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Horrible Hormones


hormones

Up until 4 years ago, I didn’t have a clue about hormones – it’s one of those things you just take for granted. However, hormones are vital to human health (male and female) and it’s only when things go wrong you suddenly appreciate how important they are ……..like a lot of other things in life I suppose!   My interest started when I was diagnosed with metastatic Neuroendocrine Tumours (NETs) in 2010.

This is a really complex area and to understand the hormone problems associated with Neuroendocrine Cancer, you need to have a basic knowledge of the endocrine and neuroendocrine systems.  I’ve no intention of explaining that (!) – other than the following high level summary:

  • Glands in the endocrine system use the bloodstream to monitor the body’s internal environment and to communicate with each other through substances called hormones, which are released into the bloodstream.  Endocrine glands include; Pituitary, Hypothalmus, Thymus, Pineal, Testes, Ovaries Thyroid, Adrenal, Parathyroid, Pancreas.
  • A Hormone is a chemical that is made by specialist cells, usually within an endocrine gland, and it is released into the bloodstream to send a message to another part of the body. It is often referred to as a ‘chemical messenger’. In the human body, hormones are used for two types of communication. The first is for communication between two endocrine glands, where one gland releases a hormone which stimulates another target gland to change the levels of hormones that it is releasing. The second is between an endocrine gland and a target organ, for example when the pancreas releases insulin which causes muscle and fat cells to take up glucose from the bloodstream. Hormones affect many physiological activities including growth, metabolism, appetite, puberty and fertility.
  • The Endocrine system. The complex interplay between the glands, hormones and other target organs is referred to as the endocrine system.
  • The Neuroendocrine System. The diffuse neuroendocrine system is made up of neuroendocrine cells scattered throughout the body.  These cells receive neuronal input and, as a consequence of this input, release hormones to the blood. In this way they bring about an integration between the nervous system and the endocrine system (i.e. Neuroendocrine).  A complex area but one example of what this means is the adrenal gland releasing adrenaline to the blood when the body prepares for the ‘fight or flight’ response in times of stress, ie, for vigorous and/or sudden action.

If you want a reasonably short explanation of the word ‘Neuroendocrine’ in the context of Neuroendocrine Cancer, check out my blog entitled “Neuroendocrine – what’s that?

So are hormones ‘horrible’ as my title indicates? Absolutely not, they are essential to the normal function of the human body.  For example if you didn’t have any of the hormone Serotonin in your system, you would become extremely ill.  On the other hand, if your glands start secreting too much of certain hormones, your body could become dysfunctional and in some scenarios, this situation could become life threatening.  So hormones are good as long as the balance is correct. However, they really get a bad press in the NET Cancer community!

I used the example of Serotonin above because it is the most cited problem with most common variant of NET Cancer (a sub-type currently known as Carcinoid).  Serotonin is a monoamine neurotransmitter synthesized from Tryptophan, one of the eight essential amino acids (defined as those that cannot be made in the body and therefore must be obtained from food or supplements). About 90% of serotonin produced in the body is found in the enterochromaffin cells of the gastrointestinal (GI) tract where it is used mainly to regulate intestinal movements. The remainder is synthesized in the central nervous system where it mainly regulates mood, appetite, and sleep. There is no transfer of serotonin across the blood-brain barrier.

Other Neuroendocrine Cancer related hormones include (but not limited to); Neurokinin A (NKA), Substance P, Vasoactive Intestinal Peptide (VIP), Somatostatin, Chromogranin A (CgA), Gastrin, Insulin, Histamine, Glucagon, Calcitonin Gene-Related Peptide (CGRP), Pancreatic Polypeptide (PP).  At least one or more of these hormones will be involved at various sites and even within certain syndromes, the dominant and offending hormone may differ between anatomical tumour sites.

Sometimes the cause of the excessive hormone secretion is due to malignant cancer cells and my type of cancer falls into this category.  NETs of the small intestine, lung or appendix (and obe or two other places) may overproduce serotonin and other hormones which can cause a characteristic collection of symptoms currently called carcinoid syndrome.   The key symptoms are flushing, diarrhea and general abdominal pain, loss of appetite, fast heart rate and shortness of breath and wheezing. The main symptom for me was facial flushing and this was instrumental in my eventual diagnosis. The fact that I was syndromic at the point of diagnosis made it easier to discover, albeit the trigger for the investigation was a fairly innocuous event!

Excessive secretions or high levels of hormones and other substances can be measured in a number of ways but the main ones for the most common types of NET are Chromogranin A (CgA) blood test and 5-Hydroxyindoleacetic Acid (5-HIAA) 24 hour urine test (although this differs globally based on availability and specialist preferences). Others may be used at the diagnostic phase or during surveillance.  By measuring the level of 5-HIAA in the urine, healthcare providers can calculate the amount of serotonin in the body (5-HIAA is a by-product of serotonin).  5-HIAA test is the most common biochemical test for carcinoid syndrome or the degree of how ‘functional’ carcinoid tumours are.  If you’ve understood the text above, you can now see why there are dietary and drug restrictions in place prior to the test. CgA is a blood test which measures a protein found in carcinoid tumour cells. This test is normally associated with tumour mass rather than tumour activity/functionality.

One of the key treatment breakthroughs for NET cancer patients, particularly those who have shown symptoms of carcinoid syndrome, is ‘Somatostatin Analogues’, branded as Octreotide or Lanreotide (mainly). Patients will normally be prescribed these drugs if they are displaying these symptoms but some people may be more avid to the drug than others and this may influence future use and dosages. This is another complex area but I’ll try to describe the importance here in basic terms. Somatostatin is a naturally occurring protein in the human body. It is an inhibitor of various hormones secreted from the endocrine system and it binds with high affinity to the five somatostatin receptors found on secretory endocrine cells. Carcinoid tumors have membranes covered with receptors for somatostatin. However, the naturally occurring Somatostatin has limited clinical use due to its short half-life (<3 min). Therefore, specific somatostatin analogues (synthetic versions) have been developed that bind to tumours and block hormone release. Thus why Octreotide and Lanreotide do a good job of slowing down hormone production, including many of the gut hormones controlling emptying of the stomach and bowel.  It also slows down the release of hormones made by the pancreas, including insulin and digestive enzymes  (so there can be side effects including fat malabsorption). It’s also why Octreotide is used in radioactive scans as the mix of radioactivity and octreotide binds to the tumours making them ‘light up’ and show on the gamma camera pictures.  Prior to my initial surgery, daily Octreotide reduced my symptoms and the tumours identified on my CT scans all lit up (and some more!) on my initial and subsequent Octreotide Scans.

Other types of NETs are also affected by the overproduction of hormones including Insulinomas, Gastrinomas, Glucagonomas,VIPomas and Somatostatinomas.  If you want to read more detail I suggest the “5th edition handbook, Neuroendocrine Tumors: A Comprehensive Guide to Diagnosis and Management” which is available for download or a hard copy by post – contact ISI at requests@interscienceinstitute.com (they will even post to UK – it worked for me!). Table 1.1 on page 5 is a good starting point.

thanks for reading

Ronny
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12 Comments

  1. susanna2661 says:

    Overall good synopsis. I would disagree however about somatostatin anoligues normally being prescribed only after tumors have been shown to have avidity for them. In the US I think there is only one specialist actually testing tumors for stt2 receptor. It is not common practise to test for avidity in tumors. And I’m not certain that should be the standard for determining effectiveness of the somatostatin anoligues.

    Liked by 1 person

    • ronnyallan says:

      Thanks Susan, I think the tests for avidity are not particularly scientific and the comment was based on my own experience with my Oncologist who told me that as Octreotide daily reduced my flushing (pre-surgery) and that on Octreotide scan my tumours lit up in the same areas as tumours were showing on CT (and some more!), then I was clearly “Octreotide avid”. I’ll tweak it to allude to it being my own experience.

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  2. Sarah says:

    Another great one, Ronny! Thanks so much for continuously sharing the wealth of information you learn. Your blog is my favorite resource!

    Liked by 1 person

  3. cy says:

    One thing your readers should note is that none of the tests (5-HIAA, serotonin, CgA blood tests etc.) are a conclusive proof of the disease or progression. Many doctors only accept a biopsy of a tumor. In my case, the 5-HIAA was negative even though I already had a biopsy of a tumor and a mild syndrome and high blood serum serotonin. Currently, my blood serotonin and CgA are low average but new tumors are appearing in my liver!
    Thanks for your blog. You are always informative and quite accurate.
    Cy

    Liked by 1 person

    • ronnyallan says:

      Thanks Cy, as you know it’s difficult to condense every (if and but) scenario in a single blog but you’re right to say what you said – for some, even scans don’t produce sufficient evidence! However, the most common scenarios will be found using these tests (in relation to hormones – the blog subject)

      Liked by 1 person

  4. […] exhibit Carcinoid Syndrome indicating their tumours are functional (secreting excess hormones, particularly serotonin).  It follows that Carcinoid Syndrome is not that common!  It can also be […]

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  5. neilla edgar says:

    I was just wondering if you have any knowledge of epinephrine or any other medication that end in “ine” has being a No Dont take if you’re a carcinoid patient? I’m really find your blogs very beneficial for me. And on that note, thank you very much for all your time and info!!

    Liked by 1 person

  6. feefeemartin says:

    Hi Ronny,
    My name is Fiona Martin, I came across your blog as I have a similar diagnosis , slightly different, but a pancreatic neuroendocrine tumour. I’d like to discuss with you more, ive got my own blog on here too, my situation was v messed up this year as they discovered it as I was pregnant. I’d like you to read my blog/follow to and maybe private message/email me if you can?
    Many thanks
    Fiona

    https://feefeemartin.wordpress.com/

    Liked by 1 person

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