Don’t be underactive with your Thyroid surveillance


thyroid

From other posts, you’ll be aware of the thyroid lesion (now 17x19mm) which I’ve been tracking since 2013. The surveillance has included routine thyroid blood tests, mainly TSH, T3 and 4. Due to trends in TSH and T4, it’s been suggested I’m borderline hypothyroidism. I’m out of range in TSH (elevated) but the T4 is currently at the lower end of the normal range.  On 20 March 2018, following an Endocrine appointment, I was put on a trial dose of 50mcg of Levothyroxine to counter the downwards trend in results indicating hypothyroidism. Levothyroxine is essentially a thyroid hormone (thyroxine) replacement.  One month after taking these drugs, my thyroid blood levels are now normal for the first time in 4 years (since there are records of test results – it might be longer).

The NET Connection?

To put things into context, hypothyroidism is an extremely common condition and the main treatment is administration of thyroid hormone  replacement therapy (i.e. Lewvothyroxine).  This is in the top 5 of the most commonly prescribed medication in USA and UK.

However, there are connections with NETs.  Firstly there is one type of cancer known as Medullary Thyroid Cancer (MTC) and it also has a familial version known as Familial MTC or FMTC.

There are also connections between regular Neuroendocrine Tumours (NETs) and the  thyroid.  It can often be a site for metastasis, something I have not yet written off given it lights up on nuclear scanning – although my biopsy was inconclusive.   You can see a summary of the connections and my own thyroid issue in more detail in my article “Troublesome Thyroids”. Please note the parathyroid glands are beyond the scope of this article.

Thyroid Function – the Lanreotide/Octreotide connection

Before I continue talking about hypothyroidism, here’s something not very well-known: Somatostatin analogues might cause a “slight decrease in Thyroid function” (a quote from the Lanreotide patient leaflet). The Octreotide patient leaflet also states “Underactive thyroid gland (hypothyroidism)” as a side effect. Many sources indicate that thyroid function should be monitored when on long-term use of somatostatin analogues. It’s also possible and totally feasible that many NET patients will have thyroid issues totally unrelated to their NETs. Remember, NET patients can get regular illnesses too!

What is Hypothyroidism?

Hypothyroidism is a condition in which your thyroid gland doesn’t produce enough of thyroxine. This leads to an underactive thyroid. It seldom causes symptoms in the early stages, but over time, untreated hypothyroidism can cause a number of health problems, such as obesity, joint pain, infertility and heart disease. Both men and women can have an underactive thyroid, although it’s more common in women. In the UK, it affects 15 in every 1,000 women and 1 in 1,000 men. Children can also develop an underactive thyroid.

What causes Hypothyroidism?

  • Autoimmune thyroid disease sometimes called Hashimoto’s thyroiditis
  • Radioactive iodine or surgery to correct hyperthyroidism or cancer
  • Over-treatment of hyperthyroidism with anti-thyroid drugs
  • Some medicines
  • A malfunction of the pituitary gland

What are the symptoms of Hypothyroidism?

The signs and symptoms of hypothyroidism vary, depending on the severity of the hormone deficiency. But in general, any problems you have tend to develop slowly, often over a number of years. At first, you may barely notice the symptoms of hypothyroidism, such as fatigue and weight gain, or you may simply attribute them to getting older. But as your metabolism continues to slow, you may develop more-obvious signs and symptoms. Hypothyroidism signs. Below are major symptoms associated with hypothyroidism:

    • Fatigue
    • Weakness
    • Weight gain or difficulty losing weight (despite reduced food intake)
    • Coarse, dry hair and dry skin
    • Hair loss
    • Sensitivity to cold
    • Muscle cramps and aches
    • Constipation
    • Depression
    • Irritability
    • Memory loss
    • Abnormal menstrual cycles
    • Decreased libido
    • Slowed speech (severe cases)
    • Jaundice (severe cases)
    • Increase in tongue size (severe cases)

Check out this excellent short video from WebMD – click here or the picture below.  It’s based on USA but most of it is relevant globally.

thyroid video webmd

You don’t have to encounter every one of these symptoms to be diagnosed with hypothyroidism. Every patient’s experience with the disorder is different. While you may notice that your skin and hair have become dry and rough, another patient may be plagued more by fatigue and depression.

When hypothyroidism isn’t treated, signs and symptoms can gradually become more severe. Constant stimulation of your thyroid gland to release more hormones may lead to an enlarged thyroid (goiter). In addition, you may become more forgetful, your thought processes may slow, or you may feel depressed.

Now ….. some of these symptoms look very familiar to me and they also look very familiar to some of the comments I see on patient forums related to somatostatin analogues and some of the NET syndromes – that jigsaw thing again. I guess it’s possible that people are borderline hypothyroidism prior to taking somatostatin analogues and the drug pushes them out of range (similar to what it’s known to do with blood glucose levels and diabetes). I’m not suggesting a direct clinical link in all cases but what I am suggesting is that perhaps some of the answers might be found in checking Thyroid hormone levels.

What are the Thyroid Hormone tests for Hypothyroidism?

A high thyroid stimulating hormone (TSH) level with a low thyroxine (T4) level indicates hypothyroidism. Rarely, hypothyroidism can occur when both the TSH and T4 are low. A slightly raised TSH with a normal T4 is called subclinical, mild, or borderline hypothyroidism. Subclinical hypothyroidism can develop into clinical or overt hypothyroidism

Routine ‘Thyroid blood tests’ from your doctor will confirm whether or not you have a thyroid disorder. I now test for TSH (thyroid-stimulating hormone), T4 every 6 months. Mostly in range but recently TSH is spiking out of range and T4 is consistently at the lower end of normal range.

Can hypothyroidism be treated?

Yes. A synthetic version of thyroxine taken daily as prescribed. e.g. Levothyroxine tablets

OK that’s Hypothyroidism – what is Hyperthyroidism?

Hyperthyroidism is a condition where the thyroid gland produces too much thyroid hormone for the body’s needs. It is also known as an overactive thyroid or thyrotoxicosis. An overactive thyroid can affect anyone, but it’s about 10 times more common in women than men and it typically starts between 20 and 40 years of age.

      • Hyper – means “over -“
      • Hypo – means “under -“
      • The terms “hyperthyroid” and “thyrotoxic” are interchangeable

Causes

      • Graves’ disease – the most common cause
      • A toxic nodular goitre (a goitre is an enlarged thyroid gland)
      • A solitary toxic thyroid adenoma (an adenoma is a clump of cells)
      • Thyroiditis (infection or inflammation of the thyroid gland) which is temporary

Common Symptoms

A speeding up of mental and physical processes of the whole body, such as

      • weight loss, despite an increased appetite
      • palpitations / rapid pulse
      • sweating and heat intolerance
      • tiredness and weak muscles
      • nervousness, irritability and shakiness
      • mood swings or aggressive behaviour
      • looseness of the bowels
      • warm, moist hands
      • thirst
      • passing larger than usual amounts of urine
      • itchiness
      • an enlarged thyroid gland

If the cause is Graves’ disease, you may also have ‘thyroid eye disease’. Smokers are up to eight times more likely to develop thyroid eye disease than non-smokers.

Diagnosis

      • By a physical examination and blood tests
      • A low thyroid stimulating hormone (TSH) level with a high thyroxine (T4) level indicate hyperthyroidism

Treatment Options

      • Antithyroid drugs
      • Surgery to remove all or part of the thyroid gland
      • Radioactive iodine to destroy most of the thyroid tissue

Research sources used to compile this post:

1. Lanreotide Patient Leaflet.

2. Octreotide Patient Leaflet.

3. British Thyroid Foundation. (particularly how to interpret Thyroid results – click here) – always check the unit of measure when comparing blood result ranges)

4. The UK NHS – Hypothyroidism (under active) and Hyperthyroidism (over active)

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Serotonin – the NET effect

A team of researchers from Case Western Reserve University School of Medicine have used high-powered microscopes for the first time to view serotonin activating its receptor

Background

I’d never heard of Serotonin until I was diagnosed with Neuroendocrine Cancer in 2010.  It is frequently discussed, often with contrasting views from the respondents. One common assumption/question is that it is responsible for many things that can go wrong with Neuroendocrine Cancer patients who have serotonin-producing tumours. “It’s the hormones” is an easy assumption to make or an easy answer to give in response to a complex set of circumstances.  It’s difficult to get a definitive answer and the science behind the behaviour of our hormones isn’t really 100% tied down.

You may see serotonin referred to as a ‘neurotransmitter’, a ‘chemical’ and a ‘hormone’ – this is complex but it is my understanding that it can add context in respect the role/location of the serotonin, e.g. chemical and hormone are essentially synonymous and are endocrine related whereas neurotransmitter is concerned with the nervous system (the neuro in neuroendocrine) and the brain (more on this below). Consequently, I’ll keep this as basic as I can (author’s note on completion – it was not easy!).

Serotonin and NETs

One thing which is widely accepted and agreed…… Serotonin is definitely involved in Neuroendocrine Tumours, in particular, those resulting in carcinoid syndrome which can manifest as a number of symptoms including but not limited to flushing and diarrhea.  Although serotonin is one of the main ‘hormones’ released in excess by certain NETs (mainly midgut), it is not thought to be the main culprit behind some of the symptoms produced by Carcinoid Syndrome.  For example, flushing, the most common symptom (and a cardinal one) is thought to be caused by a number of hormones/peptides – too many to list but the main ones are histamine (particularly foregut), tachykinins (Substance P), bradykinins, prostaglandins …….. and I’m sure serotonin’s in there too!  It does, however, appear to be massively guilty in causing carcinoid syndrome diarrhoea, desmoplasia, and carcinoid heart issues.

Where does Serotonin come from?

Serotonin’s technical name is 5-hydroxyltryptamine (5-HT).  It is converted from 5-Hydrotryptophan (5-HTP) which is also known as oxitriptan. 5-HTP is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of serotonin (…..and melatonin) from tryptophan. Tryptophan is interesting as that brings in one of the missing pieces of the jigsaw – food!  Tryptophan cannot be manufactured in the body, it must be brought in via diet. There is no serotonin in food, it is only manufactured in the body.

Tryptophan in food enters the body and serotonin is created by a biochemical conversion process which combines tryptophan (essentially a protein) with tryptophan hydroxylase (TPH), a chemical reactor. I suspect other substances might be involved in that process.  There are two forms of tryptophan hydroxylase – TPH1 and TPH2, which are encoded on two independent genes. TPH1 is linked to peripheral serotonin while TPH2 is related to brain serotonin.

While serotonin cannot cross the blood-brain barrier, tryptophan can, and once there, almost all of it is converted to serotonin. Unlike, peripheral setotonin where only a small percentage is used to generate serotonin. Just to emphasise that NET dietitians do not say to avoid foods containing tryptophan other than at the time of marker testing (see below and nutrition Blog 4). When you look at the role in brain serotonin, this might have an adverse effect. 

Are you happy with your serotonin?

Serotonin Inhibitors

The introduction of Somatostatin analogues (SSAs) such as Octreotide and Lanreotide, help reduce the secretion of “tumour-derived serotonin”  by binding to its receptors on the outside of the cell.  If you ever wondered why receptors are important, please check out my blog on this subject (click here).

I mentioned tryptophan hydroxylase (TPH) above and that is actually very interesting as this is how Telotristat Ethyl (XERMELO) is able to help with the symptoms of Carcinoid Syndrome diarrhea (not adequately controlled by SSAs) or where patients are unable to be treated by somatostatin analogues for whatever reason. It’s a potent inhibitor of TPH which will disrupt the manufacturing of tumour-derived serotonin. There is also evidence that it can help reduce the effects or halt the growth of the fibrosis leading to carcinoid heart disease.  Slight digression but useful to aid/enhance understanding at this point.  Read about Telotristat Ethyl here.

Serotonin and the Brain

There is constant discussion and assumption that serotonin-producing tumours are somehow causing depression, anxiety and rage.  Not as simple as that, it’s way more complicated.  Certain NETs can overproduce serotonin in the gut but the issues concerning depression and anxiety are normally associated with low levels of serotonin in the brain.

“Cancer anger” is a normal response to fear, despair and grief – a range of feelings which cancer brings into our lives. It can show as frustration, irritability, emotional withdrawal or aggression. You can feel it whether you have been diagnosed or you are a relative or friend. Cancer anger can happen at any stage of the illness, even years after treatment. I know that many people with cancer suffer from depression, anxiety and anger but they do not all have serotonin-producing tumours.  What they do have is a life threatening and/or life changing condition which is bound to have an effect on mind as well as body.  Hormones including Serotonin are natural substances found in the body and not just there to service NETs.

Serotonin is separately manufactured in the brain (~10%) and in the gastrointestinal tract (~90%).  The serotonin in the brain must be manufactured in the brain, it cannot be directly increased or reduced external to the brain, i.e. it cannot be directly reinforced by gut serotonin (peripheral serotonin). It follows that ‘brain serotonin’ and ‘gut serotonin’ are held in separate stores, they are manufactured in those stores and remain in those stores – there is no cross-pollination. This is managed by something called the blood-brain-barrier (BBB). Therefore, excess serotonin from NETs does not infiltrate the brain. As low-level of ‘brain serotonin’ is often linked to depression, it also follows that it’s possible to have high levels of serotonin in the gut but low levels in the brain.

My simple way of thinking about such things as outlined above, is that low levels of tryptophan in the brain might be contributing to low levels of serotonin in the brain.  To clarify that, I researched the reasons why there could be low serotonin in the brain. First, let’s dismiss any connection that the type of anti-depressant called Selective serotonin reuptake inhibitors (SSRIs) is involved. It’s thought that SSRIs work by increasing serotonin levels in the brain. Serotonin is a neurotransmitter (a messenger chemical that carries signals between nerve cells in the brain). We already discussed that it’s thought to have a good influence on mood, emotion and sleep. After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as “reuptake”). SSRIs work by blocking (“inhibiting”) reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells. So tryptophan or peripheral serotonin are not really involved.

It would be too simplistic to say that depression and related mental health conditions are caused by low serotonin levels (in the brain), but a rise in serotonin levels (in the brain) can improve symptoms and make people more responsive to other types of treatment, such as Cognitive Behaviour Therapy (CBT).  It’s also too simple to suggest that NET patients get depression and anxiety due to all the “hormones” these tumours produce.  Of course hormones can be involved in depression and anxiety but hormones aren’t their just for NET patients.  Cancer patients without hormone secreting tumours also get anxiety and depression so it’s possible that NET patients can get depression and anxiety in the same way.

It should also be noted that the precursor to serotonin, tryptophan, does pass through the BBB and it is therefore possible that tryptophan depletion can lead to less availability in the brain for the manufacture of brain serotonin.  Tryptophan depletion can be caused by dietary restrictions (i.e. lack of tryptophan foods) and also by the effects of certain types of tumours as excess serotonin is made leading to less availability of tryptophan.  Both could lead to low serotonin in the brain as less tryptophan gets there. It follows that foods containing tryptophan remain important in order to help maintain normal brain serotonin levels.

Measuring Serotonin levels

Measuring levels of serotonin is important in both diagnosis and management of certain NETs – although it’s probably sensible to test all potential NET patients during diagnosis when the type of tumour is not yet known.  Testing for tumour markers will differ between countries and within countries but the most common standard for testing Serotonin appears to be 5-HIAA (5-hydroxyindoleacetic acid) either via a 24-hour urine test or via a plasma version (mainly used in USA but now creeping into UK).  5-HIAA is the output (metabolite) of 5-HT (Serotonin). Not to be confused with the less reliable ‘serum serotonin’ which is a different test.

Another frequently asked question about serotonin tests is whether they are testing the amount in the brain or the gut. The answer is …… they are testing the levels in the blood. Furthermore, if you are measuring serotonin as an indicator for Carcinoid Syndrome, it has to be remembered that the majority of serotonin is in the gut, so even if serotonin levels in the brain were being measured alongside the gut levels, I don’t believe it would  influence the result in any significant way (but I have no science to back that up). It also has to be remembered that serum serotonin and 5HIAA are not absolute tests, they are not 100% sensitive, they are simply indicators of a potential problem. There are methods of measuring brain serotonin but it is very complex and beyond the purposes of this article.  However, I would just add that it is the reuptake of Serotonin in the brain (plus some other stuff) that can cause depression, not the actual level or amount in the brain.

I intentionally did not mention the other common test (Chromogranin A) or other markers as they are measuring different things but you can read about in my Testing for Markers blog.

Serotonin Video with myself and Dr Mike Morse

I made a video in 2019 with Dr Mike Morse sponsored by Lexicon Pharmaceuticals, Inc.  It’s all about Carcinoid Syndrome with a slant towards hormones, in particular Serotonin. Entitled “Likely Suspects: How Hormones May Lead to Carcinoid Syndrome – What People Living With Carcinoid Syndrome Need to Know”

You need to register to watch although some of you will already be registered and just need an email to login to see the this webcast. The one I’m featured in is the latest in a series on the subject and I’d like to break the record for views please! Please help me achieve this 💙 I would also love to get your feedback and sincerely hope you will find the time to listen in.  Please also find the time to complete the survey at the end.  Thanks

Click on the link here: www.CarcinoidWebcast.com

Don’t forget to press the play button and ensure your sound is turned up, particularly on mobile devices.

webcast morse allan

Summary

I did say it was a difficult jigsaw!

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Read my Cure Magazine contributions

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included

Please Share this post

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