Thyroid function tests—time for a reassessment
BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7245.1332 (Published 13 May 2000) Cite this as: BMJ 2000;320:1332All rapid responses
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Sirs
I have read with great interest the article by Denis StJ
O’Reilly "Thyroid Function Tests – time for a
reassessment" and the correspondence it provoked.
I am a hypothyroid patient living in France and my
experience in achieving satisfactory diagnosis and
treatment of my condition has been very similar to that
experienced by the many thousands of patients in the
United Kingdom and the United States who have
described their medical experiences in great detail and
over many years on the internet forum
http://thyroid.about.com. This forum must constitute the
largest single source of anecdotal evidence of the
inadequacy of current diagnosis and treatment of
thyroid patients the world over.
The following hypotheses emerge from a detailed
analysis of research published in medical journals
(principally in the United Kingdom, France and the
United States), from the interviews and publications of
those few medical practitioners and researchers who
diagnose and treat outside the dictates and current
practices of the medical establishment, and from the
multiple experiences of patients.
Hypothesis One
The Thyroid Stimulating Hormone (TSH) test, currently
the most widely used blood test worldwide to diagnose
thyroid dysfunction, is an unreliable test of thyroid
function that has no proven scientific biochemical
basis. Anecdotal evidence indicates that the
biochemical diagnosis of hypothyroidism with the TSH
test is very poorly correlated with a clinical diagnosis of
hypothyroid symptoms.
Free T3 and free T4 tests are reliable and anecdotal
evidence demonstrates that these are the only
biochemical tests of hypothyroidism to show a
satisfactory correlation with clinical diagnosis.
A diagnosis of hypothyroidism should always be made
on the joint basis of biochemical tests of proven
scientific validity and of the assessment of clinical
symptoms.
Hypothesis Two
The therapy generally upheld by the worldwide medical
establishment as the only appropriate treatment for
hypothyroidism, synthetic T4-only replacement therapy,
does not relieve the symptoms of hypothyroidism in
many hypothyroid patients.
Synthetic T3-only replacement therapy is difficult to
administer and can be dangerous.
Synthetic T3 plus synthetic T4 replacement therapy, in a
ratio similar to that found naturally in the human body,
does relieve the symptoms of hypothyroidism in most
patients and, what is more, is safe, available at low
cost and easy to administer.
To my knowledge, in recent times there have been two
small animal trials (Escobar-Morreale et al, Madrid,
1995 and 1996) and a single small-scale human
clinical trial (R Bunevecius et al, 1999) to investigate
Hypothesis Two and no clinical trials to investigate
Hypothesis One.
In the absence of a large authoritative clinical study to
validate these hypotheses, current opinion and practice
of the worldwide medical establishment in the
diagnosis and treatment of hypothyroidism is unlikely to
evolve. Until such a study is carried out, many millions
of patients will continue needlessly to be
misdiagnosed and mistreated, with the resulting
individual cost to quality of life and collective cost of
ill-health.
Yours faithfully
Anna Perry
Competing interests: No competing interests
It amazes me that in this technological revolution we are now in, and
the supposed awareness and sensitivity of our time, why so many medical
practioners are unable, unwilling or both, to focus on an illiness that
would be so lucritive, not only would all of us sufferers benefit from
proper treatment but so would the medical community and drug manufactures
at large.
I'm curious if all the hormones excreted by the thyroid have been
identified? Does it make sense to treat a patient,who's thyroid is shut
down with a straight dose of T4 when perhaps the conversion mechinism to
T3 is "broken" or there are several other hormones unaccounted for?
Wouldn't that alone lead to an imbalance?. In my case, appr. 3 years ago,
I was diagnosed with a slow thyroid with a TSH in the severely abnormal
range. After repeated complaints of lethargy, appettite
stimulation,carbohydrate cravings, and weight gain my physician would not
up my dose of Hormone, I have since been to two other physicians who are
working with me just to get me in the range of normal, both in TSH and
energy. I am sick and tired of being tired.
In the article the hypothalamic-pituitary-thyroid axis is mentioned,
which leads one to believe there is a play on the neuro-transmitters in
this disease, the physiological symptoms one exhibits such as food
cravings, weight gain, etc., could possiblybe symptoms of seretonin
levels. Perhaps we're looking in the wrong area, perhaps the problem
begins in the brain and has a trickle down effect to the thyroid, Is
anyone looking into this possibility?
Competing interests: No competing interests
The dubious nature of thyroid function test is not an accident it is
a cultural necessisty.
Down the ages the fundamental problem of the healer has been to avoid
taking the blame for the inadequacy or detriment of the attempted remedy.
The method adopted has been to scapegoat the patient. This has to be done
cryptically. The method used is to blame the patient for the disease and
to interpret the disease in a way that degrades the patient - one must
always degrade the scapegoate, one does not say 'the gypsies are to blame
and the gypsies are saints and heroes.' In the case of a child a
convenient adult is blamed or degraded, hence 'shaken baby syndrome.'
In the past disease was a punishment from God for sin, in the present
the preferred method, amoung many methods, is to call the disease
psychological. It is essential that any diagnostic test must permit the
blaming and degrading of as many patients as possible.
Competing interests: No competing interests
I would like to give my experience of the consequences of undiagnosed/treated subclinical hypothyroidism. I am presenting
with many clinical symptoms of hypthyroidism, blood tests for antibodies are positive, and I am told by my GP that I am
borderline hypothyroid. I have a lot of respect for my GP but she subscribes to the conventional definition of normal thyroid
function based on blood tests.
At the same time I am experiencing menstrual irregularities and have read that these can be another symptom of
hypothyroidism, yet when I brought my borderline status to the gynaecologist's attention three times he ignored it. Instead,
despite having no risk factors for cervical cancer, having had two pelvic scans and a smear which were all clear, he has
suggested I come in for an overnight stay to have a hysteroscopy and a D and C "as it was the only thing they hadn't done".
As a lay member of the public a simple risk/benefit analysis of a trial course of thyroxine versus a general anaesthetic and a
possibly totally unecessary D&C would seem to be clear cut in favour of trying treatment for the thyroid (especially as he
suggested my overweight would present an additional risk with the D&C). In other words the absence of a diagnosis and/or
treatment for subclinical hypothyroidism has led me to be offered a far riskier procedure.
I have decided to trust my own layman's knowledge and am not going to have the D&C at this stage but await the results of
my latest thyroid function test. I present this example as I believe this sort of consequence also needs to be factored into the
equation when assessing the risk/benefit of treating subclinical hypothyroidism.
Competing interests: No competing interests
I am hypothyroid and have been for some time. Both my parents and my
sister have thyroid disease. I had a 150% alteration in my TSH which was
6.4 and my GP was still reluctant to treat me as this was in her view
'just outside the normal reference range of 5.5.' I exhibited very many of
the clinical symptoms but was considered a 'difficult patient' when I
insisted on a referral to an endocrinologist who was also reluctant to
treat me. I very much welcome the debate stimulated by this article and
would urge all GPs and endocrinologists to listen more closely to their
hypothyroid patients and to not dismiss their continuing health problems
simply on the basis of numbers. Doctors must help patients with thyroid
disease to be as well as they can be and patients should not be expected
to settle for anything less! However, the debate needs to be widnened as
some of your correspondents have already indicated. I take Armour thyroid
as my symptoms were not alleviated by thyroxine and have to pay for this
privately as I have been advised it is not available on the NHS. Well - it
should be as thyroid patients are all individuals and the same treatment
does not work for everyone.
Competing interests: No competing interests
Although I found this article to be extremely true based on the many,
many people I have come across with this disease through websites, support
groups and my own personal experience, it is still a disgrace in the way
that which thyroid patients are treated and mishandled by their
physicians.
I remember first being diagnosed and told that the symptoms I was
describing were related to my Hypothyroidism. I also remember that once
my TSH was in the range that my endocrinologist felt was good, I was then
told that the same exact symptoms that I had been told were a result of my
Hypothyroidism initially, were then dismissed and I was then told that a
good Psychiatrist was in order based on the fact that my numbers were good
and I no longer had a thyroid problem.
Most of the thyroid patients I have come across, as well as myself,
have been totally frustrated because they know that they are being
undermedicated but can't do a thing about it. Their hands are tied as
they depend on their physicians for the medication and being as most
physicians believe that the TSH is the answer to all it is very difficult,
if not almost impossible, for most to be treated adequately.
Many, many thyroid patients have been totally disabled. They can no
longer work because of their condition and most are being told when their
numbers look good that it must be something other than their thyroids that
are causing the problem. They are sent to every specialist under the sun
and almost always given anti-depressants and declared to have mental
problems or even be hypochondriacs.
There are very few doctors out there who handle hypothyroidism
clinically. Doctors seriously need to be retrained in how to clinically
diagnose and treat this disease. Even those who realize that they are
being undertreated cannot get their doctors to increase their medications
and continue to suffer. It seems to me that patients are totally being
dismissed because of a test. I have heard many go to their doctors
complaining of clear hypothyroid symptoms and even being told by the
doctor that they sounded hypo only to be turned away once the blood showed
otherwise.
I think that answer lies in going back to clinically recognizing and
treating Hypothyroidism. However, the majority of doctors go by the tests
and it is only the minority who clinically treat. Those of us who have
been lucky enough to get clinically treated are still in a bad place
because of the fact that once these doctors who clinically treat are gone
we will be thrown back to the wolves and be treated by TSH again leading
to most of us to have our medications reduced.
I think about it everyday what I will do when my present doctor
retires and can no longer treat me. The medical establishments beliefs
about this condition need a serious overhaul but what can we do as
patients to change this? I worry about the health of my children being as
since there are other members of my family with this disease that their
odds of getting it too are pretty good. I certainly would like to see
thyroid disease handled differently because I would never want to see my
children suffer they way I and countless others have had to.
The TSH, in my opinion, definitely has to be questioned. As Dr.
Broda Barnes pointed out so beautifully in his book, there were many other
tests before TSH that were touted as being the best and most improved and
then later proved to be not as accurate as thought. The TSH test has
been improved through the years which leads to the assumption that they
also didn't have it right the first time. How can we put all our trust in
these tests despite the patients clinical picture?
I for one, as well as many other patients, wish we could go back to
the days before TSH. I happen to have had older members of my family with
thyroid disease who had the disease before TSH and none of them had
problems. They were treated based on their symptoms and recovered. The
way things stand now, not only are we being undertreated, our chances for
a full recovery since we are going undertreated for so many years is
slipping away.
I don't think it is fair that we are being denied our health and
happiness based on some silly test. If the test was so accurate, there
certainly wouldn't be so many with this condition who are still ill
despite treatment and good numbers.
I have read Dr. Derry's materials and according to what I have seen
in my own family members before TSH as compared to the people who
currently have hypothryoidism and are being treated by TSH, I think he is
absolutely correct and that there should be more doctors with his thinking
and understanding of this disease.
Not only is a severe reassessment of TSH needed there is also a
severe need of retraining of doctors in how to clinically diagnose and
treat this condition.
Competing interests: No competing interests
Unfortunately this disturbing article confirms what many thyroid
patients have suspected- that their symptoms, because they tend to be
diffuse and vague, are being disregarded, and their own awareness of their
illness undervalued. The classic comment made by one endocrinologist to a
patient with toxic multinodular goitre was, "I have no interest in
how you feel"!
Medicine is an art as well as a science inasmuch as itrequires not simply
an ability to read results (which seem in any case to be based on an
alarmingly small sample), but to interpret a patient's symptoms. If the
education of doctors does not stress the importance of listening to the
patient and observing the different symptoms manifesting in different
patients, it is grossly deficient.
As a patient I am fortunate in having a sympathetic GP who is aware that
the quality of my life matters as much as my test results. The impression
I gain all too often from other patients is that some doctors have simply
no conception that the quality of the patient's life is as important as
their own. In the end it is arrogance that places a reliance on test
results- the doctor's knowledge- at the expense of clinical diagnosis of
symptoms- the patient's awareness.In treatment there is supposed to be a
partnership between patient and doctor, but this message does not seem to
have reached some endocrinologists.
Competing interests: No competing interests
The article plus its responses all highlight the despair so many
patients are facing when they are arbitrarily told "your blood tests are
in the normal range "
Worse still is when they are on Thyroxine and have been for years ,
their blood tests are WONDERFUL but the patient still feels lousy
No one listens, No one cares, no one does anything
they just pat them on the head and pretend its not happening
THYROXINE does not work for many many many patients BUT WE HAVE NO
ALTERNATIVE >>>>>>>>Why does someone not run a
proper trial of
Armour versus Thyroxine
Cytomel versus Thyroxine
Thyrolar versus Thyroxine
T3 versus Thyroxine
All the doctors in the USA who prescribe these with great succcess
CANT BE WRONG
Its grossly unfair to cast Thyroid patients on a scrapheap of pain
and disability dependant on incapacity benefit when they could be fit and
well if only someone listened
Competing interests: No competing interests
Dear Sir - With regard to the correspondence following my article of
the 13 May (1) I wish to make the following points.
I fully agree with Professor Kendall-Taylor when she states that TSH
assays are not infallible and must always be interpreted in the light of
clinical features, drug therapy, etc. I also agree with Drs Toft and
Beckett that there is nothing to be gained by those who advocate the
primacy of thyroid function tests or clinical examination and that the
correct diagnosis will be made on the basis of both clinical examination
and the results of the appropriate thyroid function tests. Though they
have not used the term in
their letters the sentiments they express in the final paragraphs I
interpret as acknowledging that thyroid function tests can give rise to
false positive results.
All agree that the clinical features of thyroid disorders are very
important. In my article I drew attention to the observation that the
clinical features of thyroid dysfunction are now very rarely aired in the
medical literature and as a consequence non-experts in the field are given
the impression that the clinical assessment of patients for thyroid
dysfunction is of little importance. Excellent descriptions of the
clinical features of thyroid dysfunction are given in publications such as
Dr Tofts book "Understanding thyroid disorders" (Family Doctor Series -
The British Medical Association )and "Thyroid disease - The Facts"
(Bayliss RIS and Tunbridge WMG - Oxford University Press) which are
written for patients.
I recommend these publications to medical students and trainees as
they contain clinical descriptions of thyroid disorders which are not
readily available from medical text books or journals. Sadly some have
the impression that, because these publications were written primarily for
patients , the data they contain , which is not available in the
conventional medical literature is of little importance. They receive
support for this view when they observe that groups who devised clinical
scoring schemes , such as The Newcastle Thyrotoxicosis Index (2) refered
to it in only the second edition of the texbook from that centre
(Fundamentals
of Clinical Endocrinology . Hall R , Anderson J & Smart G A ) and
dropped from subsequent editions when assays for Thyroxine , Tri-
iodothyronine and TSH became available.I think it is sad that the clinical
assessment of patients with thyroid dysfunction is the subject of public
ridicule ( see March of 1999 Calendar Prozac Delivers , Dista Products
Ltd.).
Price and Weetman stated that I suggested that the upper limit of the
reference range for TSH should be extended to 21.5mU/l. This is not so.
In my article I was pointing out that from our first experiences with the
measurement of TSH it was clear that there was a significant difference
between the Reference Range ( which is frequently refered to as the '
Normal Range ' ) and a Diagnostic Range. The Reference Range for serum
TSH that we established in our department using 497 subjects is 0.35 - 5.0
mU/l.
However not all users of Biochemistry laboratories appear to distinguish
between a statistically derived Reference Range, such as that used when
interpreting the serum TSH, and a Diagnostic Range which is used when
interpreting a plasma glucose or cholesterol concentration. In the case
of
cholesterol the statistically derived Reference Range bears no
relationship to the plasma cholesterol concentration used when
establishing risk factor status for coronary heart disease or the
therapeutic goals aimed at when treating patients. When one adopts
statistically derived Reference Ranges it is acknowledged that patients
will be misclassified.The reference range for serum TSH is too narrow to
be used as a Diagnostic Range.
Toft and Beckett state that finding an abnormal serum TSH in patients
taking thyroxine is an indication for adjustment of the dosage. In an
assessment of a third generation serum TSH assay by Franklyn and her
colleagues ( 3 ) they found that in 55 of the 153 patients taking
thyroxine
the serum TSH was below the functional sensitivity of the assay , that is
<0.03mU/l, which is an order of magnitude below the lower end of
statistically derived Reference Range. She and her colleagues stated in
the article that 'An important finding from the present study was the
observation that the serum TSH values were undetectable, even in the most
sensitive assays employed ,in subjects receiving long term T4 therapy ' (
3 ). This would suggest that to maintain the serum TSH concentration
within
the Reference Range derived statistically from a healthy population not on
thyroxine is an unachievable goal in some patients on thyroxine
replacement.
I fully endorse the view that serum thyroid hormone measurements are an
essential part in making a diagnosis of hypo- and hyper- thyroidism. I
would agree with the view that the statistically derived Reference Range
is
so narrow as to make the diagnosis of hypothyroidism in patients who have
a serum TSH concentration within the Reference Range , in the absence of
Hypothalamic-pituitary disease , virtually untenable. This is borne out
by
the findings of Pollock and her colleagues (4).
Denis O'Reilly
Consultant Clinical Biochemist
(1) O'Reilly D StJ. Thyroid Function Tests - time for a
reassessment.B.M.J. 2000:320;1332 - 4.
(2)Gurney C, Owen SG, Hall R , Roth M, Harper M, Smart GA , Newcastle
Thyrotoxicosis Index. Lancet. 1970 : ii : 1275 - 8.
(3)Franklyn JA, Black E , Betteridge J , Shepherd M C . Comparison of
second and third generation methods for measurement of serum Thyrotropin
in patients with overt hyperthyroidism , patients receiuving thyroxine
therapy
and those with nonthyroidal illness . J Clin Endocrinol Metab . 1994 ; 78
: 1368 - 71.
(4)Pollock MA ,Sturrock A, Marshall K, Davidson K ,Kelly CJ , McMahon
A , McLaren EH.Efficacy of thyroxine replacement in patients who feel
clinically hypothyroid but are biochemically euthyroid. J .
Endocrinol.2000 ; 164
(Supplement) : P329.
Dr.Denis St.J. O'Reilly,
Department of Clinical Biochemistry,
Macewen Building,
Royal Infirmary,
Castle Street,
Glasgow,
G4 OSF.
Competing interests: No competing interests
Point for clarification
Could someone clarify what exactly is the P in your formula Is this
just the probability?
{P/(1-P)}=bo +b1
Competing interests: No competing interests