That's a mouthful of thyroid medicine, and it doesn't get any easier.
To be fair, it has got a lot easier over the course of my professional lifetime, but there is still a long way to go.
When all else fails, I frequently resort to the "suck it and see" approach of a trial of thyroid replacement therapy - details later.
This condition is generally left untreated by conventional thyroid medicine practitioners. Blood tests are checked periodically in case the output of the gland drops out of the reference range.
It is already causing elevated cholesterol and arterial stiffness, risk factors for later cardiovascular disease. The conventional definition includes "minimally symptomatic" as though mild symptoms are to be disregarded.
The boiled frog principle is an unpleasant analogy, but does drive home a point.
The story goes that if one puts a frog into boiling water it dies very unhappily and maybe noisily - but certainly with a lot of kicking.
If one put the frog into nice cool water and gradually heat it up to boiling, the poor frog dies without so much commotion. The heat crept up on it.
I haven't tried to confirm this.
Symptoms of low thyroid creep up on one - you never see them coming.
Thyroid medicine is sneaky.
Aches and pains are part of the story. A good list of other symptoms is on the
thyroid institute.org site
Our basal (early morning before stirring) temperature should be 36.7+/-0.2 degrees centigrade. Here it will be lower. There are special thermometers for measuring basal temperature.
TSH levels are commonly used. Thyroid stimulating hormone or thyrotrophin, is the pituitary derived hormone accelerator for our thyroid gland.
This is increased if the thyroid is having trouble doing its job, to give it a kick in the pants.
There are a number of problems with this test. The commonly accepted reference range of 0.5 to 4 is in dispute, and the test depends on having intact feedback control mechanisms.
Our brain measures the ambient temperature, the current blood levels of thyroid hormones and responds to other hormone and interleukin chemical messengers - lots of things can influence TSH.
Gut derived bacterial endotoxin binds to TSH receptors in our thyroid gland, blocking its effect - so the output from the gland no longer reflects only the TSH level.
This is the range of values assuming that one is just as likely to have above as below average levels, encompassing 95% of a healthy population's results.
Most people have results close to the average, and the further from here, the fewer results. This produces the "bell curve" distribution.
One problem is getting a truly healthy population to give one this reference range. Remember that boiled frog principle.
It has been pointed out that if people with a family history of thyroid disease and those with anti thyroid antibodies in their blood are excluded, the reference range becomes 0.5 to 2.5!
The other problem is the wide range of normal variation, even more so for T4 levels.
If someone has a level bang in the middle of the reference range, we are happier - but for all we know they may have been previously at one extreme of the range, and healthier for it.
TSH (accelerator) levels high in the reference range plus T4 (output) levels low in their respective range, is getting suspicious.
If you know or suspect that you have, make every effort to obtain the results.
Comparing current with previous results is very valuable. The position in the reference range should remain the same in health. If it has shifted a lot, a "normal" result may be shown to be quite the reverse.
If you have a thyroid test now, ensure you get a copy of the result, as you may shift residence or change doctors in the future.
Thyroxine (T4) is "long-lived and minimally active." It is basically a blood-born store of potential active thyroid hormone.
The activation of T4 involves removal of an iodine (deiodination,) catalysed by activating deiodinase (D2) enzyme. This enzyme is increased when supply of T4 from the thyroid gland is deficient, as the body attempts to cope.
There is also an inactivating deiodinase (D3) which can inactivate T4 and T3 by removing a different iodine atom.
These deiodinases control⁶ thyroid hormone action at the cellular level, relatively independently of thyroid hormone serum concentrations.
They are selenoproteins, with the rare amino acid selenocysteine in their structure.
The synthesis of selenoproteins is difficult to start with, and selenium deficiency isn't uncommon. This is just one more place where thyroid action can founder. People have been found with genetic defects of this as well.
There are multiple thyroid hormone transporters to get T4 and T3 into the cell in the first place, which are yet another place where things can go wrong.
Blood levels of thyroid hormones are definitely not the final arbiter.
This is the suck it and see method, which I believe should be more widely used.
Gelb advocated checking serum cholesterol and basal metabolic rate before and after a trial of thyroid hormone replacement. These fell and rose respectively, when a person had been hypothyroid before the trial.
My method is to take triiodothyronine 20 mcg. tablets over three or four days, using symptoms as the guide. This is much quicker⁴, but does have placebo response as a confounder.
We keep a bottle of these tablets and people take half a dozen for the test.
There are some circumstances where this sort of test is inappropriate, such as in people with angina or heart failure. It has to be prescribed and supervised by your doctor. If your doctor is happy to contact me I'll be very happy to discuss it with them.
On day 1, take one tablet in the morning. At the end of the day, take stock of how you have felt. Three possibilities are better, worse or no different.
Better might be more energy, an easier bowel action, not so cold or getting rid of a large amount of fluid (as urine.) Pain might not sound better, but ones' joint and back aches may be worse.
Aches and pains in hypothyroidism, commonly get worse when thyroid replacement is first started.
If this describes your experience, the test is now complete. You can use up remaining tablets at the dose of one per day.
Worse in this context is like a "cat on a hot tin roof." One might feel jittery and shaky, nervy and frightened or feel palpitations. The tablet will wear off, so just rest and wait.
Dispose of the remaining tablets safely.
The same means tomorrow take one in the morning and one at midday, then observe oneself as before.
If you are sure there is no effect whatsoever, increase to three and even four tablets, on successive days, until some positive or negative effect is felt.
Resting metabolic rate is probably the best, as this is an end result of thyroid hormone action.
Brachioradialis reflex timing is apparently well correlated with this.
This chap's ideas have come in for a lot of criticism, but I have a couple of patients who have fitted his description and responded exactly as he predicts.
The proposition is that we can be stuck producing inactive reverse T3 rather that active T3, and just need a little help to get back on track.
Advances in thyroid medicine can come from sources outside of conventional endocrinology.
Most people are offered synthetic thyroxine (T4,) and blood tests are done periodically to ensure the dose is correct.
My experience is that symptoms are more useful than test results now. If the TSH level is "normal" but the person still has their symptoms, they need more or different treatment!
I again often use a therapeutic trial, adding just one triiodothyronine (T3) 20mcg. tablet to their T4 for a day or two, to see if the person feels better.
The TSH level probably needs to be at or below the bottom of the range, and the T4 level at or just above the top of the range, for adequate replacement.
Mary Shomon is a very good resource for how to tackle this with your doctor, as she has been in the same position herself.
Helicobactor pylori gastritis may be responsible for an inadequate response to the treatment.
It can decrease absorption of oral thyroxine by decreasing gastric acid secretion⁵.
Sam Queen from the institute for health realities is concerned about this. He always wants to know why the body is running along with reduced thyroid function, in order to treat the underlying problem.
I am sure that he is correct in this concern. Thyroid medicine needs to be tackled holistically.
Treating thyroid with replacement is just like any suppression of symptoms. The underlying cause is not corrected, and in fact the body may have been better off with the reduced thyroid function.
This applies to borderline and very mild hypothyroidism, not severe.
Thyroid medicine may reflect disturbances in other areas of medicine.
The drug amiodorone, iodine containing contrast media used in radiology and kelp tablets, are common sources of large doses of iodine.
Excessive iodine inhibits the thyroid - too much of a good thing? Maybe, maybe not. Only 20% of iodine taken into your body, goes to the thyroid gland. Iodine has other functions, regarding oestrogen hormones, protecting our body from invading organisms and the various clock cycles in our chemistry.
Deficiency is no good either, results in poorly acting thyroid and goitre. Moderate iodine and so thyroid hormone deficiency during pregnancy and early childhood can result in cognitive deficit which can show up from 2 years age on.
Modern pollution with fluoride and bromide contributes to iodine deficiency, so it is very common.
Urine tests for iodine can tell if you're short of it. This is a very useful test in thyroid medicine.
Auto-antibodies show immune damage, which may be primary or secondary to toxin effects. There different opinions in thyroid medicine, about them reflecting current status as they wax and wane.
High levels of thyroperoxidase antibodies (microsomal antibodies) can interfere with T4 and T3 synthesis by inhibiting the enzymic combination of iodine with thyroglobulin, or simply by causing inflammation and destruction of the thyroid gland.
Less commonly, thyroglobulin autoantibodies can be seen. These are a marker of autoimmune disease in general. Thyroglobulin makes up most of the weight of the thyroid gland, waiting for iodine to combine with.
TSH receptor autoantibodies can be usefully measured if the cause of an overactive thyroid isn't found. They can stimulate the gland, causing Grave's disease and the bulging eyes that go with it.
LATS may be one of a number of different antibodies to the TSH receptor in Graves' disease.
You might think from the rest of this page that your thyroid can be considered as an isolated system.
Nothing in our body can be understood on that basis - everything is interconnected, not operating independently.
Adrenal hormone is needed for thyroid hormone to enter cells. Thyroid treatment will increase requirements for adrenal hormone.
This is very important in initial treatment of secondary hypothyroidism, when thyroid hormone could induce an adrenal crisis.
A very good site on thyroid medicine has a page on adrenal/thyroid gland testing, at... stopthethyroidmadness.com
Also worth a read. Sensible-alternative.com.au is a naturopathy site with a good thyroid medicine article.
A very good dissertation by a medical doctor is at http://thyroid-disease.org.uk Dr Barry J Durrant-Peatfield gives an excellent explanation of why and when and how adrenal hormone replacement therapy may be needed as well as thyroid.
Hormones are chemical messengers, on their way to someplace in our body, to do a job.
We are really only interested in how well the job is done.
This may depend on the concentration of the hormone there, and/or its rate of supply (as it may be used up in passing on its message.)
In the case of TSH, the receptor is largely expressed on the cell surface, but on addition of TSH, some of the receptors are rapidly internalized² (with the TSH attached.)
That is, the TSH is used up in the process of passing on its message.
There is a body of opinion which holds that T4 is an important way of delivering elemental iodine to peripheral tissues for purposes quite separate to the function of T3.
Measuring the blood concentration is an indirect measure of rate of supply, as demonstrated by the analogy of filling a leaky drum.
The drum has a crack down the side, and leaks. A constant level is maintained inside the drum, with fluid pouring in and out at the same rate.
Increasing the rate of supply, increases the fluid level in the drum until the rate of leakage again equals that of supply.
The level in the drum is like the blood concentration.
Except in otherwise healthy people who recently had surgical or radioactive iodine ablation, it is best to "start low and go slow."
This is especially so if someone has heart disease, as speeding up their heart may aggravate angina.
Most adults will end up on 100-200 micrograms, but if there is any concern it is best to start with 25mcg. for the first month, and increase by this amount this often.
If say, the best dose ends up being 800mcg. per week, this can be done by having 100mcg. 5 days and 150mcg. 2 days. It's long acting, so there's no need to cut tablets to have the same every day.
The time of day for taking the dose has been investigated³ and the usually prescribed morning dosing may not be best. This study found better blood levels with bedtime dosing. I wonder how often morning doses were quickly followed by breakfast.
Mrs L was a good example of how one needs to carefully titrate the dose. On 100mcg T4 daily she had "dry skin, constipation, hoarse on and off, feeling the cold, pulse 58/min and tiredness."
She felt better when 10mcg of T3 was added, so later she went onto 150mcg of T4 per day.
In a month on this she "lost 2 lb, and lost the feeling of her pulse thumping in her neck - generally better."
Uncommonly, hypothyroidism may be secondary to pituitary gland failure. TSH will be normal or low. This is still a big problem in countries with little advanced obstetric care, where blood loss can cause pituitary damage (Sheehan's syndrome.)
In a recent survey⁸ in Iceland (where care is good)
"Loss of lactation (n=6) and failure to resume menstruation (n=6) were the most common symptoms. All of the women had various unspecific symptoms such as lethargy, intolerance of cold, heat flushes, decreased libido, dry skin and mood changes. Some had diminished genital and axial hair."
Six of these seven women waited at least 8 months before diagnosed. They were the only seven diagnosed in 21 years. Uncommon conditions are not thought of readily.
This indicates that the thyroid gland has become autonomous,
producing excess thyroxine (T4) and/or the active tri-iodo thyronine
It has escaped from physiological control via the pituitary gland.
If one has weight loss, diarrhoea, shakes and nervousness, in thyroid medicine this is called clinical hyperthyroidism.
Subclinical hyperthyroidism is when the person is well despite the low TSH (below 0.44 mIU/L.) One expects the T4 and T3 levels to still be within the reference range.
A large thyroid medicine study has just been published⁷ confirming that this subclinical state still carries increased risk of atrial fibrillation and early death from multiple causes.
2. Singh SP, McDonald D, Hope TJ, Prabhakar BS Endocrinology. 2004 Feb;145(2):1003-10.
3. Nienke Bolk et al Effects of Evening vs Morning Levothyroxine Intake. A Randomized Double-blind Crossover trial
Arch Intern Med. 2010;170(22):1996-2003.
4. Mrs V was a good example. Her notes read...
"Felt better in approx. 1 hour of taking her (first) Tertroxin - noticed first by her husband. Lost 3kg in the following week. Feet and hands less puffy - generally better in herself, on 20mcg per day."
5. Bugdaci et al, The Role of Helicobacter pylori in Patients with Hypothyroidism in Whom Normal Thyrotropin Levels Could Not be Achieved Despite Treatment with High Doses of Thyroxine.
Helicobacter. 2011 Apr;16(2):124-30
6. http://edrv.endojournals.org/content/29/7/898.full This is a long and technical paper with a very good discussion at the start.
7. Subclinical Hyperthyroidism and the Risk of Coronary Heart Disease and Mortality. Tinh-Hai Collet et al.
Arch Intern Med. Published online April 23,2012
Another long and technical thyroid medicine paper, with good information at both ends.
Is there something else you would like to read about?
This search button will bring up anywhere on this site your words are mentioned...
Reduction in our blood level of T4 thyroid hormone especially, increases the pituitary gland secretion of TSH and increase in T4 level inhibits it.
The end products of thyroid function thus control it, called "feedback control."
Hyper is greater, hypo is lesser, hence over-active thyroid gland is called hyperthyroidism.
Atrial fibrillation is a condition when the atria of the heart, the chambers leading into the main pumping chambers, fail to contract rhythmically and just wriggle like a bag of worms.