine? How much? Does he have an elevated JVP or basal creps on ausculatation? Is he feeling any better? From this point you can decide over what time period any further fluids should be prescribed.
The second point for the management of hypercalcaemia is the use of bisphosphonates. Most oncologists would use zolendronic acid, given as an IV bolus. There are two points to remember when using bisphosphonates however:
These drugs stop bony resorption and the subsequent release of calcium from the bone. They are not therefore immediately acting; their peak onset is seen at around 72 hours.
Bisphosphonates require renal adjustment. A great source for information on drugs and dosing is medicines.org.uk (eMC) which compiles all the specific product characteristics (SPCs) for drugs used in the UK. Always check drug doses when a patient has renal failure.
So, by 5 am you had successfully identified the key issue ata hand and instigated appropriate management of hypercalcaemia. Your final challenge was to think up a plan for fully investigating an managing this patient to impress your seniors on the morning ward round.
When all the problems are laid out here the constellation of problems – renal failure, anaemia, hypercalcaemia and a fracture – seem to obviously point to the diagnosis of myeloma. However in the case discussion, as in real life, the evolving narrative obscured the obvious. So a useful tip for real-life working is to constantly write problem lists for your patients. This allows:
- you to see the wood for the trees when you’re embroiled and confused by a complex patient;
- allows others to follow the patient’s progress without having to trawl through the notes;
- you to keep a track of issues that might otherwise be obscured by new problems;
- keep the patient’s concerns central to care, when they might get lost in medical issues.
Most of you felt that cancer was likely to be an issue for Mr Jones, but didn’t know where to start with investigating this. Your instincts seeemed to be against CT of whole body without a firm differential, which is good. There are some more basic tests to do first for Mr Jones. I would recommend discussing the femur film with the radiologist, as they may well be able to comment as to whether a pathological fracture has occurred. If so, and if you supply them with the other clinical problems Mr Jones has, they would probably recommend further plain films to look for bony lucencies which are the hallmark of myeloma. Please note that a bone scan is NOT useful in myeloma, as it relies on bony remodelling to highlight hot spots; in contrast there is no remodelling and thus no hotspots in myeloma and could falsely reassure you that there is ‘no cancer’.
In any patient with a pathological fracture, unexplained normocytic anaemia or hypercalcaemia it is important to look for myeloma. As a minimum you should request:
Serum immunoglobulins and electrophoresis
This will look for evidence of a monoclonal or paraprotein. Please remember that a polyclonal increase in immunoglobulins simply represents an active immune system and is not a feature of myeloma.
This looks for the overflow of serum free light chains from the serum into the urine, where they are called bence jones proteins (just to confuse you more!). In some labs the serum free light chains are automatically tested, but not always.
FBC, U&Es and Calcium (although already done in this case)
Plain xrays of any painful areas – the spine being the most common issue in this patient group.
Haematologists will usually request a skeletal survey at diagnosis, looking for lytic lesions in the bones. This is partly used to confirm the diagnosis (the presence of paraprotein does not, in itself, mean myeloma – end organ damage must usually be present for the label of myeloma to be used) but also to spot and treat any large lytic lesions to prevent pathological fractures.
Of note, blood films are rarely useful in Myeloma. This is because it is a disease of the bone marrow microenvironment and the malignant plasma cells rarely enter the circulating blood. When this does occur it is defined as plasma cell leukaemia and has a poor prognosis.
In summary, you successfully identified, managed and investigated a patient with hypercalcaemia, a common and significant oncology emergency.
I hope you found this case, and its evolving discussion, useful in your studies. Please continue to follow @teamhaem and visit the meded-hub.org.uk for learning opportunities.
Good luck with your studies!