Mechanisms Of Hypercalcaemia In Malignancy

Milk is famous because it comes from animal breasts and is widely touted as a source of calcium.

https://static.simpsonswiki.com/images/thumb/3/3c/Malk.jpg/250px-Malk.jpg

In the body, calcium is primarily stored in bones and teeth, because it’s good to have a regulated amount circulating in the blood. You know, to avoid things going wrong.

Hypercalcaemia means too much calcium in the blood.

What controls calcium?

Parathyroid hormone (PTH) is a substance released from the parathyroid glands, which are 4 tiny structures located behind the thyroid gland.

https://68.media.tumblr.com/cf1138a8c09f8b9d32a63d399f7bebf9/tumblr_ntgujo9CT51uykqfqo2_1280.png

Let’s analyse this, like language-obsessed…language obsessors. Real poetic, yes.

Para: beside.

Thyroid: thyroid.

Gland: a bunch of cells that collectively secretes things.

https://s-media-cache-ak0.pinimg.com/736x/8a/d2/f5/8ad2f5e2dbc23c417c84a72c6b458691.jpg

Yet another medical acronym!

Why is PTH important?

Because PTH liberates calcium from bones into blood.

In political terms, PTH is the Joan Of Arc freeing the oppressed French calcium from the English occupation of bone.

But if there’s too much or too little PTH, the blood calcium level can be thrown off.

And yes, if your PTH is burnt at the stake, things will also not be good.

PTH 101

More PTH ==> more calcium release from bones ==> blood calcium level goes up.

Less PTH ==> less calcium release from bones ==> blood calcium level goes down.

Simplified mechanisms of hypercalcaemia in cancer

What are the ways in which blood calcium levels can be elevated? There are 2 main ones.

1. Too much PTH

Fake PTH

Most commonly, some cancers involve the release of PTH-related protein, a substance similar to PTH that isn’t PTH.

On investigation, endogenous PTH will be low, due to endocrine suppression. From blood tests, expect high PTH-related protein and low actual PTH; your body thinks there is enough PTH around, so it stops making as much. The fake PTH isn’t measurable according to normal PTH tests.

Real PTH

More uncommonly, a cancer can abnormally make its own PTH.

On investigation, endogenous PTH will be high, due to excessive production. Your parathyroids again stop making PTH because there’s too much already, but the extra PTH is measurable in blood because it’s actual PTH…even if it doesn’t come from the right place.

2. Too much calcium from other sources

Bones

If cancer spreads to bone, it can induce calcium release that way. The blood calcium level goes up.

Intestines

Cancer can make extra vitamin D, a substance that normally encourages intestinal calcium absorption.

If too much calcium is absorbed from the intestines, the blood calcium level rises.

Detailed mechanisms of hypercalcaemia in cancer

  1. PTH-related protein: most common cause of hypercalcaemia in non-metastatic solid tumours.
  2. Osteolytic lesions: caused by metastases to bone.
  3. Tumour-produced 1,25-dihydroxyvitamin D: most common cause of hypercalcaemia in Hodgkin lymphoma.
  4. Tumour-produced PTH: rare occurrence where the cancer makes its own PTH.

References

  1. UpToDate. (2016, August 22). Hypercalcemia of malignancy: Mechanisms. Retrieved 3 April 2017, from https://www.uptodate.com/contents/hypercalcemia-of-malignancy-mechanisms
  2. History.com. Joan of Arc relieves Orleans. Retrieved 3 April 2017, from http://www.history.com/this-day-in-history/joan-of-arc-relieves-orleans
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