Dear Sir - TPAUK



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Charity Registration Number 1138608

Thyroid Patient Advocacy challenges the Royal College of Physicians to end, once and for all, the long standing controversy between Endocrinology and the quarter of a million patients who continue to suffer the symptoms of hypothyroidism, even after the recommended treatment.

The RCP’s Curriculum Fails Doctors 

TPA believes that education on the subject of thyroid problems is flawed because of the failure of the RCP’s curriculum1 which goes against the requirements by the General Medical Council.2

There is no mention in the RCP curriculum of ANY training relating to peripheral metabolism and peripheral hormone reception physiology (Euthyroid hypometabolism)

There is no guidance in ‘The Map of Medicine’ 3 (accredited by the RCP) regarding recommended diagnostics and treatment of Euthyroid hypometabolism. The need for ‘other thyroid hormones’ is established by medical science,4-6 with incontrovertible potential for deficiencies in somatic functions,7-13 for example] and patient counterexamples.14

Euthyroid hypometabolism (EH) has been known to medical science for over 60 years, after medical practice had been warned of inadequate therapy with T4 monotherapy. This science has been ignored.

Yet, this practice not only persists, it has now been institutionalised by the RCP.15

Although it is alleged that the RCP policy statement refers only to primary hypothyroidism, it does make restrictions that go beyond primary hypothyroidism.

The majority of patients with the symptoms of hypothyroidism are diagnosed and treated reasonably however, many are not satisfied with their therapy.16

The universally accepted Differential Diagnostic Protocol17 requires the examination of ALL the physical issues, and recommends that ALL potential causes for the patient's symptoms should be listed and scientifically tested,18-21 before bogus, patient-blaming excuses are postulated, such as “functional somatoform disorder”, as cruelly propounded by Professor A P Weetman in his paper “Whose Thyroid Hormone is it Anyway?”22

The fact that mental issues cannot be tested objectively requires that they be regarded as a diagnosis of last resort. Sharpe, et al.,23 indicated that “symptoms are defined as ‘unexplained’ after disease has been excluded. Historically, which diseases have been considered necessary to exclude (and the means of detecting them) has depended on the state of medical science” as well as what medical practice is willing to accept. The available medical science demonstrates that there are more possibilities,24-26 but medical practice ignores or dismisses them.

27-29

However, this ignoring is not proper because there are patientcounterexamples.30-32

The RCP Curriculum does not refer to any possibility of ddeficiencies of iron, ferritin,33-36 B12,37 vitamin D3,38 folate,39,40 magnesium,41 copper, 42,43

Zinc,44,45 as common causes of patients with residual symptoms, or that sleep apnoea,46 depression,47 adrenal insufficiency,48 relative adrenal insufficiency,49 Candida albicans,50 pre-diabetes (or diabetes),51 or undiagnosed coeliac disease should be investigated.52 Neither does it mention other possible causes such as failure of the mitochondria, 53 or Euthyroid hypometabolism.4,5

Ideally, when such tests are undertaken, there is only one cause left, and that cause is treated. If there are none, the list of potential causes should be checked for completeness. Failure to address these issues is a failure to meet the diagnostics standard of care, yet over a quarter of a million sufferers in the UK remain dissatisfied with the way they feel. They are told their blood tests (often only TSH is measured) are ‘normal’, and that their symptoms are ‘not specific’, or due to depression, over-eating, or they have some other patient-blaming condition.

Because of the curriculum failure and endocrinology’s acceptance of ‘non-specific’ symptoms, patients are prescribed Prozac for depression; Amitriptyline for fibromyalgia; anti-inflammatories for musculoskeletal pain; oral contraceptives for irregular menses; low levels of antibiotics for acne; Viagra for loss of libido; Ritalin for ADD; Allopurinol for gout; and/or Lipitor for high cholesterol and others, too numerous to mention here. These prescriptions are costing the DoH millions of pounds and places a heavy burden of responsibility on the NHS.

The RCP admits that “Patients with continuing symptoms after appropriate thyroxine treatment should be further investigated to diagnose and treat the cause,15 but the curriculum FAILS to indicate what tests should be done to carry out these further investigations.

The RCP have made no attempt to evaluate the available scientific evidence regarding diagnostics and therapy, the use of T3 or natural thyroid extract for those patients who do not do well on T4 monotherapy. This wholesale dismissal of the available scientific evidence, amounts to medical negligence.54-149

Our opinion is that the RCP’s and the Endocrinology Establishment’s view of the greater thyroid system, is too narrow. TPA has produced, in association with a US Researcher, a Table (see Appendix ‘A’). This begins with the familiar hypothalamus-pituitary-thyroid gland axis and extends through peripheral conversion sites, peripheral cellular hormone receptors, and the peripheral cells, with support from the adrenals and the elimination of waste.  Whilst it is not the

whole answer to the problem of education, we believe it is a starting point and would welcome the RCP incorporating this in to its curriculum.

This problem is further exacerbated by the ‘Thyroid Function Testing Guidelines (July 2006)’, BTA, Assn of Clinical Biochemists’ (ACB) and British Thyroid Foundation (BTF),150 which also ignores a basic protocol of medicine - differential diagnosis. The Guidelines appear to assume that peripheral metabolism and peripheral hormone reception functions never fail, thereby ignoring all other potential causes of the symptoms. TPA believes that this may, in part, be due to the imprecise language currently used in describing ‘hypothyroidism’ (see heading Imprecise Language).

The RCP is offering little in the way of credible evaluation of the available scientific evidence, or the use of Liothyronine (T3) and/or Natural Thyroid hormone for those patients failing on T4 monotherapy.

Endocrinology Fails Patients with Symptoms of Hypothyroidism

There are no official Guidelines in the UK relating to the diagnosis and treatment of sufferers from symptoms of hypothyroidism. Instead, doctors are forced to rely on consensus statements drawn up by an independent panel of experts. All grading systems, including the World Health Organisation (WHO), place consensus statements and expert opinion by respected authorities, as the poorest level of evidence, because they have failed to recognise new concepts and treatments, based on up to date research as published in the medical literature. 150-156

A recent example of this was when the British Thyroid Foundation (BTF) teamed up with ‘NHS Choices’ to present an Online Clinic on Thyroid Disorders, (January 2012),157 which turned out to be a fiasco. The panel of experts (drawn from members of the British Thyroid Association (BTA)) became overwhelmed by the sheer volume of questions, and were unable to enter into any debate with questioners - as befits a forum. The online clinic served only to confirm the opinion held by this charity, that inadequate training is resulting in poor, or no diagnosis or correct treatment for over a quarter of a million patients in the UK. This view was corroborated by Dr Kerbel (GP representative for the British Thyroid Foundation),157 who apologised for “the poor deal patients are getting and admitted “there is still a lot of substandard practice around because of a problem with training & education, and that it is not only knowledge that’s lacking – it’s experience, training and learning how to manage what is a complex, difficult, and challenging condition”.

It is TPA’s belief that the problem of lack of knowledge and training, but perhaps not the extent of it, has been known about for some considerable time. However, the Royal College of Physicians (RCP), the General Medical Council (GMC), the BTA and the Endocrinology speciality as a whole, have failed to address this, thereby causing unnecessary suffering and real harm to patients, failed by inadequate diagnostics and the correct thyroid hormone therapy.

Imprecise Language

‘The Linguistic Etiologies of Thyroxine-resistant Hypothyroidism’,158 by E. Pritchard, published by Thyroid Science, addresses a very grave mistake that doctors and researchers make in developing the concepts of hypothyroidism and thyroid hormone therapy.

A logical examination of a continuing medical education course,159 and the Medical Practice Guidelines for Hypothyroidism,160-167 finds that they are not clear. 158

There is a total lack of appreciation of the two physiologically different definitions of ‘hypothyroidism’, believed to be equivalent prior to 1967. The RCP and the BTA definitions are not equivalent

The RCP (London) defines hypothyroidism as: "The clinical consequences of insufficient secretion by the thyroid gland"

This is the correct and narrow definition, which can, hopefully, be treated with T4-only medication.

The BTA defines hypothyroidism as "The clinical consequences of insufficient levels of thyroid hormones in the body"

In our opinion, the broad symptom-oriented BTA definition should therefore not be called Hypothyroidism. Taber’s Cyclopedic Medical Dictionary suggests that deficiencies in the hypothalamus-pituitary-thyroid axis, plus the potential deficiencies in the peripheral metabolism and peripheral hormone reception, which are recognised by science, and named “Euthyroid Hypometabolism”(EH).

The BTA broad definition fails to provide any diagnostic tools or therapy recommendations for those with impaired cellular response to thyroid hormone. The T4-only therapy is decidedly NOT applicable to EH, and may even be questionable treatment for those with symptoms of hypothyroidism.4 ,5

In 1997, endocrinologists attempted to correlate the classical symptoms and physical findings associated with hypothyroidism with modern thyroid blood tests. This was the first study in almost 30 years in which doctors attempted to demonstrate the clinical efficacy of thyroid function tests. Results were published in the Journal of Clinical Endocrinology:

“It is of special interest that some patients with severe biochemical hypothyroidism had only mild clinical signs, whereas other patients with minor biochemical changes had quite severe clinical manifestations. Thus, we assume that tissue hypothyroidism at the peripheral target organs must be different in an individual patient. Therefore, the clinical score can give a valuable estimate of the individual severity of metabolic hypothyroidism”.168

This is an excellent illustration of EH, without the authors even being aware of it.

There is no doubt of the existence of peripheral hormone and peripheral metabolism of T4 to T3. There are many readily available references. EH seems relatively common, yet Endocrinology appear to be unaware of its existence.

Note that Thyroid Hormone Resistance (THR) is a rare condition169 and is physiologically different to EH and the two must not be confused.4,5

The RCP must either disclaim peripheral thyroid hormone deficiencies, or explain their diagnostics and their proper therapy.

The reality of medical science and the need for linguistic care has yet to penetrate the hypothyroidism guideline/statement authorship committees. The RCP web site sets out their Clinical Guideline Standards.170

There is an urgent need for the RCP to indicate which Guideline Standard was used for the statement on the Diagnosis and Management of Primary Hypothyroidism.170

If the language used to describe these conditions was precise, this problem would disappear. If Endocrinology continues with its ambiguity, those patients with continuing symptoms will be doomed to continue with their suffering.

Liability under the Law of Torts

The Law of Torts requires inter alia that individuals, or organisations, in this case - the RCP, should “know or should have known”171 of the available evidence and current scientific knowledge in order to issue guidance which would not lead to tortfeasance, resulting in harm to patients. By ignoring all of the following, the RCP policy statement demonstrates numerous tort liabilities.  

It is the opinion of TPA that those quarter of a million patients being left to endure the symptoms of hypothyroidism, and who are not being afforded appropriate treatment, can be described as having suffered through the tortious acts of the RCP, BTA et. al., and should be liable for compensation through the courts.

The RCP and BTA have:

1. Ignored warnings in medical science of the failure of T4 monotherapy. (Kirk & Kvorning, 1947),172 (Means, 1954);173 (Baisier et al., 2001).174

2. Ignored the greater activity of T3 over T4. (Gross & Pitt-Rivers, 1953).175

3. Ignored the potential for euthyroid hypometabolism (Goldberg, 1960).4,5

4. Ignored the physiology discovered by (Refetoff, 1957176 and Braverman 1970)177 that connects the thyroid gland to the peripheral, symptom-producing cells.

5. Ignored the 14% of those treated with T4 monotherapy who are dissatisfied with their treatment (Saravanan, 2002).178

6. Ignored the long term study showing the failures of endocrinology to mitigate the symptoms of hypothyroidism (Baisier, Hertoghe, and Eeckhaut, Circa 2001)174 that showed better clinical and laboratory diagnostics treating patients with T3.

7. Ignored the existence of numerous subsequent studies on the characteristics of peripheral conversion or metabolism of T4 to T3, and peripheral cellular hormone reception functions.54-149

8. Ignored patient counterexamples to T4-only therapy where successful treatment with T3 has been achieved.179

9. Ignored findings showing that intracellular chemistry depends upon T3, not T4.4,5

10. Ignored demands of differential diagnostic protocol.17

11. Ignored linguistic and logical standards of care.158

12. Ignored the very common syndrome of thyroid and adrenal deficiency.48-49 using observation and medicine practised as an art.180 as the primary diagnostic method, with the laboratory playing a secondary role.

13. Ignored the science showing the above syndrome has global effects

14. 181 with imbalance of other hormones, the likely presence of systemic candida and dysbiosis, malabsorption and food allergy, all playing a probable role.

15. Ignored their Duty of Care.182

Proof exists that the BTA and RCP have:

1. Established the fiction that T3 is universally ineffective. (Various anti-T3 studies and meta-analyses, circa 2000-2006)

2. Effectively banned all T3 therapies from consideration for treatment for those who need it.

And by the above, plus maintenance of the above negligence, in spite of “knowing or should have known”, Endocrinology continues to condemn a quarter of a million patients to a miserable existence.

RCP and BTA Adherence to False Statements

The RCP stance is that they do not support the use of natural thyroid extract or Liothyronine (T3) without further validated published research. TPA is puzzled by this stance as there is no validated research published to show that T4 replacement is safe and effective for all patients. Studies show that for many people, T4 is harmful by virtue of its ineffectiveness, therefore, the proposition that T4 is safe and effective for all patients is false.183-192

The RCP and the BTA have long claimed that T4 monotherapy is effective for most hypothyroid patients. Of four T4 versus T4/T3 studies published in 2003, T4 replacement was found to be ineffective for many hypothyroid patients.193,p.14

At that time, at least six other studies had shown this to be true.194-200

Absent a clear duty of candour, the linguistic abuse will continue to sour relations between doctors and patients; misrepresentation of T3 as an inactive hormone, whilst maintaining that T4 is active is a nonsense.

The ‘AGREE’ Collaboration Appraisal of Guidelines and Evaluation Instrument 201 provides a validated, internationally agreed framework for assessing the quality of clinical practice guidelines. All recommendations should be linked to a list of references on which it is based. The RCP policy statement fails to supply these references, rendering it invalid.

Three years ago, a ‘new’ RCP report - ‘Innovating for Health’,202 found that patients:

• “Are worried about obtaining access to the most effective medicines to treat their particular needs.

• Want doctors to be free to prescribe the most effective drug based only on clinical need.

• Would like more choice, including choice between generic and branded alternatives in the same drug class.

• Are concerned that cost may be more important than efficacy in prescribing or access to medicines decisions.

• Wished that national decisions to make drugs available were uniformly honoured at local level.

A UK-wide medicines strategy would be able to address these issues, with the creation of a new Medicines Technical Advisory Group (MTAG), involving the medical profession, the pharmaceutical industry, regulators and patient organisations. The joint working strategy would pool untapped expertise across many organisations. It could defuse conflict, provide a forum for constructive discussion, enhance transparency and build trust.”

TPA would greatly welcome such a strategy.

Statements on BTA’s web site,203 which the RCP endorses, that synthetic T3/T4 and Armour Thyroid (and by extension, Erfa ‘Thyroid’, Nature Throid and Westhroid) work no better than T4 monotherapy, are also presented as fact, but are not substantiated.

These statements have contributed to the belief, endemic within Endocrinology, that T3 is of no use and this alone has probably caused more suffering and dysfunction than any other blunder in the history of medicine. Scientific facts patently show the falsity of those statements.204

Failure of the RCP to take account of research constitutes a fraud.

Dr John Lowe repeatedly asked the BTA Executive Committee to respond to specific points in a rebuttal he wrote to those statements, but received only an acknowledgment from Dr Allhabadia, promising further consideration of the matter after consultation with the RCP.205

This consultation has not yet happened and should be arranged as a matter of urgency, with a view to either amending the BTA’s statements, or removing them.

The Department of Health and doctors are, without question, accepting that the RCP’s and BTA’s statements are scientifically accurate, leading them into making decisions on behalf of patients that adversely affect their health and well-being.

The BTA mentions clinical trials in their statement that directly bear on its conclusions, but fail to cite any of these. The medical literature contains at least twenty two reports of studies in which researchers compared the effectiveness and safety of different thyroid hormone therapies.206-218

Among the therapies compared in the studies were T4 monotherapy, desiccated thyroid, and combined synthetic T4/T3. Instead of referencing these studies, however, the Committee cited only two papers in which authors reviewed the most recent studies that compared T4 monotherapy to synthetic T4/T3. One of those papers is a review of the studies by Escobar- Morreale et al.,185

and the other is a report of a meta-analysis by Grozinsky-Glasberg et al.195 (see Appendix ‘B’).

These two publications deal with synthetic T4/T3 therapies only and should NOT have been included in the BTA statement on Armour versus T4-only therapy.

Both contain factual errors and unbalanced presentations of data, excluding, or limiting data, favourable to T4/T3 therapies. Specific examples of these errors are included in Dr Lowe’s rebuttal.196

Maintaining the T4 monotherapy, even for patients with continuing symptoms, as Grozinsky-Glasberg, et al. 195 recommend, has the effect of weakening patients with continuing symptoms, since they do reflect the reduction in the patient’s natural ability to fight disease, particularly life’s great killers, diabetes and heart disease.

The RCP, the Executive Committee of the BTA, Escobar-Morreale et al., and Grozinsky-Glasberg et al. should correct their false statements of fact as well as their unbalanced presentations of data relevant to their conclusions. 

Patients have the right to benefit from medical practice guidelines/policy statements that are scientifically correct, linguistically precise, logically consistent, with no loose ends, and no overstatements.

Defective T4/T3 Studies

The RCP claim that the only evidence in all of the related medical science is 11 randomised clinical trials that compare a T4 monotherapy with a combination T4/T3. This is so ludicrous that such a statement cannot be taken seriously.

In the T3 -T4 meta-analysis, the authors found 501 papers and rejected 490, claiming they were not based upon randomised controlled trials.  So effectively, they ignored 98% of the available and relevant medical science on this pseudo scientific basis.

There is also disparity in the meta-analysis between the context 219

(“In some patients symptoms of hypothyroidism persist despite therapy

with T4”)

and the conclusion 219

(“T4 monotherapy should remain the treatment of choice for clinical hypothyroidism”). Meaning those with continuing symptoms on T4 monotherapy must continue to suffer.

Fewer than 1000 patients were studied, out of potentially millions world-wide. Therefore, these studies, by inductive logic, are subject to counterexamples. TPA has just under 2000 counterexamples to T4 monotherapy.14

An important factor in the design of the studies is the choice of subjects. The subjects had identified thyroid gland issues and were substantially already satisfied with their therapy. This substantially precluded those afflicted with impaired cellular response to thyroid hormone.

The subject selection of the anti-T3 studies were largely those with:

• Thyroid gland destruction or removal as compared with the recent pro -T3 study which had no such subjects.

• They were doing well on T4 monotherapy.

• The therapeutic value of the substituted T3 for the reduction in T4 was less per a National Institute of Health (NIH) study.

• The statistical method ignored low rate occurrences.

So the studies are defective and not representative of the reality of those with deficient peripheral metabolisms or increased peripheral hormone receptor resistance. The flaws in those study are; the choice of subjects; the choice of therapies; the statistics; and the over-conclusions. Given the low occurrence rates, they should have been looking for exceptions and not averages.

The second issue is the comparison. The focus on the thyroid gland suggests in the literature, a 14 to 1 exchange because that is the ratio of T4 to T3 in the thyroid gland.  Some studies used other ratios, like 10:1 or 5:1.  However, according to Celi,220 the relative therapeutic value is 3:1.  So the subjects were under treated when on the T4/T3 combination. Also, the T3 dosage levels were quite low, generally below the starting dose for adults (not children or seniors). And then the statistical averaging makes any improvement appear negligible.

 

Using subjects with primary hypothyroidism is not representative of subject’s deficient peripheral metabolism or increased peripheral hormone receptor resistance. They are physiologically different.

It is long past the time when these defective studies must be investigated.

Confirming Studies

Almost ten years ago, laboratory experts, and a committee of the nation's top endocrinologists issued recommendations to narrow the TSH reference interval so

that the high is 2.5 to 3.0, versus 5.0 to 5.5. Since then, there has been study after study linking subclinical/mild/borderline hypothyroidism to a host of health risks, including infertility, diabetes, high cholesterol, and heart disease. A recent meta analysis for over 55,000 subjects, from 11 studies showed that Subclinical hypothyroidism is associated with an increased risk of cardiovascular events and mortality - particularly if TSH is 10mIU/L or over.221

So, why are the RCP and BTA failing to produce the scientific evidence to show that the nation’s top endocrinologists are wrong, and that the RCP recommended TSH reference interval of 0.5 to 10.0 is correct? No such evidence exists! The RCP and BTA recommended TSH ref. interval is unmatched anywhere else in the world.

In another follow up study of 15,106 subjects,222 it was found that TSH within the reference range is positively and strongly associated with the risk of future hypothyroidism. TSH at the lower limit of the reference range may be associated with an increased risk of hyperthyroidism.

The recommended treatment of T4 monotherapy, more often than not, fails to recognise that not everybody is able to convert sufficiently to the active T3

Joffe et al, (1985);223 Cooke et al, (1992);224 Gelenberg, (1992);225

Dommisse, (1993);226 Whybrow, (1994);227 nor in laboratory rats, Escobar-Morreale et al, (1996).68 Routine measurement of free T3, whenever screening for, or monitoring treatment of those patients with symptoms of hypothyroidism, will quickly confirm this. But, the RCP and the BTA continue with their denial! This makes a mockery of their standards.

There are also signs of dissatisfaction amongst medical practitioners concerning T4 monotherapy, as reflected in the papers by Chopra (1997),228 DeGroot (1999),229 Ridgway, Canaris, et al. (2000)230 and O’Reilly (2000).231

Still further evidence of the shift toward including T3 is provided by another paper: The multi-centre Italian 'Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism' reported that "both fT4 and fT3 serum levels ... are necessary for a more accurate disclosure of over- or under-treated patients." (Ferretti et al, 1999).232 The RCP have disregarded these studies – which again, makes a mockery of their standards.

The RCP and DoH has also disregarded the results of a survey of hypothyroid patients undertaken by TPA in 2005-2006. This survey highlights the dissatisfaction of many patients. This survey has very good credentials in that it points to inconsistencies within the data presented by the RCP and the BTA as being 'definitive'. This hypothyroid patient survey should be held up as valid, contradictory evidence to the RCP policy statement. This makes a mockery of their standards!

Of 1500 respondents to this survey, when asked of those undergoing L-thyroxine -only therapy, “Do you feel that you have fully regained your optimal state of health?” 1176 (78.4%) answered “NO”. 233

Counterexamples to T4-only Therapy

A responsible scientist, finding a counterexample to his idea must limit or abandon his idea as unreliable. 

TPA is in the process of collating a ‘Register of Counterexamples to T4 Monotherapy’.234 A component of the register is the patients’ willingness to testify. This survey is applicable to those who continued to suffer symptoms on T4 monotherapy and who found those symptoms were mitigated or disappeared when they began T3 hormone therapy.

With the registering of just under 2000 counterexamples to T4 monotherapy (March 2012) and with the philosophy of science, described by Sir Karl Popper, TPA have irrefutable proof that Endocrinology’s stance is dangerously wrong and that it’s continuance of practising in line with the T4 monotherapy diktat for all sufferers of the symptoms of hypothyroidism is pernicious.

TPA is currently investigating the existence of triple counterexamples hidden in the Register because they have the experience that comport with the test protocol Challenge, De-challenge, Re-challenge (CDR).235

Further, triple counterexamples provide causation proof for the value of T3.

As currently delineated, which is not good even by medicine's standards, the medical evidence for the support of the universal virtual ban on all T3-containing hormone replacements is illogical, unethical and nonsensical, and would not be admitted as evidence, because counterexamples demonstrate its lack of reliability. 

Autonomy of Medical Professionals

The RCP has taken away the right for medical practitioners to exercise their professional clinical judgement.236

According to the ‘Medicines and Healthcare Regulatory Agency (MHRA) Review of Unlicensed Medicines’, they make the point that: “Clinicians should have the ability in appropriate circumstances to exercise their professional judgement to commission the supply of an unlicensed medicine to meet the special needs of an individual patient”.237

Taking away a doctor’s autonomy makes the RCP policy statement mandatory. The law is not fond of unresolved issues and will follow the generally accepted interpretation. The present case is the boycotting of all alternatives to levothyroxine sodium. The doctor who dares defy the medical guidelines for the benefit of the patient can find him/herself in substantial and costly disciplinary difficulties with the GMC, even if the doctor is treating his patient ethically and scientifically.

So doctors are fearful of the RCP’s influence upon the GMC. They fear losing their career and livelihood should they dare to diagnose or treat outside of this policy statement, which goes beyond the bounds of primary hypothyroidism. Fear of prosecution enforces compliance. Compliance stops them diagnosing and treating their patients properly. The RCP policy statement, because it goes beyond the bounds of primary hypothyroidism, is harming patients and doctors.

References

1. Joint Committee on Higher Medical Training, “Higher Medical Training Curriculum for Endocrinology and Diabetes Mellitus,” 2003, 5 Saint Andrews Place, Regent’s Park, London NW1 4LB

2. Good Medical Practice: Teaching and training, appraising and assessing.

3. Map of Medicine: Royal College of Physicians Joint specialty societies.

4. Goldberg M, The Case For Euthyroid Hypometabolism, Am J Med Sc October, 1960 pgs 479-493

5. Goldberg M, Diagnosis of Euthyroid Hypometabolism, Am J Obst & Gynec, 81(5): 1053-1058, 1961

6. Baisier, WV, Hertoghe, J., Beekhaut, W., Thyroid Insufficiency? Is Thyroxine the Only Valuable Drug?, Journal of Nutritional and Environmental Medicine, Vol. 11, No. 3, September 2001, pages 159-166

7. Braverman LE, Ingbar SH, Keinwem S, Conversion of Thyroxine (T4) to Triiodothyronine (T3) in Athyreotic Human Subjects, The J Clin Invest, 1970

8. Danzi S, Ojamaa K, and Klein I, Triiodothyronine-Mediated Myosin Heavy Chain Gene Transcription in the Heart, Am J Phys Heart Circ Physiol, Feb 27, 2003

9. Eisenstein Z, Hagg S, Braverman LE, et al., Effect of Starvation on the Production and Peripheral Metabolism of 3,3',5' Triiodothyronine in Euthyroid Obese Subjects, J Clin Endocrinol Metab, 1978, 47(4): 889-893

10. Nomura S., et al. Reduced Peripheral Conversion of Thyroxine to Triiodothyronine in Patients with Hepatic Cirrhosis, J of Clin Invest, Sept 1975, 56(3): 643-652

11. Refetoff S, Dewind LT, DeGroot LJ, Familial Syndrome Combining Deaf-mutism, Stippled Epiphyses, Goiter and Abnormally High PBI: Possible Target Organ Refactoriness to Thyroid Hormone, J Clin Endocrinol Metab, 27:279, 1967

12. Refetoff S, Weiss RE, Usala SJ, The Syndromes of Resistance to Thyroid Hormone, Endocr Rev, 1993, 14(3):348-399

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14. Thyroid Patient Advocacy sponsored a registry of counterexamples, numbering just under 2000 (Mar. 2012).

15.

16. Saravanan P, Chau F, Roberts N, Vedhara K, Greenwood R, Dayan CM, 2002, Psychological Well-Being in Patients on "Adequate" Doses of L-Thyroxine Results of a Large, Controlled Community-Based Questionnaire Study, Clinical Endocrinology, 2002, 57: 577-585

17. Robert H. Seller, MD and Andrew B. Symons, MD, MS ‘Differential Diagnosis of Common Complaints’, 6th Edition. ISBN: 9781455707720

18. Differential Diagnosis (DDX) Definition: “The distinguishing of a disease or condition from others presenting with similar signs and symptoms,” Merriam-Webster

19. Differential Diagnosis (DDX) ”is a systematic method used to identify unknowns. This method, essentially a process of elimination, is used by taxonomists to identify living organisms, and by physicians and other qualified professionals to diagnose the specific disease in a patient. Not all medical diagnoses are differential ones: some diagnoses merely name a set of signs and symptoms that may have more than one possible cause, and some diagnoses are based on intuition or estimations of likelihood.” Wikipedia:

20. Differential Diagnosis is a medical adaption of the process of elimination. These processes are based upon the logic of disjunctive syllogism, which is known from antiquity as modus tollendo poner

21. Geisler NL, Brooks RM, Come, Let Us Reason, Baker Book House, original printing 1990

22. A. P. Weetman. Whose Thyroid Hormone Replacement is it Anyway? Clin Endocrinol. 2006;64(3):231-233. 

23. Sharpe M, Carson A, “Unexplained Somatic Symptoms, Functional Syndromes, and Somatization: Do We Need a Paradigm Shift?, Ann Intern Med, 2001, 134:926-930

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31. Baisier, WV, Hertoghe, J., Beekhaut, W., Thyroid Insufficiency? Is Thyroxine the Only Valuable Drug?, Journal of Nutritional and Environmental Medicine, Vol 11, No. 3, September 2001, pages 159-166

32. Turner S. Patient Counterexample Registry, Thyroid Patient Advocacy

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58. Hertoghe T. Many conditions related to age reduce the conversion of thyroxine to triiodothyronine - a rationale for prescribing preferentially a combined T3 + T4 preparation in hypothyroid adults. Anti-Aging Medical Therapeutics 2000; IV: 138-53 T3-T4 (and T3) treatments work better than T4

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62. Pareira VG, Haron ES, Lima-Neto N, Medeiros-Neto GA. Management of myxedema coma: report on three successfully treated cases with nasogastric or intravenous administration of triiodothyronine. J Endocrinol Invest. 1982;5:331-4

63. Chernow B, Burman KD, Johnson DL, McGuire RA, O'Brian JT, Wartofsky L, Georges LP. T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model. Crit Care Med. 1983 Feb;11(2):99-104

64. Arlot S, Debussche X, Lalau JD, Mesmacque A, Tolani M, Quichaud J, Fournier A. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med. 1991;17(1):16-8 T3-T4 treatment: adding T3 to T4 results in greater improvement of clinical symptoms and signs in hypothyroid patients

65. Benevicius R, Kazanavicius G, Zalinkovicius R, Prange AJ. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med.1999; 340: 424-9.

When T3 and T4 are both supplemented to the food simultaneously with goitrogens, a much better prevention of goiter is obtained than when solely T4 is added, even if T4 is given at doses 7 times higher those of T3-T4 treatments

66. Devlin WF, Watanabe H. Thyroxin-triiodothyronine concentrations in thryoid powders. J Pharm Sci. 1966 Apr;55(4):390-3

In humans, T4-T3 treatments reduce serum cholesterol and increase the speed of the Achilles tendon reflexes better than T4 treatments alone

67. Alley RA, Danowski TS, Robbins T JL, Weir TF, Sabeh G, and Moses CL. Indices during administration of T4 and T3 to euthyroid adults. Metabolism. 1968;17(2):97-104

A study in rats rendered hypothyroid shows that cellular euthyroidism is only obtained in the target organs of hypothyroid rats if T3 is added to the classic T4 medication

68. Escobar-Morreale HF, del Rey FE, Obregon MJ, de Escobar GM. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology. 1996 Jun;137(6):2490-502

69. Escobar-Morreale HF, Obregon MJ, Escobar del Rey F, Morreale de Escobar G. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J Clin Invest. 1995 Dec;96(6):2828-38

Medications with T4 alone do not succeed in achieving complete cellular euthyroidism in the target organs, probably because T3 is really the active hormone

70. Asper SP Jr, Selenkow HA, and Plamondon CA. A comparaison of the metabolic activities of 3,5,3’-triiodothyronine and l-thyroxine in myxedema. Bull John Hopkins Hosp. 1953; 93: 164

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72. Gross J, Pitt-Rivers R. Physiological activity of 3:5:3'-L-triiodothyronine. Lancet. 1952 Mar 22;1(12):593-4

T3 is much more potent than T4

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Conditions that reduce the conversion of T4 to T3 such as aging, obesity, disease, stress, exercise, malnutrition, etc., reducing thereby the efficacy of a T4 alone treatment

74. Burroughs V, Shenkman L. Thyroid function in the elderly. Am J Med Sci. 1982, 283 (1): 8-17

75. Carter JN, Eastman CJ, Corcoran JM, and Lazarus L. Inhibition of conversion of thyroxine to triiodothyronine in patients with severe chronic illness. Clin Endocrinol. 1976; 5: 587-94

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77. Katzeff HI, Selgrad C. Impaired peripheral thyroid hormone metabolism in genetic obesity. Endocrinology. 1993; 132 (3): 989-95

78. Croxson MS and Ibbertson HK. Low serum triiodothyronine (T3) and hypothyroidism in anorexia nervosa. J Clin Endocrinol Metab. 1977; 44: 167-73

79. Harns ARC, Fang SH, Vagenakis AG, and Braverman LE. Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. Metabolism. 1978;27(11):1680-90

80. Opstad PK, Falch D, Öktedalen O, Fonnum F, and Wergeland R. The thyroid function in young men during prolonged physical exercise and the effect of energy and sleep deprivation. Clin Endocrinol. 1984; 20: 657-69

81. Walfish PG. Triiodothyronine and thyroxine interrelationships in health and disease. Can Med Ass. J 1976, 115: 338-42

Toxic substances such as phenols, cadmium, mercury, etc, and medications such as propranolol, amiodarone and several others may interfere by stimulating or inhibiting the T4 to T3 conversion

82. Feyes D, Hennemann G and Visser TJ. Inhibition of iodothyronine deiodinase by phenolphtalein dyes. Fed Eur Biomed Sci. 1982; 137(1):40-4

83. Bahn AK, Mills JL, Snyder PJ, Gann PH, Houten L, Bialik O, Hollmann L, and Utiger RD. Hypothyroidism in workers exposed to polybrominated biphenyls. N Engl J Med. 1980; 302: 31-3

84. Ikeda T, Ito Y, Murakami I, Mokuda O, Tominaga M and Mashiba H. Conversion of T4 to T3 in perfused liver of rats with carbontetrachloride-induced liver injury. Acta Endocrinol. 1986;112: 89-92

85. Paier B, Hagmüller K, Nolli Mi, Gonzalez Pondal M, Stiegler C and Zaninovich AA. Changes induced by cadmium administration on thyroxine deiodination an

86. Barregärd L, Lindstedt G, Schütz A, Sällsten G. Endocrine function in mercury exposed chloralkali workers. Occup Envir Med. 1994; 51: 536-40

Deficiencies in hormones (T3 itself, TSH, growth hormone, insulin, melatonin, etc) and trace elements (selenium, iron, zinc, cupper, etc) partially block this essential step for thyroid function

87. Burger AG, Lambert M, Cullen M. Interférence de substances médicamenteuses dans la conversion de T4 en T3 et rT3 chez l’homme. Ann Endocrinol (Paris). 1981,42:461-9

88. Grussendorf M, Hüfner M. Induction of the thyroxine to triiodothyronine converting enzyme in rat liver by thyroid hormones and analogs. Clin Chim Acta. 1977;80:61-6

89. Erickson VJ, Cavalieri RR, Rosenberg LL. Thyroxine-5’-diodinase of rat thyroid, but not that of liver, is dependent on thyrotropin. Endocrinology. 1982;111:434-40

90. Rezvani I, DiGeorge AM, Dowshen SA, Bourdony CJ. Action of human growth hormone on extrathyroidal conversion of thyroxine to triiodothyronine in children with hypopituitarism. Pediatr Res. 1981;15:6-9

91. Schröder-Van der elst JP, Van der heide D. Effects of streptozocin-induced diabetes and food restriction on quantities and source of T4 and T3 in rat tissues. Diabetes. 1992;41:147-52

92. Gavin LA, Mahon FA, Moeller M. The mechanism of impaired T3 production from T4 in diabetes. Diabetes. 1981;30:694-9

93. Hoover PA, Vaughan MK, Little JC, Reiter RJ. N-methyl-D-aspartate does not prevent effects of melatonin on the reproductive and thyroid axes of male Syrian hamsters. J Endocrinology. 1992;133:51-8

94. Chanoine J-P, Safran M, Farwell AP, Tranter P, Ekenbarger DM, Dubord S, Alex s, Arthur JR, Beckett GJ, Braverman LE, Leonard JL. Selenium deficiency and type II 5’-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine. Endocrinology. 1992;130:479-84

95. Arthur JR, Nicol F, Beckett GJ. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr Suppl. 1993; 57:236S-9S

96. Beard J, Tobin B, and Green W. Evidence for thyroid hormone deficiency in iron-deficient anemic rats. J Nutr. 1989;772-8

97. Fujimoto S, Indo Y, Higashi A, Matsuda I, Kashiwabara N, and Nakashima I. Conversion of thyroxine into triiodothyronine in zinc deficient rat liver. J Pediatr Gastroenterol Nutr. 1986;5:799-805

98. Olin KI, Walter RM, and Keen CL. Copper deficiency affects selenoglutathione peroxidase and selenodeiodinase activities and antioxidant defense in weanling rats. Am J Clin Nutr 1994;59:654-8

On the other hand, excesses in hormones (glucocorticoids, ACTH, estrogens,…) and trace elements (iodine, lithium, …) may slow down this conversion

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100. Heyma P, Larkins RG. Glucocorticoids decrease the conversion of thyroxine into 3,5,3’-triiodothyronine by isolated rat renal tubules. Clin Science. 1982; 62: 215-20

101. Scammell JG, Shiverick KT, Fregly MJ. Effect of chronic treatment with estrogen and thyroxine, alone and combined, on the rate of deiodination of l-thyroxine to 3,5,3’-triiodothyronine in vitro. Pharmacology. 1986;33: 52-7

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103. Voss C, Schrober HC, Hartmann N. Einfluss von Lithium auf die in vitro-Deioderung von l-Thyroxin in der Ratten leber. Acta Biol Med Germ. 1977; 36:1061-5

The absorption of oral T4 can be variable (50 to 73%), contrasting with that of T3 that is more constant and efficient (95%)

104. Hays MT. Absorption of oral thyroxine in man. J Clin Endocrinol Metab. 1968; 28 (6):749-56

105. Surks MI, Schodlow AR, Stock Jm, Oppenheimer JH. Determination of iodothyronine absorption and conversion of L-thyroxine using turnover rate techniques. J Clin Invest. 1973; 52:809-11

106. Hays MT. Absorption of triidothyronine in man. J Clin Endocrinol Metab. 1970; 30(5):675-6

Defects in the commercial T4 preparation

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108. Peran S, Garriga MJ, Morreale de Escobar G, Asuncion M, Peran M. Increase in plasma thyrotropin levels in hypothyroid patients during treatment due to a defect in the commercial preparation . J Clin Endocrinol Metab. 1997;82(10):3192-5

A lower serum T3 (and higher serum T4) is found in heart patients with arrhythmia

109. Selivonenko VG, Zaika IV. The function of the thyroid and thyrotropic function in patients with chronic ischemic heart disease and rhythm disorders. Lik Sprava. 1998 Jan-Feb;(1):81-3

110. Inama G, Furlanello F, Fiorentini F, Braito G, Vergara G, Casana P. Arrhythmogenic implications of non-iatrogenic thyroid dysfunction. G Ital Cardiol. 1989 Apr;19(4):303-10 (Hypothyroidism in patients with hyperkinetic ventricular arrhythmias (25%), atrial fibrillation (37.5%) and atrio-ventricular block (37.5%))

111. Vanin LN, Smetnev AS, Sokolov SF, Kotova GA, Masenko VP. Thyroid function in patients with ventricular arrhythmia. Kardiologiia. 1989 Feb;29(2):64-7 (Hyperthyroidism was diagnosed in 4.8% of 21 patients with persistent ventricular arrhythmias, and latent hypothyroidism was diagnosed in 38.1%)

112. Vanin LN, Smetnev AS, Sokolov SF, Kotova GA, Masenko VP. Study of thyroid function in patients with paroxysmal supraventricular tachycardia. Kardiologiia. 1989 Jan;29(1):71-4

113. Nesher G, Zion MM. Recurrent ventricular tachycardia in hypothyroidism--report of a case and review of the literature. Cardiology. 1988;75(4):301-6

114. Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of "torsade de pointe" type in hypothyroidism. Acta Med Scand. 1983;213(3):231-5

Low serum T3 and T4 levels are found in patients with coronary heart disease

115. Miura S, Iitaka M, Suzuki S, Fukasawa N, Kitahama S, Kawakami Y, Sakatsume Y, Yamanaka K, Kawasaki S, Kinoshita S, Katayama S, Shibosawa T, Ishii J. Decrease in serum levels of thyroid hormone in patients with coronary heart disease. Endocr J. 1996 Dec;43(6):657-6

A low serum free T3 in patients with coronary bypass increases the risk of postoperative atrial fibrillation (higher risk than that of not taking a beta-blocker)

116. Cerillo AG, Bevilacqua S, Storti S, Mariani M, Kallushi E, Ripoli A, Clerico A, Glauber M. Free triiodothyronine: a novel predictor of postoperative atrial fibrillation. Eur J Cardiothorac Surg. 2003 Oct;24(4):487-92

Progressively lower serum T3 levels are found in patients with ischemic heart disease form coronary stenosis to mycocardial infarct

117. Telkova IL, Tepliakov AT. Changes of thyroid hormone levels in the progression of coronary artery disease. Arteriosclerosis. Klin Med (Mosk). 2004;82(4):29-34

118. Pavlou HN, Kliridis PA, Panagiotopoulos AA, Goritsas CP, Vassilakos PJ. Euthyroid sick syndrome in acute ischemic syndromes. Angiology. 2002 Nov-Dec;53(6):699-707

119. Pimenov LT, Leshchinskii LA. Thyroid hormone changes (iodothyroninemia) in patients with acute myocardial infarction, and their clinical significance. Kardiologiia. 1984 Oct;24(10):74-7

Low serum free and total T3 (and low free T4 and high TSH) levels are found in patients suffering from acute mycocardial infarct with poor outcome

120. Satar S, Seydaoglu G, Avci A, Sebe A, Karcioglu O, Topal M. Prognostic value of thyroid hormone levels in acute myocardial infarction: just an epiphenomenon? Am Heart Hosp J. 2005 Fall;3(4):227-33

Auto-immune thyroidiits is associated with poorer heart indices

121. Zoncu S, Pigliaru F, Putzu C, Pisano L, Vargiu S, Deidda M, Mariotti S, Mercuro G. Cardiac function in borderline hypothyroidism: a study by pulsed wave tissue Doppler imaging. Eur J Endocrinol. 2005 Apr;152(4):527-33 (namely “impairment of systolic ejection, a delay in diastolic relaxation and a decrease in the compliance to the ventricular filling. Several significant correlations were found between the parameters and serum-free T(3) and T(4) and TSH concentrations. Data strongly support the concept of a continuum spectrum of a slight thyroid failure in autoimmune thyroiditis”)

Increased incidence of auto-immune thyroiditis and overt hypothyroidism in

men with acute mycocardial infarct, which may have contributed to the

development of the disease.

122. Cerillo AG, Bevilacqua S, Storti S, Mariani M, Kallushi E, Ripoli A, Clerico A, Glauber M. Free triiodothyronine: a novel predictor of postoperative atrial fibrillation. Eur J Cardiothorac Surg. 2003 Oct;24(4):487-92

A low serum T3 or T4 (hypothyroidism) is found in cardiac failure:

123. Khaleeli AA, Memon N. Factors affecting resolution of pericardial effusions in primary hypothyroidism: a clinical, biochemical and echocardiographic study. Postgrad Med J. 1982 Aug;58(682):473-6

124. Reza MJ, Abbasi AS. Congestive cardiomyopathy in hypothyroidism. West J Med. 1975 Sep;123(3):228-30

125. Rays J, Wajngarten M, Gebara OC, Nussbacher A, Telles RM, Pierri H, Rosano G, Serro-Azul JB. Long-term prognostic value of triiodothyronine concentration in elderly patients with heart failure. Am J Geriatr Cardiol. 2003 Sep-Oct;12(5):293-7 (“Lower serum T3 in cardiac failure: the odds ratio for events was 9.8 (95% confidence interval,2.2-43, p=0.004) for patients in the lowest tertile of triiodothyronine, that is, lower than 80 ng/dL, compared with patients with levels above 80 ng/dL”)

126. Pingitore A, Landi P, Taddei MC, Ripoli A, L'Abbate A, Iervasi G. Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am J Med. 2005 Feb;118(2):132-6

127. Klein I, Ojama K. In: Werner & Ingbar’s The Thyroid, ed. Braverman LE & Utiger RD, Lippincott-Raven Publishers, Philadelphia, 1996, 62: 799-804

A low serum free T3 index/reverse T3 ratio in chronic heart failure patient

is a highly significant predictor of poor outcome

128. Cerillo AG, Bevilacqua S, Storti S, Mariani M, Kallushi E, Ripoli A, Clerico A, Glauber M. Free triiodothyronine: a novel predictor of postoperative atrial fibrillation. Eur J Cardiothorac Surg. 2003

129. Hamilton MA, Stevenson LW, Luu M, Walden JA. Altered thyroid hormone metabolism in advanced heart failure. J Am Coll Cardiol. 1990 Jul;16(1):91-5

130. Kozdag G, Ural D, Vural A, Agacdiken A, Kahraman G, Sahin T, Ural E, Komsuoglu B. Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur J Heart Fail. 2005 Jan;7(1):113-8

A low serum T3 or T4 in heart patients is associated with an increased rise

of cardiac arrest/death

131. Wortsman J, Premachandra BN, Chopra IJ, Murphy JE. Hypothyroxinemia in cardiac arrest. Arch Intern Med. 1987 Feb;147(2):245-8

132. Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L'Abbate A, Donato L. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003 Feb 11;107(5):708-13

Thyroid therapy of cardiac patients

133. Corrective thyroid therapy is safe in hypothyroid patients with common benign cardiac arrhythmias at the condition that thyroid treatment is started at low doses and then gradually and prudently increased to the adequate dose. The treatment does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates

134. Polikar R, Feld GK, Dittrich HC, Smith J, Nicod P. Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias. J Am Coll Cardiol. 1989 Oct;14(4):999-1002

Thyroid therapy corrects the bradycardia of hypothyroidism

135. Yamauchi K, Takasu N, Ichikawa K, Yamada T, Aizawa T. Effects of long-term treatment with thyroxine on pituitary TSH secretion and heart action in patients with hypothyroidism. Acta Endocrinol (Copenh). 1984 Oct;107(2):218-24 (“T4 doses should be adjusted to maintain normal ET/PEP (systolic time intervals) rather than normal serum TSH levels”)

Thyroid therapy corrects the ventricular arrhythmia

136. Vanin LN, Smetnev AS, Sokolov SF, Kotova GA, Masenko VP. Thyroid function in patients with ventricular arrhythmia. Kardiologiia. 1989 Feb;29(2):64-7 (“Thyroid therapy for hypothyroidism led to the disappearance of paroxysms of ventricular tachycardia and reduced the total number and grades of ventricular extra-systoles in patients with ventricular arrhythmias; moreover, sensitivity to antiarrhythmic agents develop

Coronary heart disease in humans: the improvement with thyroid treatment ed to replace an earlier resistance”

137. Barnes BO. Prophylaxis of ischaemic heart-disease by thyroid therapy. Lancet. 1959 Aug 22;2:149-52

138. Holland FW 2nd, Brown PS Jr, Clark RE. Acute severe postischemic myocardial depression reversed by triiodothyronine. Ann Thorac Surg. 1992 Aug;54(2):301-5

139. Israel M. An effective therapeutic approach to the control of atherosclerosis illustrating harmlessness of prolonged use of thyroid hormone in coronary disease. Am J Dig Dis. 1955 June;161-8

140. Yokoyama Y, Novitzky D, Deal MT, Snow TR. Facilitated recovery of cardiac performance by triiodothyronine following a transient ischemic insult. Cardiology. 1992;81(1):34-45

Adequate thyroxine replacement in hypothyroidism prevents coronary artery disease progression

141. Perk M, O’Neill BJ; The effect of thyroid therapy on angiographic artery disease progression. Can J Card. 1997;13(3):273-6

Desiccated thyroid therapy improves cardiac failure refractory to digitalis in humans

142. Zondek H. Myxedema Heart. Munch Med Wochenschr. 1918, 65: 1180-3

143. Khaleeli AA, Memon N. Factors affecting resolution of pericardial effusions in primary hypothyroidism: a clinical, biochemical and echocardiographic study. Postgrad Med J. 1982 Aug;58(682):473-6

T3-therapy improves the outcome of open heart sugery, especially heart transplants

144. Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V. Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery. Cardiology. 1996 Nov-Dec;87(6):509-15.

145. Novitzky D, Cooper DK, Chaffin JS, Greer AE, DeBault LE, Zuhdi N. Improved cardiac allograft function following triiodothyronine therapy to both donor and recipient. Transplantation. 1990 Feb;49(2):311-6

Thyroid hormone therapy greatly reduces the lesions of experimental myocardial infarct in rats

146. Holland FW, Brown PS, Clark RE. Acute severe postischemic myocardial depression reversed by triiodothyronine. Ann Thorac Surg 1992 54: 301-305

Thyroid therapy reduces coronary artery disease and cardiac fibrosis in mice

147. Yao J, Eghbali M. Decreased collagen mRNA and regression of cardiac fibrosis in the ventricular myocardium of the tight skin mouse following thyroid hormone treatment. Cardiovasc Res. 1992 Jun;26(6):603-7

Thyroid therapy reduced the lesions of experimental cardiac arrest in dogs

148. Facktor MA, Mayor GH, Nachreiner RF, D'Alecy LG. Thyroid hormone loss and replacement during resuscitation from cardiac arrest in dogs. Resuscitation. 1993 Oct;26(2):141-6

Thyroid therapy reduced the complications of hemorrhagic shock in dogs

149. Shigematsu H, Shatney CH. The effect of triiodothyronine (T3) and reverse triiodothyronine (rT3) on canine hemorrhagic shock. Nippon Geka Gakkai Zasshi. 1988 Oct;89(10):1587-93.

150. UK Guidelines for the Use of Thyroid Function Tests (July 2006)

151. Amerling R, Winchester JF, Ronco C, “Guidelines have done more harm than good,”Blood Purification 2008;26;73-76.

152. Guirguis-Blake J, Calonge N, Miller T, Siu A, Teutsch S, Whitlock E., “Current processes of the U.S. Preventive Services Task Force: refining evidence-based recommendation development”. Ann. Intern. Med 2007; 147(2):117–22.

153. Barton MB, Miller T, Wolff T, et al. “How to read the new recommendation statement: methods update from the U.S. Preventive Services Task Force,” Ann. Intern. Med 2007;147(2):123–7.

154. CEBM > EBM Tools > Finding the Evidence > Levels of Evidence .

155. Atkins D, Best D, Briss PA, et al. (2004). “Grading quality of evidence and strength of recommendations,” BMJ 2004;328 (7454):1490.

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157. British Thyroid Foundation and NHS Choices:

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Royal College of Physicians Mission: “We will be relentless in our pursuit of improvements in healthcare and the health of the population. We will achieve this by enhancing and harnessing the skills, knowledge and leadership of physicians in setting challenging standards and encouraging positive change based on sound evidence”…

“Our historical mission of ensuring that medicine is practised to the highest standards remains almost entirely unchanged… Our strategic framework will ensure that we remain central to providing the best health services in the modern world”

A quote from a patient’s response to the International Hypothyroid Patient Petition238

“The ignorance, arrogance and incomprehension of the medical doctors I have been

subjected to in my search for diagnosis and treatment leaves me incandescent with

rage. Even as a qualified health professional working for a major DGH I remain

powerless to prevent the cumulative long term health risks associated with lack of

treatment; I am voiceless, neutered, patronised, and crawling day-to-day through what used to be my vital and colourful life. I would give everything I have for an open

minded and creative diagnostician, and more for a little compassion, but this seems to

be entirely beyond the capability of the modern medic. God help us all.”

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