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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Neuroendocrine Tumours: a spotlight on Pheochromocytomas and Paragangliomas

spotlight on pheo para

I spend a lot of time talking about the most common forms of Neuroendocrine Tumours (NETs), but what about the less well-known types?  As part of my commitment to all types of NETs, I’d like to shine a light on two less common tumour types known as Pheochromocytomas and Paragangliomas – incidence rate approximately 8 per million per year. They are normally grouped together and the definitions below will confirm why.  If you think it’s difficult to diagnose a mainstream NET, this particular sub-type is a real challenge.

So, let’s get definitions out of the way:

Pheochromocytomas (Pheo for short)

Pheochromocytomas are tumours of the adrenal gland that produce excess adrenaline. They arise from the central portion of the adrenal gland, which is called the adrenal medulla (the remainder of the gland is known as the cortex which performs a different role and can be associated with a different tumour type). The adrenal medulla is responsible for the normal production of adrenaline, which our body requires to help maintain blood pressure and to help cope with stressful situations.  The adrenal glands are situated on top of the kidneys (i.e. there are two). Adrenaline is also called ‘epinephrine’ which is curiously one of the 5 E’s of Carcinoid Syndrome.

Paragangliomas (Para for short)

Paragangliomas are tumours that grow in cells of the ‘peripheral’ nervous system (i.e. the nerves outside the brain and spinal cord). Like Pheochromocytomas, they can release excess adrenaline.  There can be confusion between the two types of tumour as Paragangliomas are often described as extra-adrenal Pheochromocytomas (i.e. a Pheo external to the adrenal gland).

Going forward, I’m going to talk about both using the single term of ‘Pheochromocytoma’ in the context of an adrenaline secreting tumour but may refer to Paraganglioma where there might be a difference other than anatomical location.

Pheochromocytomas are often referred to as the “ten percent tumour” because as a rule of thumb they do many things about ten percent of the time. However, these figures are slowly changing, so this label is gradually becoming less apparent. The following is a fairly exhaustive list of these characteristics:

A few facts about Pheochromocytomas

  • As much as 1 in 3 are Malignant but most have undetermined biologic potential.  A recent document issued by the World Health Organisation (WHO) stated that “Paragangliomas should not be termed benign”.
  • Around 10% of Pheochromocytomas are Bilateral (i.e. found in both adrenal glands: 90% arise in just one of the two adrenal glands)
  • Around 10% are Extra-Adrenal (found within nervous tissue outside of the adrenal glands … i.e. 10% are Paragangliomas)
  • Around 10% are found in Children (i.e. 90% in adults)
  • Up to 30% are Familial potentially rising to 50% for metastatic cases and Multiple Endocrine Neoplasia (MEN) involvement.
  • The recurrence rate is around 16%, i.e. about 1 in 6 patients have a tumor that comes back after surgery.  Tumors that come back also have the potential to be malignant. If you have pheo or para and have surgery to remove it, be sure to continue to check in with your doctor to monitor for any returning tumors.
  • Present with a stroke (10% of these tumours are found after the patient has a stroke)

Symptoms

The classic symptoms of Pheochromocytomas are those attributable to excess adrenaline production. Often these patients will have recurring episodes of sweating, headache, and a feeling of high anxiety.

  • Headaches (severe)(one of the classic triad, see below)
  • Excess sweating (generalized)(one of the classic triad, see below)
  • Racing heart (tachycardia and palpitations)(one of the classic triad, see below)
  • Anxiety and nervousness
  • Hypertension
  • Nervous shaking (tremors)
  • Pain in the lower chest or upper abdomen
  • Nausea (with or without vomiting)
  • Weight loss
  • Heat intolerance

Diagnosing Pheochromocytomas

According to the ISI Book on NETs (Woltering, Vinik, O’Dorisio, et al), Pheochromocytomas present with a classic triad of symptoms and signs:  headache, palpitations and sweating.  This symptom complex has a high specificity and sensitivity (>90%) for the diagnosis of Pheochromocytomas.  The figure is much lower in individual symptom presentations (palpitations 50%, sweating 30%, headaches 20%). In addition to correctly diagnosing from these symptoms, Pheochromocytomas may also be found incidentally during a surgical procedure even after a diagnosis of an ‘adrenal incidentaloma’

Markers.  Like serotonin secreting tumours, adrenal secreting tumours convert the offending hormone into something which comes out in urine. In fact, this is measured by 24 hour urine test very similar to 5HIAA (with its own diet and drug restrictions).  It’s known as 24-hour urinary catacholamines and metanephrines. This test is designed to measure production of the different types of adrenaline compounds that the adrenal glands make. Since the body gets rid of these hormones in the urine, we simply collect a patient’s urine for 24 hours to determine if they are over-produced.  Like 5HIAA, there is also a plasma (blood draw) version of the test.  According to the ISI Book on NETs, there is also an additional test called ‘Vanillylmandelic Acid (VMA).  This reference also indicates the most sensitive test is plasma free total metanephrines. Also read more here.

Genetics.  The familial connection with Pheo/Para is complex. Up to 13 genes have been identified including NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2(SDH5), TMEM127, MAXm EPAS1, FH, MDH2.  Read more here ( recent update)The NIH also have a useful section –click here.

Scans.  Other than the usual range of scanners, ultrasound, CT/MRI, all of which may be used to find evidence of something, the other scan of note is called MIBG.  This is a nuclear scan similar in concept to the Octreotide Scan given to many NET patients (in fact some Pheo patients my get an Octreotide scan if they have somatostatin receptors).  The key differences with MIBG is the liquid radioactive material mix which is called iodine-123-meta-iodobenzylguanidine or 131-meta-iodobenzylguanidine  (this is where the acronym MIBG originates).  Together with the markers above, the results will drive treatment.  Depending on availability, the latest PET scans may also be available potentially offering greater detail and accuracy i.e. 18F-FDOPA, 18F-FDG and Ga68.  Read more on scans here.

This statement and diagram was provided by Dr Mark Lewis who is an Oncologist and MEN patient.  “The algorithm for working up a hyperadrenergic state is attached (and was developed by Dr. Young at Mayo Clinic). It outlines the most reliable testing for a pheo or Paraganglioma”

work-up-for-diagnosing-pheo

Additional Factors and Considerations

  1. This is an awareness post so I’m not covering treatment options in any detail except to say that surgery if often used to remove as much tumour as possible.   Somatostatin Analogues may also be used in certain scenarios in addition to other hormone suppression or symptom controlling drugs. That said, Pheo/Para patients may be interested in a PRRT trial exclusively for Pheo/Para – read more here (see section entitled – “What about Pheo/Para”)
  2. The adrenal cortex mentioned above is actually the site for Adrenocortical Carcinoma (ACC) – this is a totally different cancer.
  3. Pheochromocytomas are probably difficult to diagnose (you only have to look at the symptoms to see that).  The differential diagnoses (i.e. potential misdiagnoses) are: hyperthyroidism, hypoglycaemia, mastocytosis, carcinoid syndrome, menopause, heart failure, arrhythmias, migraine, epilepsy, porphyria lead poisoning, panic attacks and fictitious disorders such as the use of cocaine and benzedrine.
  4. Many Pheochromocytoma patients will also be affected by Multiple Endocrine Neoplasia (MEN), in particular MEN2 (there are some wide-ranging percentage figures online for this aspect).  There can also be an association with Von Hippel-Lindau (VHL) syndrome and less commonly with Neurofibromatosis type 1.
  5. Given the nature of the hormones involved with Pheochromocytomas, there is a risk of intraoperative hypertensive crises. This is similar in some ways to Carcinoid Crisis but needs careful consideration by those involved in any invasive procedure.

Newly Approved Drug – AZEDRA

On 30th July 2018, Progenics Pharmaceuticals Announces FDA Approval for AZEDRA® (iobenguane I 131) to Treat Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma – read more by clicking here.

Summary

Pheochromocytomas are very complex involving many of the challenges found in the more abundant and common types of NETs.  To underscore this statement, please see this case study where one patient was misdiagnosed with psychiatric problems for 13 years before being correctly diagnosed with a metastatic Pheochromocytoma.

Also  ….. take a look at this awareness video produced by the Pheo Para Alliance. I voted this as the best piece of NET awareness in 2017. click here to watch

This is an extremely basic overview offered as an awareness message about the lesser known types of NETs.  I refer you to my disclaimer.  If you wish to learn more about Pheochromocytomas and Paragangliomas, check out the links below.

Research References used in this post:

Know Pheo/Para from Progenics Pharma

ISI – Neuroendocrine Tumors 2016

http://pheopara.org/ (in August 2017, the Pheo Para Troopers and the Pheo Para Project Merged)

http://www.pheosupportfoundation.org/

http://www.pheochromocytoma.org/

http://endocrinediseases.org/

https://www.endocrineweb.com/

Various authoritative Neuroendocrine and Endocrine Sites.

Also ……why not take a look at these Pheo boggers:

  1. Kirsty Dalglishhttps://kirstywestwood.wordpress.com/
  2. to follow

 

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!

Ronny Allan is an award winning patient leader and advocate for Neuroendocrine Cancer.