Published in InterAction 46, Autumn 2003
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Dear Doctor: Thyroid thoughts
Due to the overlap in symptoms, we often hear from people worried that they may have an underactive thyroid in addition to or instead of M.E. Here, Professor Tony Pinching outlines the mainstream view on testing and treating thyroid problems in CFS patients.
CFS/M.E. and hypothyroidism (reduced thyroid hormone production) are both relatively common conditions, and some of the symptoms are quite similar. Differentiating the two conditions or identifying their possible co-existence are common issues for patients and clinicians, in both diagnosis and treatment.
The situation is complicated by the fact that some unorthodox practitioners recommend the use of thyroid hormones in the treatment of CFS/M.E. Moreover, some people think that thyroid and some endocrine (hormone) abnormalities are relevant to the causation of CFS/M.E.
Symptoms in common
The body has a limited range of symptoms it can use to reveal any condition, so the lists of symptoms can all sound quite similar. However, closer examination often reveals important differences. Sometimes, tests for one or another condition can help clarify the matter, though any results must be interpreted in the context of the patient’s clinical history, symptoms and signs.
This is well illustrated in relation to hypothyroidism and CFS/M.E. because the characteristic features of fatigue in the two conditions actually manifest rather differently. For example, the delayed setbacks so often seem after extra activity in CFS/M.E. are uncommon in uncomplicated hypothyroidism.
An underactive thyroid is quite often associated with particular physical signs on examination (e.g. changes in skin, hair and tendon reflexes) that can indicate the diagnoses. Even so, it’s important after evaluation the patient to do tests on thyroid function in case of subtle or non-typical hypothyroidism.
Normal thyroid function and control
In order to understand these tests, and also thyroid treatment, we need to look at how the body works.
The thyroid gland in the neck produces hormones called thyroxine (T4) and tri-iodothyronine (T3), under the control of the thyroid stimulating hormone (TSH), which is produced in the pituitary gland just beneath the brain called the hypothalamus.
In controlling body metabolism, the functions of T4 and T3 overlap, with the main difference being in their rate of action. If for some reason the thyroid gland is producing less T4 and T3 than the body needs, this is detected by the hypothalamus and pituitary gland, and more TSH is produced to stimulate production of thyroid hormones of the body.
Similarly, if there is too much T4 and /or T3, TSH production will be reduced to lessen the thyroid gland’s production of these hormones. This is rather like the way a thermostat controls the heat production by the boiler in a central heating system to keep the house at the correct temperature.
Thyroid tests in clinical practice
Most laboratories will test T4, the main thyroid hormone, and TSH. Although it is possible to test for T3 as well, this is not usually necessary, as it typically reflects the changes in T4. The normal range of these hormones will be given, representing the values obtained in the great majority of people who are well. You could manage that the body metabolism of an athlete and a sedentary person would be different, so their hormone levels may reflect that, all within this ‘normal’ range.
If the thyroid gland is damaged, T4 and T3 will be reduced and TSH will be raised, as part of an attempt to increase thyroid hormone production. In practice the TSH is often the most informative and sensitive, so some laboratories use this on its own as a screening test. If the pituitary gland is not producing enough TSH, then both this and T4 will be reduced.
Causes of hypothyroidism
The main causes of an underactive thyroid are autoimmune damage (shown by the presence in blood tests of antibodies to the thyroid tissue), other types of damage to the thyroid gland (such as after surgery or infection of the thyroid), decreased function of the pituitary gland (less common) and iodine deficiency (now rare in UK).
Immune damage to the thyroid is more common in women and tends to run in families so there’s a greater chance of you having a thyroid problem if one of your parents did.
Treatment with thyroxine
If someone with thyroid disease is given hormone replacement therapy such as throxine, the TSH will fall to within the normal range once adequate amounts are given. Because this hormone acts quite slowly, levels are best tested about three months after any change in treatment, T3 acts a bit faster, but sudden changes are rarely needed in replacement treatment, and may be harder to regulate.
If too little thyroid hormone is given, the TSH will remain high; if too much, it will fall below the normal range, and may even be undetectable. This reflects the detection of so much thyroid hormone in the system that the hypothalamus/pituitary control mechanisms are trying to turn off thyroxine production. This is also seen in people whose thyroid is overactive and not responding to TSH control.
Interfaces between CFS/M.E. and thyroid disease
Hypothyroidism could be mistaken for CFS/M.E. or vice versa, though a careful clinical and laboratory assessment can usually resolve the matter.
However, the two conditions may co-exist. As both are quite common, this is probably coincidental in most cases. However, in a very small number of patients, anecdotes suggest that whatever triggered the CFS/M.E. may also have triggered the hypothyroidism, e.g. a viral infection that can also cause thyroiditis (inflammation of the thyroid gland).
Sometimes a person with CFS/M.E., early investigations reveal evidence of subtle hypothyroidism, which is then thought to explain the symptoms. However, when effective treatment of hypothyroidism is achieved, many symptoms remain. It may come to be recognised that these are due to CFS/M.E. and not thyroid disorder as first thought.
It is quite common that initially assuming the thyroid diagnosis to be correct, clinicians and patients try increasing the dose of thyroxine or even adding T3. Thyroid levels may get so high that the TSH is suppressed, and sometimes new symptoms of thyroid hormone excess are seen – but despite this, the original symptoms remain. Most of the patients who are referred to me from endocrinologists have been through this loop!
Even so, a patient with a diagnosis of CFS/M.E. may later develop thyroid disorder, and it is important to be alert to this. A change in the pattern or type of symptoms, a deterioration or unexpected failure to improve from a setback should always lead to re-evaluation and appropriate tests.
Treatment of thyroid disorder when it coexists with CFS/M.E. should be guided by those symptoms and physical signs that are particular to thyroid disease, and most importantly, by the TSH levels.
Effect of inappropriate supplementation
One of the problems in assessing the effects of treatment is that giving extra thyroid hormone may give a person, especially someone who is ill, a temporary sense of greater well-being. This can be misleading and due to ‘false’ energy or benefit.
As the body then goes on to suppress its own thyroid hormone production, the apparent improvement seems to wane after a few weeks or months. This may leave someone to increase the dose, and the same cycle occurs.
Eventually all the body’s own production would get shut down. This is just like the thermostat on your central heating system turning off the boiler if the sun is shining and the house is warm enough. The difference in the body is that, if it’s not being used, the thyroid gland will gradually atrophy (get smaller and lose thyroxine-producing cells).
If inappropriate thyroxine replacement is given to someone whose own thyroid production and regulation is in fact normal, the body will in time become entirely dependent upon external supply. This means that the subtle regulation of hormone production to the changing needs of the body’s functioning will be lost. It is unlikely that regular dosing of thyroxine by mouth can truly match this.
If the dosing were then to cease, it would take quite some time for the body’s own production to get up to normal levels again.
Some unorthodox practitioners think that giving extra thyroxine to CFS/M.E. patients can help and state that their own studies show reduced levels of thyroid hormone – although still within the normal ranges - in these patients. Their belief is that reduced hormone production is partly responsible for CFS/M.E. This view is not widely supported by endocrinologists or other CFS/M.E. physicians, who remain concerned about the detrimental long-term effects of this approach.
Instances of dramatic but sustained improvement, which are very infrequent but widely promulgated, probably represent treatment of previously undetected hypothyroidism. If there is a more substantial rationale for thyroid hormone use in the treatment of CFS/M.E. patients, more evidence is needed to justify it. (Note that in placebo-controlled trials, the use of thyroid hormone treatment for patients with suggestive symptoms but ‘normal’ blood test results for thyroid function has not shown any sustained beneficial effect on symptoms).
Adrenal thoughts too
Most of the same issues arise in respect of the adrenal corticosteroid hormones (cortisol), which are regulated by the pituitary hormone ACTH. The sense of well-being from supplemental treatment is more pronounced with these steroids; however so are the hazards of over-treatment in the long term, and of suddenly discontinuing such treatment.
One study did show minor benefit in treating CFS patients with prednisolone, while another one using different supplementation did not show benefit. Overall, the long-term adverse effects of steroid use appear to outweigh any possible benefit.
Most studies now strongly indicate that the changes in steroid production and control in CFS patients are secondary to the effects of the illness, rather than a cause.
Thyroid disease and CFS/M.E. are both quite common and have some similarities. Patients must be carefully evaluated clinically, and with suitable laboratory tests, to differentiate them or, if appropriate, to diagnose both in the same person and to treat them in parallel.
Overall, we should be extremely careful with the quite widely promoted suggestion that supplementary hormone treatment be given to patients with CFS/M.E. in the absence of evidence of endocrine disease.
Any trial of therapy must be carefully monitored clinically and in laboratory tests, with a clear prior agreement and understanding about the duration, monitoring, intended outcome and potential hazards. It is wise to seek another informed opinion before embarking on such a treatment.
If there are genuine concerns about subtle endocrine disease in patients with CFS/M.E., referral to an n endocrinologist for specialist assessment is recommended.
With thanks to consultant endocrinologist, Prof. Ashley Grossman
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