Hypercalcaemia in Malignant Disease Quiz

Answer: A blood calcium level above normal.

Calcium has many important functions in the body including the development of teeth and bones. The normal serum level of calcium in the blood is between 2.2mmol/l and 2.6mmol/l.

Answer: Delayed onset (over 3-6 months).

The symptoms of hypercalcaemia, which also include rapid onset (over 1-3 weeks), drowsiness, lethargy, frequent urination and increased thirst, can often resemble symptoms of the underlying cancer and its associated treatments so it can be hard to diagnose. However the symptoms of hypercalcaemia develop rapidly and will continue to worsen without treatment.

Answer: False

Until recently the spread of cancer into the bone (bone metastases) was thought to be the primary cause of hypercalcaemia. However it is now thought to be more often due to parathyroid hormone-related peptide from the malignancy which is the primary cause of this condition.

This peptide imitates the action of the parathyroid hormone which works in three ways: it increases the action of the osteoclasts so calcium is resorbed from the bone; it increases the resorption of calcium in the kidneys and it stimulates the production of a vitamin (see question 6 for more information).

Answer: Bone.

Also involved in calcium homeostasis are the kidneys and the gastrointestinal tract (gut). When bone is formed/strengthened/renewed calcium is taken up from the blood and calcium is resorbed from the bone when the levels in the blood fall. Some calcium is excreted in the kidneys and absorbed from the gut.

Answer: Osteoblasts

Osteoblast cells form new bone by using up some of the calcium in the blood, causing the calcium level to fall. Osteoclast cells break down (resorb) bone and thereby make more calcium available raising the blood calcium level.

Answer: D

Whilst some vitamin D is absorbed from the gut the majority is made within the body when exposed to sunlight. One way that vitamin D works is to increase the blood calcium levels is by triggering the gut to absorb more calcium.

Answer: No

People with advanced malignant disease frequently suffer from low albumin levels in their blood. This is important because calcium becomes inactive when it binds to albumin but a low albumin is not taken into account with a total calcium recording (where all calcium, active and inactive is measured).

Therefore a calculation is made according to the person's albumin level and total calcium and a corrected or adjusted calcium level is given. It is the corrected calcium which will determine if a person is hypercalcaemic.

Answer: Rehydration.

Rehydration methods will vary according to the severity of the condition. Oral fluids may be adequate in some cases but often an intravenous isotonic saline solution will be necessary. Rehydration increases the renal blood volume and flow, maximising calcium excretion. For people with malignant disease rehydration is never sufficient alone to correct and maintain a normal calcium level.

Answer: Bisphosphonate therapy.

Two common bisphosphonates used in intravenous therapy are disodium pamidronate and zoledronic acid. Zoledronic acid is probably the stronger and more aggressive drug with a few more side effects, giving occasional flu-like symptoms, but is very effective. If there is a risk of causing post-treatment hypocalcaemia (low calcium) or a need to avoid certain side effects then disodium pamidronate may be the drug of choice. For a very high, life threatening calcium level zoledronic acid may be preferred. Ultimately the choice is made by the prescribing doctor.

Answer: Steroids.

Steroids appear to help in certain types of malignancy such as myeloma, lymphoma, leukaemia and breast cancer. In these cases steroids inhibit osteoclastic bone resorption and also reduce calcium absorption in the gut.
Laxatives can help the symptom of constipation but they will not help to correct the hypercalcaemia.

Answer: Thyroid gland.

Calcitonin is produced as a response to hypercalcaemia and works by reducing the action of the osteoclast cells responsible for bone resorption. This therapy works quickly and is effective enough to benefit patients, however the improvement is usually temporary and unsustained. Bisphosphonates tend, therefore, to be the treatment of choice.

Answer: Patients often die before the end of the study.

Hypercalcaemia can be a poor prognostic sign, especially in palliative care, where curative treatment has stopped. Even with very good control, prognosis remains poor as hypercalcaemia is often a sign that the disease is very advanced.

Answer: Yes

About sixty percent of the calcium in the blood is filtered through the kidneys and during this process some is resorbed and the rest is excreted in the urine. Unfortunately the kidneys do have a limit on the amount of calcium they can handle and if the level of calcium in the blood is too great, the kidneys will be unable to excrete enough and calcium levels will rise.

Answer: False

Once hypercalcaemia has occurred it is likely to recur, especially in patients for whom treatment of the causative malignancy is not possible. Patients and their families need to be aware to watch for symptom development and regular blood tests may also be required.

Answer: Osteonecrosis of the jaw.

The actual mechanism for this complication is unclear. There seems to be some evidence that the constant microtrauma from jaw movement and lack of adequate bone remodeling in the presence of bisphosphonates contributes to the development of osteonecrosis of the jaw.

However it should be remembered that this is a very rare condition, and whilst worth considering, is unlikely to counter-indicate the use of bisphosphonates to correct hypercalcaemia - as without correction, death would be imminent and with correction many more months of life may be enjoyed.