THYROID FUNCTION IN ME
IS THERE A MAJOR DIAGNOSTIC
PROBLEM?
[Dr Betty Dowsett researched and wrote this article - May 2002
after receiving a letter from an ME patient who had suffered adrenal failure
following over-treatment with thyroid hormones. Ed.]
1. INTRODUCTION: It as been suggested that
'scandalous medical ignorance leading to an epidemic of undiagnosed thyroid
deficiency, underlies the increasing prevalence of ME in modem times"(1)
Can such a challenge be ignored? Does it stand up to my own experience of
clinical and laboratory medicine in the NHS (including the years of epidemic
and pandemic ME between 1965 and
1990)? Of course not! - but first we have to define the thyroid problems under
discussion.
2. DEFINITIONS:
The above quotation refers only to thyroid deficiency and hypothyroidism
which, by definition, is the clinical state resulting from underproduction and
lack of secretion of the thyroid gland hormones.
3. PHYSIOLOGY(2)
Thyroid hormones are unique in
that they incorporate an inorganic element (iodine) into the organic structure
of both hormones produced in the thyroid gland. These are Tetra-iodo Thyronine
(known as Thyroxine or T4 and Tri-iodo-Thyronine (known as T3). The main
hormone produced is T4, which acts as a "Pro-Hormone". T3 is produced
in small amounts by the thyroid gland, but is mainly produced in other tissues
from chemical conversion of T4. The T4, therefore, acts as a thyroid hormone
reservoir from which the body can make T3 as needed. It is this T3 which is
responsible for most of the thyroid hormone actually in the body.
4. THERAPY OF HYPO THYROIDISM(2,3,5)
Therapeutic replacement of thyroid hormones in deficient individuals by T4 (thyroxine) and not by the more active metabolite (T3) is usually chosen to imitate the physiological situation. The aim is to restore normal levels of thyroxine and (by negative feedback to the pituitary gland) to reduce associated high levels of thyroid stimulating hormone to normal range at the same time.It can be recognised from the diagram(Fig.1 Ref.2) that the entire process of producing thyroid hormones depends upon a series of interrelated balances and checks. These include inhibiting or releasing hypothalamic and pituitary hormones, while the thyroid gland itself exerts negative and positive influences over both master (controlling) glands.
The system is also linked (via the pituitary gland
and the HPA axis) to the adrenal gland the body’s main defence against stress.
Disruption of this axis by overproduction or prescription of thyroid hormones
can cause life-threatening adrenal gland failure.(3)
One has to imagine the hypothalamus, with its input
of information derived directly from the central nervous system, as the captain
on the bridge of a ship relaying positive and negative messages and receiving
positive and negative replies from a crew with many different functions. Lack
of co-operation, discipline and control can easily sink even the most solidly
built vessel.
Unless we have considerable clinical experience and
reliable scientific knowledge from laboratory support, we tinker with this
finely adjusted system at the peril of our patients.
5. WHAT IS THE
FUNCTION OF THE THYROID GLAND? (2)
Thyroid hormones increase the basal metabolic rate
of the body and improve oxygen uptake and heat production. Additionally they
increase the heart rate, cardiac output, alter body temperature and ventilation
rates in support of these activities. Other effects on the brain and skeleton
are essential to normal growth and development. A patient who is seriously
deficient in thyroid hormones will usually be female, elderly, cold, living
in poor conditions and mentally sluggish or comatose - easily distinguishable
even from those suffering severe ME.
Very mild hypothyroidism can occur at any age and in
both genders with non-specific symptoms as a normal physiological
response to general illness. Both free T4 and T3 are marginally low: treatment
for 'hypothyroidism' cannot make them feel better because it cannot cure the
underlying illness.
6. WHAT ARE THE PRINCIPAL CAUSES OF THYROID UNDERACTIVITY? (3)
(1) Iodine deficiency - this is no longer
geographically widespread in developed countries since the introduction of food
supplements (e.g. iodised table salt in the UK).
(2) Autoimmune disease - this is now the commonest
cause in the UK. It occurs almost exclusively in females in middle life and
there is usually a family background of the same or various other kinds of
autoimmunity.
(3) Following surgery or similar tissue-destroying
treatment for hyner-thyroidism.
7. WHAT IS THE OUTLOOK FOR PATIENTS
WITH THYROID DEFICIENCY? (3)
The annual incidence is
very low in the UK (0.2% in women) and life expectancy is normal except for
acceleration of ischaemic heart disease, which should be subject to regular
screening.
8. IS THERE A PARTICULAR CONNECTION BETWEEN HYPOTHROIDISM & ME?
Yes, there are 3 special
circumstances in which vigilance is essential:
(1) SUB ACUTE THYROIDITIS (4,5)
This is a virus-induced infection of the thyroid gland caused by
enteroviruses, adenoviruses, or mumps virus. It is a common trigger of the onset of ME, but, because it causes pain in
the thyroid gland, jaw, ears, head and neck, it is often misdiagnosed as mumps.
It is a systemic illness, usually in females aged 20-40 years. Laboratory tests
indicate a raised ESR (a blood sedimentation rate associated with infection)
and increased production of thyroid hormones for 4-6 weeks.
Iodine uptake by the gland is
low because of virus damage to the specialist colloid and iodine containing
follicles where thyroid hormones are stored. The illness subsides gradually
during the next 6 months and may include temporary hypothyroidism
accompanied by circulating antibodies. Treatment is with anti-inflammatory
drugs. Anti thyroid drugs should not be given during the initial hyperthyroid
period. In our clinic at Basildon Hospital (where we screened 420 patients with
ME for thyroid problems (5)) 15/307 women (5%) suffered from this
illness (to which I can find only one reference in modern textbooks!)(4)
(2) SECONDARY THYROID DEFICIENCY (4) This is much less common
than primary hypothyroidism and sometimes results in shrinkage of the thyroid
gland. It is associated with primary defects in hypothalamic and pituitary
function (as in ME), It is already known that adrenal function is poor in ME (3)
and that overload of Thyroid hormones can precipitate adrenal failure.
(3) INAPPROPRIATE OR FACTITIOUS (UNINTENTIONAL) OVERDOSAGE OF
THYROID HORMONES (4)
This may occur when
patients, who have suffered a temporary
period of hypothyroidism, continue to take thyroid hormone preparations for
years without supervision or when thyroid preparations are bought from Health
Food shops in order to slim or to achieve athletic prowess. This can alter the
normal T4 : T3 ratio and lead to hyperthyroidism as well as suppressing the
production and effect of the pituitary stimulating hormone (TSH) on the
thyroid. Of only 2 male patients seen at Basildon hospital with thyroid
problems, one had been given thyroid supplements without confirmatory
laboratory tests, by a kindly London consultant (who thought he was just
depressed). Some years later, we had to stop all treatment and start again
after laboratory tests -
But it took some 6 years to
stabilise his initially mild hypothyroidism. Unfortunately it made no
difference to his ME, which required early retirement.
SUMMARY OF LABORATORY DIAGNOSIS OF THYROID
DEFICIENCY
PRIMARY
HYPOTHYROIDISM:- This involves measurement of the two hormones involved in the
"checks and balances" system (fig.1) T4- thyroxine itself - and TSH -
the pituitary hormone which drives the thyroid gland. Normally the "free
T4" (circulating in the blood) is measured because this is the most
accurate indicator of the thyroid deficiency. One can expect a high TSH
and a low (or lowish-normal) free T4.
SECONDARY
HYPOTHYROIDISM:- If the T4 only is low,
other tests must be done to make sure the condition is not secondary to other
glandular dysfunction (e.g.: hypothalamus or adrenal as in ME). All ME patients whether diagnosed or suspected
must have TSH and free T4 tests as well as a 9a.m. serum cortisol level
performed to avoid adrenal failure!
DO THYROID
SUPPLEMENTS SUPPLIED WITHOUT CONFIRMATORY LABORATORY MONITORING HELP ME
PATIENTS?
(1) Well, not in my clinical
and laboratory experience of ME as it makes it more difficult to diagnose
any underlying hormone imbalance and to correct it, if necessary, in the right
direction.(5)
(2) Where hormone imbalance is
so slight as to be virtually incapable of measurement by routine laboratory
methods and where (it is claimed by those who advocate hormone supplements
without prior laboratory testing) that the patient is clinically hypothyroid,
I have to ask why all the additional diagnostic tests are not applied?
These include haematology
(for anaemia) pituitary and hypothalamic hormone levels (to indicate secondary
hypothyroidism and the danger of adrenal failure), Immunology (for antibodies)
ECG (for associated cardiac defects) and Histology (for lymphoid enlargement or
nodular defects of the thyroid gland (3) to exclude goitre or
cancer.
(3) Finally, the results of the
only randomised double blind placebo controlled trial of thyroxine treatment in
patients with symptoms of hypothyroidism (but with thyroid function tests
within the reference range) indicate that thyroxine did not improve cognitive
function and psychobiological wellbeing in healthy controls and was no more
effective than placebo in patients said to be clinically hypothyroid but with laboratory
tests in the normal range.
CONCLUSION - CAN A LITTLE OF WHAT YOU FANCY DO YOU
GOOD?
In the present era of scientific and evidence based medicine one is
obliged to count both the monetary and psychological cost of what is prescribed
and/or advised for patients.
1. It
would appear that the above placebo controlled trial indicates that medication
without laboratory monitoring is likely to be expensive in terms of ineffective
remedies and possibly of delayed or inappropriate treatment.
2. The
costs of psychological disappointment and despair are incalculable.
3. A
glance through the Southend Hospital Clinical Chemistry Department library is
informative and sometimes terrifying in respect of the safety of alternative
remedies advertised equally for slimming, body building and thyroid deficiency.
Hazards noted include interaction with other drugs or laboratory tests and
contents include "multi glandular complexes" from raw Bovine
meat including liver, lung, spleen, pancreas, kidney and brain. "Armour Thyroid"
which is highly recommended by the Practitioners mentioned in reference to
these problems(1) consists of Bovine thyroid gland which, of
course, cannot be sterilised.
CONCLUSION
I fully
understand the despair of patients and the impelling desire of kindly doctors
to prescribe almost anything to relieve their anxiety and pain; but in testing
our pet theories against scientific facts and common sense, I am always
reminded of an unfortunate Mr Day who tested his firm conviction of right of
way against a London bus - he was right, dead right, as he strode along, but
he's just as dead as if he were wrong.
As we enter
the 21st century, there is a greater need than ever for doctors and
patients to share knowledge and experience towards a common goal of obtaining
fair, speedy and effective means of preventing the current neglect and
deterioration of patients with ME.
E.G Dowsett MB,ChB.Dip.Bact.
Honorary Consultant
Microbiologist
Basildon and Thurrock
General Hospitals NHS Trust
Member of the Chief Medical Officer's Working Party on ME 1999-2002
References
1. JONES D. Thyroid Problems, The link with 21’st
Century Diseases, what Doctors don't tell you, 2001:12(9): 1-3.
2. Principles and Practices of physiology
2ndEdit, 1996 BERNE PM, LEVY MN (Eds;)MOSBY -year Book Inc 11830 Westline
Industrial Drive, St Louis, Missouri 6.3146, USA,
3. MEDICINE, AXFOPD J (Ed)
Blackwell Science Ltd,, P 0 Box 269, Abingdon, Oxon 0X14 4XN.
4. Davidson's Principles and Practices of
Medicine l7th edit 1995,(EDWARDS CRW, BOUCHIER IAD, HASLETT C. Eds,) Churchill
Livingstone, Robert Stevenson House, 1-3 Baxter's Place, Leith walk, Edinburgh,
EHI 3AE.
5, DOWSETT EG, RAMSAY AM, MCCARTNEY RA, BELL E.
Myalgic Encephalomyelitis a personal enteroviral infection? Post Graduate Medical
Journal 1990; 66: 526-530.
6. POLLOCK MA et al. Thyroxine Treatment in
Patients with Symptoms of Hypothyroidism but thyroid function tests within the
reference range. British Medical Journal 2001; 323: 891-895,
7, Natural Medicines Comprehensive Data Base 2002; 209 : 472-2244,
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