Don't the BTA, BTF, ACB EVER listen?

[Guest guest]

I am posting this long letter from our Dr Gordon Skinner to

Dr Beastall (Association of Clinical Biochemists) who, in partnership with the

British Thyroid Association and the British Thyroid Foundation created the UK

Thyroid Function Test Guidelines. This letter was written in 2005, and

obviously, no attention was ever given to his comments. You may wish to comment

on this yourselves.

, do you believe the following would be of any benefit to

the Investigators of our Official Complaint regarding the reasoning behind certain

organisations boycotting any T3 containing products - not only do these

organisations not take into account the views of other endocrinologists, neither

do they take account of the views of patients? Not one of Dr Skinner's comments

were taken into account by the creators of these guidelines.

Luv - Sheila

________________________________

22nd

December 2005

Dr.

D.G.H. Beastall

Secretary

Guidelines Development Group

British Thyroid Foundation

Department of Clinical Biochemistry

Royal Infirmary

Glasgow

G4 0SF

Dear Dr.

Beastall

I thank

you for allowing comment on your consultation document.

General Comments

One of

the difficulties with Guidelines in modern day medicine is that there cannot be

divorced from political and regulatory influences. I hope you will thus forgive

a few comments on your hard work.

There is

no doubt that in the present environment Guidelines tend to transmute into

rules and caveats or reasonable argument against any aspect of such Guidelines

becomes lost in time. In the unusual environment of modern day clinical

practice, there is little doubt that to waver from Guidelines – once they

have become enshrined in publication – becomes dangerous territory for a

practitioner; Indeed colleagues involved in regulation of medical practice tend

to reply more and more on Guidelines compounded by the difficulty that expert

witnesses will often be lauded for quoting Guidelines rather than invoking

their own (sometime) extensive experience in a subject which will not be

considered “evidence based medicine” albeit culled over 40 years of

hard won toil. It is thus crucial that the medical profession acknowledge and

state in the public domain that Guidelines are there to assist practitioners

but are not sticks to beast them if they fall out of line.

Guidelines

usually proclaim the value of “evidence based medicine” wherein

clinical evidence – for example if the patient says he/she is not feeling

well – is somehow less weighty than evidence based on laboratory

findings, albeit that this philosophy is selectively applied and there is

little laboratory evidence for the extensive display of Prozac, Seroxat, etc.

Endocrinology and particularly hypothyroidism have elevated laboratory-based

medicine to a level which frequently gainsays unequivocal clinical evidence and

the clinical features are then bizarrely ascribed to depression,

peri-menopausal state (which used to be considered physiological) or over

eating or a somatiform illness albeit the patient has classical features of

hypothyroidism. THS situation is compounded by the political legal regulatory

pressures, wherein a practitioner, who disclaims the diagnosis of

hypothyroidism if the thyroid chemistry is “normal” – usually

within a 95% reference range – will receive no disapprobrium from peers

or regulatory bodies, while practitioners, who diagnoses and treat patients

with due cognisance of clinical evidence in the face of “normal”

thyroid chemistry are in treacherous territory and is usually considered the

province of marginal practioners (often “private”) who have not

quite got their heads round the concept of evidence based medicine, albeit the

patient returns to optimal health following thyroid replacement.

In

summary, there is significant pressure on practitioners to use laboratory

chemistry as a keep-safe to not make a diagnosis in the face of over whelming

evidence of the condition.

It is

pivotal that there is no confusion on this issue. Few practitioners will not

agree that if a patient has high TSH level or a low FT4 level, that that

patient is likely to be unwell and suffering from the clinical features of

hypothyroidism. The mischief lies in assumption of the reciprocal and I am

unaware of any evidence which teaches that if you have clinical features of

hypothyroidism with reasonably normal thyroid chemistry, that the patient does

not suffer from hypothyroidism and will not benefit from thyroid replacement.

Two studies have tried to examine this issue.

Doctor

McLaren’s group examined this matter in a left-handed way, although this

was not the primary purpose of this study (1). The study identified patients

who were deemed to have hypothyroid features but normal thyroid chemistry,

which in itself, somewhat supports the notion. However, treatment in these

patients did not reveal significant improvement. It is the easiest thing in

this world to criticise a colleague or a colleagues work, but there were

certain aspects of this trial which might explain the poor response to treatment

and these points are engrossed in an enclosed note (3) where I have tried to

argue these issues, and encourage investigation of this whole question of the

diagnosis of hypothyroidism.

In our

town centre, we conducted a temporal analysis of the results of treatment in

patients who were diagnosed largely with depression or chronic fatigue like

syndromes and who had normal thyroid chemistry, but clinical features of

hypothyroidism and it did seem, that these patients improved significantly (2).

This was not a placebo controlled trial, but the importance of the two studies

rests in the original observation and selection of patients where it did seem

that there were patients who had clinical features of hypothyroidism with

normal thyroid chemistry and certainly, in one of these studies, there was

improvement in the clinical status of most of the patients following thyroid

replacement. It is crucial to institute formal clinical trial, but to date; we

have been unable to obtain funding for this purpose.

The only

other evidence (which one hesitate to include in these strange times) is

clinical observation over many years, and in my own practice, I have seen many

patients in this situation who returned to optimal health following thyroid

replacement. While appreciating that statements of this nature will not only be

discounted by (particular) younger colleagues and considered to be yet another

example of the kind of thing that colleagues who do not understand evidence

based medicine are inclined to say “I feel I am a (relatively) sane

citizen (and indeed lectured in statistics in the University of Birmingham in

an earlier life) and am not embarrassed to make such a statement and request

that it be entered into the portfolio of information on this matter.

I

earnestly urge that this document makes an unequivocal statement that there is

no evidence to suggest that normal thyroid chemistry excludes a diagnosis of

hypothyroidism; this simple statement written in bold (I trust) may save

literally thousands of patients during the next two decades from the

unqualified misery of untreated hypothyroidism.

II. Thyroid Hormone Levels

Reliance

on thyroid chemistry is a backward, rather than a forward step and I have

previously presented a number of arguments in support of this view (1,2,3 and

4). Two additional general points may be germane.

Critically,

the tests measure the presence of thyroid hormones by immunological methods and

it is well recognised that antigenicity and indeed, immunogenicity will survive

deactivation – for example, formalin or phenol treated vaccines –

and the immunological epitope can, and often does survive, in a chemical

moiety, but there is no hormonal or enzymatic activity left in the molecule;

this is well recognised in cellular biology. There is indeed, clinical evidence

of this, in that I have come across a few patients whereby mischance, they had

staggeringly high levels of thyroid hormones – for example FT4 reading

above 100.0 – yet the patient seemed not in the slightest thyrotoxic and

indeed, one of the patients was still clearly, hypothyroid; it is also true

that many patients feel best when their FT4 readings are over 30.0 and have no

clinical evidence of thyrotoxicity and until there are measures of the

biological activity of these hormones, it is surely errant to equate biological

activity with immunological presence; a graveyard has a high density of people

with little activity.

Reference

intervals – which depend on the size and nature of the population

selection – often misleads. The distributions are skewed and a 95%

reference interval indicates the 5% of the global population lie outwit this

range which is cheerily ignored when a patient has their level of medication

slashed, if their FT4 (for example) is a decimal point above the upper limit of

a 95% reference interval; moreover, if a patient is within a 95#% reference

interval, they are deemed, for some obscure reason to be in good health,

thyroid wise. But if – as obtains within 5% of the globe some 500,000,000

people – are just above the upper limit of the reference interval, few

practitioners would seek to proclaim that they are hyperthyroid! It should be

emphasised that the statistical concept of a reference interval is a different

issue from a health cut-off point, or some kind of regulatory meter in a

machine where there is a safety zone and cut-off zone, and where to stray out

of the zone is dangerous or instantly indicative of good or bad health. I hope

you will not feel I am over labouring this point, but there is little doubt

that this mode of thinking is operative for many practitioners when assessing

the diagnosis of hypothyroidism and the notion that the patient’s

personal computer – which is their brain – can incorporate,

integrate, and distil a multitude of information is lost ion a legally driven

misinterpretation of statistical scatter.

III. Miscellaneous comments on text

3.1.1

Para.1. Patients who have no symptoms are surely not suffering hypothyroidism;

I wonder if this would not be defined as subclinical hypothyroidism if there

were coincident abnormal thyroid chemistry. Para. 2. The first sentence is

self-obvious, as everyone will agree that, for example, fatigue has a large

number of diagnostic aetiologies. I really do not agree with the second

sentence; I think that most colleagues would agree that Goitre with an enlarged

tongue would point in the direction of hypothyroidism and over the years, I

have found that patients with side vision hallucinations, or hallucination of

objects on the floor relating to mucupolysaccharide opacities in the eyes tend

to be associated with hypothyroidism. Most patients can be diagnosed by

clinical features and this was once the only system of diagnosing

hypothyroidism; I am unaware that results were worse prior to institution of

thyroid chemistry, but I have no evidence that this is the case. The last

sentence of para. 2 again, suffer from the “assumption of

reciprocal”; are you really contending that a patient with a TSH of 9.9

should be considered to not have hypothyroidism? I think an unequivocal statement

in this matter would be important.

Para.3.

Is there a mix-up between sub-clinical, which means no symptoms and mild

hypothyroidism, which would mean symptoms of hypothyroidism in small measure? I

have seen many patients who have normal FT readings and are in fact very ill

and I do think that this statement will confuse colleagues for years to come.

Para. 4.

I do strongly disagree with this paragraph, in that it is at odds with clinical

experience of many practitioners over many years. The first two bullet points I

think are not true, and the second bullet point again suffers from the danger

of assumption of the truth of the reciprocal which would leave many patients

untreated.

3.1.2. I

feel I am being tedious, but titrating dosage by laboratory tests may have

become the “mainstay” with certain practitioners, but this should

not be construed an optimal approach. It was shown, for example, some decades

ago, that smaller doses of thyroid replacement would reduce TSH level, but many

patients do not feel well until the TSH approaches zero. You are surely not

advancing that a TSH level just below the upper limit of the reference interval

indicates satisfactory replacement as in quoted references no. 18 and No, 19;

The average for health patients lies around No. 1, a TSH of 4 times the average

would be (usually) within a 95% reference interval, and surely not the

objective of treatment.

I do

earnestly urge that this concept is removed from the Guidelines and the

mainstay of treatment should be when the patient has returned to feeling well

with no residual hypothyroid features’ this principle will ensure that

the present catastrophic situation where patients continue to be unwell, on

account of TSH level, will not continue for future decades.

Para. 2.

(Page 27) I did wonder if this was unnecessarily complicated, in that

preventing over-replacement is an “axiomatic schedule”. However, if

patients are replaced in small increments then this will not occur, and if

clinical features of over treatment develop, then the dose can simply be

reduced again. It would simplify matters if all patients – short of

hypothyroid emergencies, are started at 25 mcgs thyroxine for 1 week and then

proceeding in 25 mcgs integers at sensible intervals. Cardiac complications

have been seriously over emphasised and I think it would be useful, in the

Guidelines, to mention that the main threat to cardiac status is continuing

hypothyroidism with low physical activity, hypercholesterolaemia and deposition

of atheroma; the latter has been significantly under noted in recent years, but

featured highly in the earlier literature on the subject.

Para.3.

Again, the assumed reciprocal; one asked the Development Group how secure they

feel is the information that patients do not feel better if the TSH is below

2.0. In my own experience, and indeed in our published work, we found a rather

poor relationship between TSH levels and clinical well-being.

Para.5.

The most crucial aspect is how the patient feels, and not levels of these

hormones. I would seriously contend that there are thousands of patients who

are maintained in a state of sub health, because it is deemed that either TSH

or FT4 are at satisfactory level, and indeed in some measure, the next

paragraph (Para. 6.) does address the issue of the perfidy of using these

levels as exclusive criteria.

Para. 6.

I cannot agree with bullet points 1 and 2, particularly 2; surely a primary

target of replacement is to restore clinical well-being.

I agree

with the FT4 reading in patients taking triiodothyronine. I have come across a

few patients who were taking T3 only and had a FT4 of zero, which rather

confused certain laboratories.

Again,

we are back to the reciprocal point, and to my knowledge, there is no evidence

advocating that thyroxine alone is preferable to the combined therapy and, dare

I say it, I have often noted patients to be considerably better using the

combined therapy, but it is possible that the patient is merely having a higher

level of replacement. On balance, I think that certain patients do benefit from

combined therapy.

Again, I

do not agree with the objective of therapy which should be return of well being

and it happens in many patients who are still unwell and in fact, do not become

well until the TSH is well below the lower end of the reference interval.

3.1.5. I

do have some reservations about the “excellent automated format”

which may be logistically efficient as a call-up system, but I have

encountered, in a number of patients who are significantly disenchanted, in

that they go for a blood test, and this is it, and nobody speaks to them or, in

essence, attempts to discover how they do feel.

Summary Points on Guidelines

The

following are major points with which I am in disagreement vis-a-vis the

Guidelines. I will preface these points by indicating that I appreciate, only

too well, how much hard work and consultation has gone into the preparation of

these Guidelines, although I do wonder if, perhaps, rather more consultation

with patients or even thyroid “self-help groups” who might have

perhaps, influenced major conclusions. I do formally thank Dr. Beastall and his

colleagues for carrying out what is often a somewhat thankless task; it is only

too easy these days, to put one’s head below, rather than above the

parapet.

Summary Comments

The

predication that criteria for diagnosis and dose level of thyroid replacement

should be based on thyroid chemistry is doomed to failure; I have observed this

over many years of practice.

Thyroid

hormone levels, in particular thyroid and thyroid stimulating hormone, within

95% reference interval, does not equate with health or euthyroidism; there is

no evidence to support this contention but a measure of evidence from 2 studies

(1,2) and from clinical experience over many years, that this is not the case.

I believe that this must be clearly stated in the Guidelines to avoid

condemnation of many patients to continuing hypothyroidism based on this

misassumption.

Laboratory

tests for thyroid hormone levels do not measure biological activity and the

adoption of reference ranges as “action parameters” is a

significant problem in the diagnosis and treatment of hypothyroidism. This

results in a serious shortfall in care with inadequate replacement based on the

notion that TSHG levels should be returned to somewhere within the reference

interval. TSH values have a left-sided skewed distribution and a value of, say,

2.5 is well within the average TSH level, which runs around 1.0 in most

laboratories; thus, the contention that a patient is satisfactorily treated if

they have a TSH which has declined to a level of (approximately twice the

healthy average) is clearly in error. This mischief is compounded by anxiety

over suppressed TSH. I believe that any perceived long-term detriment from

suppressed TSH levels in a healthy patient is infinitesimal compared to the

unequivocal detriment of inadequate replacement and continuing ill health.

Advise

on FT4 higher levels seem overly cautious. Whilst some patients are returned to

optimal health, with an FT4 reading toward the upper end of the 95% reference

interval; I would have thought that a number of Endocrinologists would agree

that in a patient with no clinical evidence of thyrotoxicity, there is little

to be feared from a patient with FT4 readings, even approaching 35.0; It is

difficult to believe that clinical euthyroidism is accompanied by unsuspected

detriment from raised FT4 reading. Account must be taken of previous caveats

concerning thyroid hormone estimation and pharmacological considerations where

intracellular uptake rate or deactivation or neutralisation of thyroid hormones

highlight the ill advisability of equating thyrotoxicity with a high level of a

hormone which may not be de-iodinated effectively, or maybe inactivated, or may

not be uptake by the cells in vivo; it has always been a mystery to me that my

colleagues purport thyrotoxicity solely based on a hormone level in patients

who are manifestly not thyrotoxic.

In

summary, the major point of disagreement with these Guidelines rests on my

earnest belief that exclusion of hypothyroidism through the criterion of normal

thyroid chemistry will frequently miss the diagnosis and titration of dose

levels through thyroid chemistry, will result in patients being chronically

under treated with serious health risk. There is an overwhelming need for a

properly controlled clinical trial to assess the results of thyroid replacement

in patients who are clinically hypothyroid with normal thyroid chemistry and a

prospective or even retrospective investigation of any detriment to health, in

a patient who is clinically euthyroid but whose thyroid chemistry falls outwit

95% reference intervals. Both of these studies are ethical and should be

undertaken with expedition.

Yours

sincerely,

Gordon

R.B.Skinner MD.DSc. FRCPath, FRCOG

References:

Thyroxione treatment in Patients with Symptoms of Hypothyroidism but Thyroid

Function Tests within the reference range: Randomised Placebo Controlled

Crossover Trials: Pollack MA, Sturrock A, Marshall K, son K M,

C.J.G, McMahon A D, McLaren E H, BMJ 2001 323; 891-895 (20th October)

Clinical

Response Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid

Patients: GRB Skinner MD(hons) DSc, FRCPath, FRCOG. D Holmes, A. Ahmed PHD. GA

Davies, BSc. Benitez MSc. Journal of Nutritional and Environmental Medicine

(2000) 10, 115- 124

Letter

to Sir McCormack FSA; MP. 02.12.2005

Diagnosis

and Management of Hypothyroidism. GRB Skinner. Louise Lorne Publications.

Birmingham UK 2003

[Guest guest]

Awesome letter

answer to the question headed in the post seems to be

NO they don't listen.

Hope can advise.

lotsa luv

Dawnx