Wednesday, May 27, 2015

Hypothyroidism Misdiagnosed as Depression
So we have an interesting medical conundrum, do we not? On one hand, doctors are more than eager to prescribe antidepressants at the drop of a hat, based entirely on the patients reported symptoms. No need for any blood tests, and no evidence that they work for the vast majority of people.  --Dr. Malcom Kendrick
"Treating Thyroid patients like children" by Dr. Malcolm Kendrick


Here is an imagined, but not far off the truth, conversation between a doctor and a patient.

‘Why can’t I have T3 doctor? I feel so much better when I do?’
‘Because I say so, now go away.’

Nowadays doctors, at least when they are in training, are repeatedly told that they must NEVER be paternalistic. To do so will result in immediate censure. In the UK it is also a very rapid way of failing the GP entrance exams. We are told that we must explore the patients’ expectations, listen to their worries and fears, and work with them in partnership to lead to a therapeutic partnership…. or some such left wing bollocks. [Joke]
How exactly that fits within the National Institute of Health and Care Excellence (NICE) guidelines is up for grabs. For those who don’t know, NICE decide on which drugs and interventions can be prescribed, or paid for, within the NHS. So you can explore expectations with your patient till the cows come home, only to find that you cannot prescribe what the patient wants, even requires. Even if it makes them feel much better and costs very little. Would you call this paternalism? Oxford entrance exam, discuss.

Don’t get me wrong, I think rationing is increasingly vital for healthcare provision, and at one point I supported NICE. I now realise how naïve and misguided I was…but that is a discussion for another day.

Where was I? Oh yes, T3. Most people have never heard of it. But I am willing to bet that if youhave heard of it, and you are a patient, you will certainly know all about this particular hormone. You will definitely know about a thousand times as much as your GP, who may nod sagely when you mention T3. But frankly they are unlikely to have any idea what it is, or does.

To be honest, until about a year ago I had no real idea what T3 was either, but I have learned quite a lot since. Wikipedia states that: ‘The thyroid hormones, triiodothyronine (T3) and its prohormone, thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism.’ I would like to draw your attention to the fact that, in Wikipedia, at least, T3 is mentioned before T4 – which makes it more important?

In reality, in a physiological sense at least, T4 comes before T3, in that T4 is produced almost exclusively by the thyroid gland in a ratio of about 17:1 T4 to T3. Once inside various tissues and organs T4 is then converted to T3, where it becomes the biologically active hormone.

Whichever does come first, it can be argued that T3 that is the key thyroid hormone, because T4 is basically a ‘prohormone.’ From Wikipedia again: ‘A prohormone refers to a committed precursor of a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. Though not hormones themselves, prohormones amplify the effects of existing hormones.’ Although the figures are not absolutely clear cut, it is usually stated that T3 is five times more biologically active than T4.

Therefore, if someone is hypothyroid, which is normally taken to mean that the thyroid gland is not producing a sufficient quantity of thyroid hormone, you would want to prescribe the active hormone T3, would you not?

This is a rather rhetorical question because what doctors do, at least since the 1960s, is to prescribe synthetic T4 (levothyroxine). Once T4 is in the body it is converted to T3 (through the kidneys, liver, spleen and brain – and numerous other thyroid hormone receptors throughout the body) and does its thing. In most cases this is a perfectly good treatment. However, there is a kicker, which I will get to.

At this point I feel I need to add that hypothyroidism is a very, very common condition. By the age of 60, 10% of people have ‘lab’ test abnormalities that would define them as having subclinical hypothyroidism. At least 2% of the population has overt, clinical, symptoms. Which means that we are talking about millions of people in the UK, possibly tens of millions in the EU and US.[It affects women ten times as much as men].

TSH
I now need to bring in another player called Thyroid Stimulating Hormone (TSH). As with all systems in the human body, a negative feedback loop controls the function of the thyroid gland, and it works something like this:

If you have a high T4 level, this is detected by the pituitary gland, which sits deep within your brain. At which point the pituitary gland reduces the production of Thyroid Stimulating Hormone. As TSH is the hormone that instructs the thyroid gland to produce T4/T3, production of T4/T3 falls. [There are actually a couple of other steps, but this is essentially what happens].

If T4 falls too far, the pituitary gland swings into action to produce more TSH. In turn stimulating the thyroid gland to manufacture more T4…and so it goes. Up and down, up and down, up and down. Endlessly until, of course, you get too old and drop dead. And there ain’t no feedback loop for that.

TSH is also important in that it is usually the substance you measure to decide whether or not someone is hypothyroid. If TSH is very high this means it is trying to ‘drive’ the thyroid gland into action – and failing. You also use the TSH level to determine the dose of T4 that is required as replacement therapy. If the level of TSH is low, this suggests you may be giving too much T4. If the level of TSH is high, this suggests you may be giving too little.

As you may have noticed, at this point I have slipped into talking about TSH and T4, with T3 getting very little mention. That is because this is where the medical profession now stands. Hypothyroidism means high TSH and low T4. You are getting adequate thyroid replacement hormone if TSH in the ‘normal’ range. End of.

Here is what the Royal College of Physicians (RCP) and the British Thyroid Association (BTA) have to say on the matter. Key points only
  • The only validated method of testing thyroid function is on blood, which must include serum TSH and a measure of free thyroxine (T4).
  • Overwhelming evidence supports the use of Thyroxine (T4) alone in the treatment of hypothyroidism. Thyroxine is usually prescribed as levothyroxine. We do not recommend the prescribing of additional Tri-iodothyronine (T3) in any presently available formulation, including Armour thyroid, as it is inconsistent with normal physiology, has not been scientifically proven to be of any benefit to patients, and may be harmful. [Then again, it may not be – harmful, that is]
An aside – (Additional information, as provided to me)
I should mention here that I have been told that the RCP has been asked on numerous occasions to cite references to research/studies showing “overwhelming evidence supports the use of thyroxine (T4 alone)”, but to date, they have provided none. A Freedom of Information (FOI) request that the RCP provide such evidence – again met with no response. A request was made via the ‘Ask for Evidence’ website, run in association with ‘Sense About Science’ asking for evidence on the safety and efficacy of L-T4 as a treatment for hypothyroidism. This request was directed to the RCP who eventually responded stating “The RCP’s guidance is based on the opinion of an expert panel which was temporarily formed for this purpose. The evidence they used to form their individual opinions has not been collated and therefore the RCP cannot provide any evidence list”1 (Jollyas they say, good)

Restricting the diagnosis and treatment of hypothyroidism to measuring T4 and TSH, and nothing else, is the approach that seems to be used by conventional medicine in the rest of the World. I recently received an e-mail from someone in Singapore telling me that their doctor was about to be struck off for prescribing T3 to patients- against Singaporean medical rules. In the UK, T3 testing is virtually banned, and the medical authorities are making it virtually impossible to prescribe T3 in any form.

In the UK, a doctor called Gordon Skinner was repeatedly dragged in front of the General Medical Council (GMC) for prescribing thyroxine to patients whose T4 and TSH levels were in the ‘normal range’. He was also attacked for prescribing natural thyroid extract (NDT) (a combination of T4 and T3) to his patients – who he felt would benefit. He is now dead. It has been suggested that constant and repeated efforts to strike him off the medical register may have had an impact on his health. I couldn’t possibly say.

Now, there is no doubt that this area is highly complex and for those who know this area, you will be aware that I am keeping things as simple as possible. But I think it is important to make a few points:
The lab tests, especially for TSH, are far from 100% reliable, to say the very least. In fact the man who developed the test in the UK, at Amersham International in Wales, has told me that the test is virtually worthless in many cases (especially continuous testing when patients are taking thyroid hormone replacement).

The conversion of T4 into T3 can be significantly reduced in some people. So these individuals can have normal T4 and TSH, but they are still effectively hypothyroid. For those who are interested in a bit more detail, there is a population with a defective DIO2 gene. This blocks T4 to T3 conversion, and results (amongst other things) in reduced T3 levels in the brain, which can lead to mood disorders2. I mention this single example to make it clear that there is solid scientific evidence to back up the conjecture that it is possible to be functionally ‘hypothyroid’ with normal blood tests.

A lot of people have reported significant improvements in their health through taking thyroxine, with normal blood tests, and also natural thyroid extract when their laboratory tests were ‘normal’. Please look at this article in the Daily Telegraph3…then look at the comments section – which is very, very telling. A cry of despair!

I am not going into further detail of how T4 binding and conversion in various organs can be affected by stress hormones, inflammation, trauma, adrenal insufficiency, lack of converting enzymes in tissues, and infection of various sorts. I shall just keep this simple by stating that it is possible to have enough T4, even T3 in your bloodstream, but these hormones have reduced ‘bioavailability’. This is not crank ‘woowoo’ stuff. This is real and measurable and you can find studies on this in peer-reviewed medical journals.

Far more telling, from my point of view, is the fact that hundreds, indeed thousands of patients report that, although their blood tests were normal, they felt terrible, and that they have felt so much better when they have been given ‘excess’ T4 and/T3, or NDT (natural desiccated thyroid). Whilst there is no doubt that some of them are, to quote a medical colleague, ‘not tightly wrapped.’ I have spoken to many, many, people who are calm, rational and reasonable, and their stories are compelling. A hellish existence that was ‘cured’ by Dr Skinner and his like. I refuse to believe that all of these patients are ‘somatising’ fruitcakes.

Comparing the use of SSRIs and ‘Unconventional’ Treatments for Hypothyroidism
At this point I will change tack slightly. For I think it is fascinating to compare and contrast the treatment of depression using SSRIs, with hypothyroid patients who complain that they are unwell, despite ‘normal’ T4 and TSH tests.

Today, almost all doctors you speak to believe that depression is due to a low level of serotonin in the brain. This is why they prescribe SSRIs (Selective Serotonin Reuptake Inhibitors) by the lorry-load. Drugs such as Prozac, Zoloft, Paxil etc.To quote from a recent article in the BMJ ‘Serotonin and depression, the marketing of a myth’4.

‘…the number of antidepressant prescriptions a year is slightly more than the number of people in the Western World.’

This all happens despite the fact that:
‘There was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew if SSRIs raised or lowered; they still don’t know. There was no evidence that treatment corrected anything.’

In short, with depression, there is no lab test, no way of measuring the impact of anti-depressants. They are prescribed purely and simply on the basis of the patient history. Equally, there is no doubt at all that SSRIs have significant side-effects, some of which are very, very serious e.g. increased suicidal tendency. They are also addictive and patients can end up stuck on them for years. So, they do cause harm.

Equally, as you may be aware, clinical trial data in this area have been horribly distorted….
“…That said, the fact that the class of antidepressants known as the selective serotonin reuptake inhibitors (SSRIs), are basically useless in treating depression in children and adults is not news to the FDA. Back on September 23, 2004, during testimony at a hearing before the House Oversight and Investigations Committee on Energy and Commerce, Dr Robert Temple, the FDA’s Director of the Office of Medical Policy, discussed the agency’s review on the efficacy of SSRIs with the children.”
He noted that it was important in a risk-benefit equation to understand the benefit side. “Of the seven products studied in pediatric MDD (Prozac, Zoloft, Paxil, Celexa, Effexor, Serzone and Remeron),” he testified, “FDA’s reviews of the effectiveness data resulted in only one approval (Prozac) for pediatric MDD.”

Overall,” Dr Temple said, “the efficacy results from 15 studies in pediatric MDD do not support the effectiveness of these drugs in pediatric populations.”

Also in 2004, a study of previously hidden unpublished data as well as published studies on five SSRIs, was conducted by Tim Kendall, deputy director of the Royal College of Psychiatrists’ Research Unit in London, to help analyze research to draw up the clinical guidelines for British regulators, and published in the Lancet.

Following his evaluation, Mr Kendall stated: “This data confirms what we found in adults with mild to moderate depression: SSRIs are no better than placebo, and there is no point in using something that increases the risk of suicide.”

In 2005, the British Medical Journal published another study that concluded that SSRIs are no more effective than a placebo and do not reduce depression.

In December 2006, at the most recent FDA advisory committee meeting held to review studies on SSRI use with adults, SSRI expert, Dr David Healy, author of, “The Antidepressant Era,” told the panel that the efficacy of SSRIs has been greatly exaggerated, while the actual studies reveal that only one in ten patients responds specifically to an SSRI rather than a nonspecific factor or placebo.

In February 2008, Irving Kirsch’s study at the Department of Psychology at the University of Hull is the first to examine both published and unpublished evidence of the effectiveness of selective serotonin reuptake inhibitors (SSRIs), which account for 16 million NHS prescriptions a year. The largest study of its kind concluded that antidepressant drugs do not work. More than £291 million was spent on antidepressants in 2006, including nearly £120 million on SSRIs. 4

Critics complain that industry funded studies are presented in ways to exaggerate benefits and obscure side effects. “These include failure to publish negative results, the use of multiple outcome measures, and selective presentation of ones that are positive, multiple publication of positive study results, and the exclusion of subjects from the analysis,” according to the paper, “Is Psychiatry For Sale,” by Joanna Moncrieff, in People’s Voice.”5

So we have an interesting medical conundrum, do we not? On one hand, doctors are more than eager to prescribe antidepressants at the drop of a hat, based entirely on the patients reported symptoms. No need for any blood tests, and no evidence that they work for the vast majority of people.

On the other hand, if a patient dares to say that they feel better taking T4 when their blood tests are normal, or if they say they feel better taking a combination of T3 and T4/NDT, they are dismissed as ‘somatising.’ Which is a posh medical way of saying, you are making your symptoms up and we don’t believe you. Equally, if a patient complains of continuing symptoms and that they don’t feel better when they are taking T4 (or T3 and T4) and their blood test results show ‘normal’ they are again accused of ‘somatising’6

The world, my friends, has gone nuts and, in a bitter irony, the medical profession – at least in this area – has become institutionally paternalistic. ‘You cannot be feeling better, because your blood tests say you were never unwell. So you cannot have treatment. And you, Dr Skinner and your like. If you dare treat patient’ symptoms you will be attacked and struck off from medical practice.’ Now I have looked long and hard, and I have found no evidence, from anywhere, that giving T3, in the dose that’s needed, causes any significant medical problems, and I have listened to repeated testimony from people who feel they have greatly improved.

As for antidepressants, these mostly useless addictive drugs that can increase suicide risk. ‘Have as many as you like for as long as you like. Because we fully believe everything you say about your symptoms….’ No need for any silly tests, or anything like that.

Compare and contrast, then try to make some sense of the medical world that we now live in.
Sigh.

P.S. Because I am considered to have alternative views about medical matters, many people contact me to help promote their ‘alternative’ ideas. Some I believe to be completely whacko, I smile sweetly and move on. Some I cannot decide. Other issues, once I start looking into the evidence, I find the evidence compelling.

I certainly find the evidence that a large number of people are effectively hypothyroid, with ‘normal’ thyroid blood tests, to be virtually overwhelming. Both from a scientific/physiology basis, and also from a patient testimonial basis.

I now firmly believe that the medical profession is currently doing these people a great disservice, and that the guidelines on the treatment of ‘hypothyroidism’ are rigid, autocratic, and just plain wrong (for a significant minority).

As with all medical matters that I write about, I have no axe to grind, no horse in the race, no financial links to anyone or anything with regard to treating thyroid patients. I simply hope this article can have some positive impact. For it seems very clear to me that many thousands, hundreds of thousands, of people are suffering unnecessarily. And I would like it to stop.

References:
2.   “Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine Plus Triiodothyronine Therapy in Hypothyroid Patients”http://press.endocrine.org/doi/pdf/10.1210/jc.2008-1301
4.   Serotonin and Depression, the marketing of a myth.’ BMJ2015;350:h1771
5.   Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. “Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration.” 2008, PLoS Med 5(2): e45 doi:10.1371/journal.pmed.0050045: Access full article at http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045
7.   Professor A Weetman – http://www.medscape.com/viewarticle/524955

Further postscript
Malcolm – we need to clear up the fact regarding the definition of ‘hypothyroidism’ which is “underactivity of the thyroid gland” according to the RCP Policy Statement on the diagnosis and management of hypothyroidism. Hypothyroidism is easily diagnosed and more often than not, easily treated with L-thyroxine only. However, what is being missed by everybody is that over 300,000 UK citizens (15% of the thyroid community – millions worldwide) have a normally functioning thyroid GLAND, but the hormone it is secreting is not getting into the cells where it does its work. These are the folk who need T3, in combo. with T4, T3 alone or in NDT. The RCP teaching curriculum makes no mention of the possibility of a non-thyroidal condition where patients suffer the same symptoms and signs of hypothyroidism that may need to be treated with a different medication or hormone. When these patients complain of continuing symptoms when treated with L-T4 monotherapy, many are given an incorrect diagnosis of ME, CFS, FM, depression, functional somatoform disorder – or even old age blah, blah, blah – and sent on their way without further investigation or treatment. This is a serious business, which the RCP and BTA choose to ignore.
This entry was posted in Dr Malcolm Kendrick on May 1, 2015.


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