This website is dedicated to the millions of thyroid patients who are being ignored and left to suffer unnecessarily, and to healthcare practitioners, who want to better serve those patients.

ENDOCRINOLOGY FAILURES HARMING APPROX. 300,000 UK PATIENTS


Anthony D Toft (past President of the Royal College of Physicians (RCP)) wrote: It is extraordinary that more than 100 years since the first description of the treatment of hypothyroidism and the current availability of refined diagnostic tests, debate is continuing about its diagnosis and management. This statement exemplifies the blinkered attitude which seems to be that medical practitioners know all they need to know about the diagnosis and management of those with symptoms of hypothyroidism, so that further research and debate are unnecessary. [BMJ2003;326:295]

Extraordinary indeed!

INTRODUCTION

There has been significant concern by health care organizations and medical experts that physicians are placing too much reliance on consensus statements and failing to learn of new information presented in medical journals. Thus, they lack the ability to translate this new information into treatments for their patients. The concern is that doctors fail to practice evidence-based medicine, erroneously relying on what they have previously been taught and on expert societies instead of changing treatment philosophies based on new information as it becomes available. This is especially true for endocrinological conditions, where physicians are very resistant to changing old concepts of diagnosis and treatment despite overwhelming evidence to the contrary because it is not what they were taught in medical school and endocrinology residency”[183]

AIMS

The aim of this paper is to draw attention to, and provide evidence of the harm being caused to approximately 300,000 UK citizens (around 15% of the population currently being treated for thyroid problems), who are left to suffer symptoms of hypothyroidism, because of current diagnosis and treatment methods employed by the UK s endocrinology specialty. The 300,000 figure is approximately 0.5% of the total population, whilst also being 15% of those treated for thyroid problems. This figure ignores euthyroid hypometabolism victims, which may represent 6% of the total population.

Thyroid Patient Advocacy (TPA) is demanding change, by asking the Government to arrange an open meeting between members of the Royal College of Physicians (RCP), the British Thyroid Association (BTA), the Department of Health (DoH) and members of patient representative organisations that stand in diametric opposition to the present RCP guidance statement on the Diagnosing and Management of Primary Hypothyroidism.

TPA represents tens of thousands of sufferers in the UK, but was not approached to give their views when the RCP policy statement was originally formulated, and has still never been approached.

This paper seeks to evidence that the need for corrective action is long overdue, so that symptoms of hypothyroidism attributable to the whole of the thyroid system are properly investigated and treated. It also criticises the RCP policy statement and seeks to highlight its errors, which are enforced by the General Medical Council (GMC). It further criticises the British Thyroid Association (BTA) statement on Armour Thyroid v L-T4 monotherapy, which, as this paper will evidence, fails to take into account scientific research that has been available for over half a century.

PLEASE NOTE: There is NO validated published research showing that L-T4 monotherapy is safe and effective for ALL sufferers of hypothyroid symptoms. Therefore, the proposition by the RCP and the BTA that L-T4 monotherapy is safe and effective for all sufferers CANNOT and MUST NOT be relied upon.

EVIDENCE

There are seven distinct causes of symptoms of hypothyroidism, that are attributable to the thyroid system:

– hypothalamus deficiencies
– pituitary deficiencies
– thyroid deficiencies
– conversion problems
– reception problems
– chemical infrastructure
– excessive clearance

Despite this, the RCP and the BTA only provide guidance on identifying and treating one cause of hypothyroidism (defined by the RCP as under-activity of the thyroid gland), and they only recognise one of its hormones – thyroxine (T4).

TPA believes that the RCP and BTA both have serious omissions in their statements, resulting in a violation of the requirements laid down by the GMC. This is because they make no reference to peripheral metabolism or peripheral hormone receptor physiology. This is particularly worrying, given that the RCPs remit is education and maintenance of professional standards for physicians, and further to this, the BTA claims they are … the only national professional organisation in the UK composed of research doctors and consultants who are accredited by having completed higher professional training in thyroid and other endocrine diseases.

The RCP lays out a reasonable plan for the first step in their guidance: the vast majority of patients with suspected thyroid disease are supported very well in primary care by their GPs, and their condition, hypothyroidism or otherwise, is appropriately diagnosed and well managed”, but they then fail to follow this through.

Their plan is true for around 85% of those suffering symptoms, who are being treated with L-T4 monotherapy. However, what TPA is concerned about, are those 15% of the UK thyroid population who remain ill on L-T4 monotherapy, because they are suffering from deficiencies (post-thyroid), which are not being acknowledged.

The RCP further state that … some patients are inappropriately diagnosed as being hypothyroid (often outside the NHS) and are started on L-thyroxine monotherapy or other thyroid hormones, which will not only cause them possible harm, but leaves the true cause of their symptoms undiagnosed and therefore untreated.

TPA is concerned about the definition in the RCPs policy statement of hypothyroidism or otherwise. Are the or otherwise the 15% of the UK thyroid community who are not suffering because of under-activity of their thyroid gland, yet continue to suffer the same symptoms as hypothyroidism?

The RCP states: Patients with continuing symptoms after appropriate thyroxine treatment should be further investigated to diagnose and treat the cause.

They further state: We recommend that those patients whose thyroid blood tests are within the reference ranges but who have continuing symptoms, whether on levothyroxine or not, should be further investigated for non-thyroid causes of the symptoms.

However, the RCP then gives no recommendations or details as to what investigations should be undertaken, nor what tests should be done, nor do they acknowledge the possibility that such patients may be suffering from thyroid hormone deficiency in target tissues, eg Low T3 Syndrome or Euthyroid Hypometabolism.

This condition, which has been reported upon in medical literature for over half a century, is not being acknowledged in the endocrinology specialty, nor is it being discussed in conventional medical circles.

Furthermore, most medical practitioners do not seem to know what causes it, nor do they know what to do about it.

However, this condition is NOT caused by a problem with the thyroid gland. This is a crucial distinction, and it is what distinguishes Low T3 Syndrome or Euthyroid Hypometabolism from Primary Hypothyroidism. This condition cannot be treated with T4-only.

The endocrinology speciality also does not take into consideration the possibility that the cause for patients’ complaining of continuing symptoms on L-T4 monotherapy may also be due to many other things, such as:

– adrenal fatigue
– low levels of specific nutrients
– partial response to L-T4 monotherapy
– failure of the deiodinase enzymes
– receptor resistance
– food allergies
– the presence of systemic candidiasis
– other hormone imbalances

A timely and radical review is urgently needed by an increasingly knowledgeable and empowered public, as well as by those doctors who are currently struggling to provide what they know to be the most appropriate treatment for their patients.

Bearing all of these shortcomings in mind, it is the opinion of TPA that there is no validated published research showing that L-T4 monotherapy is safe and effective for ALL sufferers of hypothyroid symptoms, and therefore, the proposition by the RCP and the BTA that levothyroxine is safe and effective for ALL sufferers CANNOT and MUST NOT be relied upon.

CONCLUSIONS AND RECOMMENDATIONS

TPA are extremely concerned that the current positions of the RCP and the BTA advocating L-T4 monotherapy for ALL patients suffering symptoms of hypothyroidism, are causing real harm for at least 300,000 UK citizens.

TPA STRONGLY URGES THE RCP AND BTA TO WORK WITH TPA AND THYROID PATIENTS, IN ORDER TO BRING ABOUT AN END TO THIS STATUS QUO, WHICH TPA FEELS IS THE RESULT OF MANY FAILINGS, AS OUTLINED BELOW.

In the RCPs policy statement on the Diagnosing and Management of Primary Hypothyroidism and the BTAs statement on Armour Thyroid v L-T4 monotherapy BOTH HAVE FAILED TO TAKE INTO ACCOUNT :

1. – human rights (and the Colleges responsibility, according to its Charter) – when sufferers are put at risk through a disregard for the demand that patients should be treated with fairness, respect, equality, dignity and autonomy (FREDA). [1]

2. – the confusion caused by the RCP and BTA through the use of vague and loose expressions, such as Primary Hypothyroidism and Hypothyroidism, which mean different things. Despite this, the RCP and BTA statements use these expressions in an interchangeable way. [2]

3. – the scientific evidence cited in TPAs previous rebuttal to the RCP policy statement [3] and the BTAs Statement on Armour Thyroid v levothyroxine (T4) monotherapy (2007). [4] Such evidence demonstrates the existence of an analogous situation surrounding potentially enforced guidance for ALL those suffering symptoms of hypothyroidism, yet the RCP have written to TPA that they will not enter into further discussion. [5]

4. – the 1997 study that showed endocrinologists attempts to correlate symptoms and signs of hypothyroidism with modern thyroid blood tests. Results were published in the Journal of Clinical Endocrinology [6] – 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.” However, the RCPs and the BTAs policies have failed to take account of this.

5. – the study showing that although it is widely accepted that thyroid hormone replacement for patients with hypothyroidism can be fully accomplished with L-T4 monotherapy, as assessed by serum thyroid function tests, where approximately 10% of hypothyroid patients are dissatisfied with the outcome, and physicians continue to report benefits from combined levothyroxine-triiodothyronine therapy for some hypothyroid patients. Recently, a large prospective study reported that the benefit of the combined T4 and T3 is associated with the Thr92Ala polymorphism in the type 2 deiodinase gene, which is present in about 15% of the general population. If confirmed, these findings indicate that personalised medicine is rapidly catching up with modern thyroidology. [7]

6. – recommendations that both Thyroid Stimulating Hormone (TSH) and free T3 measurements are required in order to achieve a definitive diagnosis and develop an appropriate treatment approach. It has been suggested that in rare instances, thyroid hormone measurements, and NOT TSH measurements, are the most relevant and appropriate indicators of thyroid status. [8, 9]

7. – the Differential Diagnosis Protocol (DDX) – although the RCP policy statement is about The Diagnosis and Management of Primary Hypothyroidism, [2] some of its restrictions go beyond primary. Whilst most patients are diagnosed and treated appropriately, a growing minority are increasingly knowledgeable about, and are dissatisfied with their therapy. Doctors should consider all possible causes for those suffering residual symptoms on T4 monotherapy. [10-35] Peripheral thyroid hormone physiology exists, and must be included in the RCP Training Curriculum, [36] and the GMC Endocrine Curriculum. [37] The Differential Diagnosis Protocol [38] requires examination of ALL physical issues and potential causes for symptoms, [39-41] but endocrinology ignores them. Failure to take account of the available evidence and research may amount to medical negligence.

8. – the recommendations in their own policy statements, that patients with continuing symptoms, after appropriate thyroxine treatment, should be further investigated, to diagnose and treat the cause, [2] and yet they fail to indicate what further investigative tests should be undertaken. In the context of defining failure of the thyroid system, the recording of the Basal Temperature can be useful in providing valuable clinical backup. [42]

9. – the AGREE Instrument [43] – that provides an internationally agreed framework for assessing the quality of clinical practice guidelines. Each recommendation should be linked to the references on which it is based. Both the RCP and BTA statements fail to supply such references, leaving their recommendations without concrete underpinning. Each statement should have a clearly indicated scientific basis.

10. – other thyroid functions (apart from the thyroid gland) that take place in the peripheral tissue (the peripheral conversion of the pro-hormone T4 to the active hormone T3) – ie the thyroid hormone reception by the peripheral cells, the up-regulation of the cellular respiratory cycle, and the clearance of hormones they believe function perfectly. This assumption is contrary to the basic philosophy of allopathic medicine, ie all bodily functions may become deficient or fail. UK endocrinology does not take into account the overall view of the greater thyroid system (GTS), from the hypothalamus to the up-regulating of the cellular production of energy and the clearance of thyroid hormones. The GTS table fully illustrates the flow through this system, starting at the top of the chart – with signals from the brain to the bottom of the chart, where the symptoms are sensed. This table should be included in both the RCP Teaching Curriculum and the GMC Endocrine Curriculum. [44]

11. – the very important consequences of the RCP statements on hypothyroidism that summarily dismiss studies showing T4-only does not work for all. When a doctor puts the policy statement into practice, it renders that doctor unable to properly diagnose and treat a large minority of patients who are experiencing symptoms of hypothyroidism, because their curriculum fails to give instructions on the physiology and biochemistry of thyroid hormones, and it does not recognise the full array of manifestations of failure of the thyroid system. [2, 36] Consequently, it is TPAs view that current medical educational and training systems need to be urgently reformed, in order to enable doctors to properly diagnose and treat patients who come to them with symptoms of hypothyroidism.

12. – the issue that incorrect diagnosis and treatment of symptoms of hypothyroidism and concern arising out of it has been topical in local and online patient advocacy groups for many years. On 27 July 2014, an article appeared in the UKs Sunday Telegraph – Could a Renegade Doctor Save Your Life?. [45] This article was followed by an article published online (26 August 2014) entitled “Cold Hands? Always Tired? It Could Be The Hidden Thyroid Problem Many Doctors Refuse to Treat. [46] This debate quickly moved to the mainstream media.

13. – the huge financial burden to the NHS, and the overwhelming burden to the quality of life of hundreds of thousands of UK patients left suffering on the RCPs recommended L-T4 monotherapy, who chronically use more prescription drugs, especially for diabetes, cardiovascular disease and gastrointestinal conditions [47] – failing to take into account the considerable cost of other medicines prescribed because the L-T4 monotherapy does not fully resolve those patients suffering from thyroid hormone deficiency in target tissues, because, as TPA have indicated, doctors are not taught how the whole of the thyroid system functions, nor how such patients can benefit from thyroid hormones other than L-T4 monotherapy. TPAs research has shown that in cases of unresolved hypothyroidism, doctors often give patients a diagnosis of depression, CFS, ME or FM, amongst others, and they then prescribe medications to fit each symptom.

14. – Irving Kirschs Department of Psychologys Study (at the University of Hull) (25 February 2008), which was the first to examine both published and unpublished evidence of the effectiveness of selective serotonin reuptake inhibitors (SSRIs) – which account for 16 million NHS prescriptions a year. The largest study of its kind concluded that antidepressant drugs do not work. More than 291 million was spent on antidepressants in 2006, including nearly 120 million on SSRIs. [48] The majority of the 10,500+ subscribers to the TPA online thyroid support forum complain that their doctors prescribe these drugs, believing that their patients problems are not real – patients are told that their symptoms are all in their head.

15. – the fact that drug sales are underpinning the current approach to thyroid disease, instead of consideration being given to the health and well being of the population. [49, 50]

16. – requests by TPA, asking the RCP to improve their imprecise, and consequently misleading, language in their policy statement on primary hypothyroidism – that has contributed to false conclusions about what constitutes proper diagnosis and treatment of hypothyroid symptoms. [2, 12, 51-57] The results of these errors have led to unacceptable standards of care.

17. – the link between low thyroid hormone function and heart failure, which has been discussed for over 60 years. A growing body of evidence, particularly in recent years, suggests that thyroid hormone may improve clinical outcomes. Thyroid hormones offer the promise of improving ventricular contraction and relaxation, improving coronary blood flow and inhibiting atherosclerosis, and new results suggest they may even reduce the incidence of arrhythmias in heart diseases. There is much clinical evidence related to thyroid hormone dysfunction and heart failure. The RCP policy statement should be reviewed on a regular basis as and when such new research is forthcoming. [58]

18. – the fact that levothyroxine was introduced as The Gold Standard, without any comparison with natural thyroid extract, and the Medicines Control Agency (MCA) has continued its use without review. The burden of proof lies with the synthetic product to demonstrate it is as safe, effective and consistent as NDT. [59-61]

19. – patient counterexamples to T4-only therapy – ignoring counterexamples is not tolerated in other sciences but is encouraged by Evidence-Based Medicine (EBM). A scientist who finds a counterexample to their idea, must limit or abandon it as not reliable. [62-64] TPA has a register of 2080 patient counterexamples who continued to suffer symptoms on L-T4 monotherapy and found those symptoms were mitigated or disappeared once they started on a T3-hormone containing product. The majority of these patient counterexamples are willing to testify.

20. – further to the above, the total number of subjects in all 13 studies cited by three meta-analyses is 1398. The objective of the Register of Counterexamples is to draw to the attention of those responsible authorities the dire need for an urgent re-examination of the existing protocol for the diagnosis and management of the symptoms of hypothyroidism, and to challenge those studies previously undertaken, that concluded that T4/T3 combination worked no better than L-T4 monotherapy. There are also 72 counterexamples in previous studies by Goldberg [32] plus Basier et al. [40] Sir Karl Popper postulates that a single counterexample is sufficient. [64]

21. – the results of the TPA Hypothyroid Patients Survey (undertaken 2005-2006). In this survey of 1500 hypothyroid patients, the dissatisfaction of many patients is highlighted. The survey asked patients undergoing L-T4 monotherapy: Do you feel that you have fully regained your optimal state of health? A staggering 1176 (78.4%) answered NO [65] to this question. This result appears to be confirmed by the recently published retrospective analysis showing NDT was preferred over T4-only therapy by 78% of patients with hypothyroidism in the sub-group with persistent subjective complaints whilst on L-T4 monotherapy. [66]

22. – the results of one study screening for adult hypothyroidism that suggested 100,000 people with under-active thyroids would benefit from T4 treatment. [67] However, according to the BTA, BTF, ACB et al, [68] screening for thyroid dysfunction in a healthy adult population is not warranted.

23. – those patients whose blood tests have been restored to normal with L-T4 monotherapy yet who continue to have symptoms, showing that modern thyroid treatment using L-T4 monotherapy is often unsuccessful. Reliance on laboratory tests, without clinical evaluation, may lead to considerable diagnostic errors. [12, 69-72]

24. – the results of the work by Kirk and Kvorning (1947), who found that some patients symptoms of hypothyroidism are not mitigated by T4 alone [73] because the post-thyroid functions in the tissues produce, receive, and operate with the active hormone T3. This was confirmed by Means in 1954 [74] and again, by Baisier, Hertoghe and Eeckhaut in 2001, in their 15-year study of their patients. [12]

25. – the numerous reports of many defects in the commercial T4 preparations. [75-78]

26. – the concerns, in 2005, of many endocrinologists, with regard to the performance of levothyroxine sodium. As a result, the FDA requested product stability data from manufacturers of all approved products manufactured between July 2003 and June 2005. The FDAs letter to the manufacturers of Synthroid (Eltroxin UK) summarised all the dangers of inconsistent dosing for hypothyroid patients. In particular, they state: “.patients using Synthroid have experienced significant, unintended variations in their doses of levothyroxine sodium… these variations are not conducive to proper control of hypothyroidism. [79]

27. – the numerous conditions that may reduce the conversion of T4 to T3, eg aging, obesity, disease, stress, exercise, malnutrition etc – potentially reducing the efficacy of L-T4 monotherapy treatment, and suggesting that a natural or synthetic T4/T3 treatment is more effective. [80, 81-83, 108]

28. – further evidence of the potential benefits of a combined T4/T3 treatment protocol and the fact that thyroid hormone replacement therapy should aim to reproduce as closely as possible the natural secretions of the thyroid gland. The RCP and BTA should give more support for the use of whole thyroid extracts. To this end, the effectiveness of whole NDT versus L-T4 monotherapy should be compared in further clinical trials, especially involving problematic patients. Natural thyroid extract is a combination T4/T3 and there is evidence that combinations of synthetic T4/T3, or T3 alone treatments, result in greater improvement of clinical symptoms than L-T4 monotherapy, which therefore supports the argument in favour of treating with a combination of T4/T3. [82-94]

29. – the fact that adding T3 to T4 results in greater improvement of clinical symptoms and signs in those patients suffering symptoms of hypothyroidism, [95] eg when T3 and T4 are both added to food simultaneously with goitrogens, a better prevention of goitre is obtained than when L-T4 monotherapy is added, even at 7 times higher concentration. [96] In humans, T4/T3 treatments have been shown to reduce serum cholesterol and increase the speed of the Achilles Tendon reflexes better than L-T4 monotherapy. [97] Several studies in rats rendered hypothyroid show that cellular euthyroidism is only obtained in the target organs if L-T3 is added to the classic L-T4 medication. [80, 98, 99]

30. – the fact that T3 is thought to be between four and five times as potent as T4. [100, 101] The absorption of oral T4 can be variable (50% to 73%), contrasting with that of T3, which is more constant and efficient (95%). [80, 102]

31.- the fact that there are toxic substances such as phenols, cadmium and mercury, and medications such as propranolol, amiodarone and several others, that may interfere with or inhibit the conversion from T4 to T3, [109-115] and that deficiencies in hormones, such as T3 itself, TSH, growth hormone, insulin, cortisone and deficiencies in certain trace elements, such as selenium, iron, zinc, copper and iodine, that partially block this essential conversion step for thyroid function. [18, 116-125] On the other hand, excess hormones such as glucocorticoids, ACTH, oestrogens and some trace elements may slow down the conversion of T4 to T3. [126, 127]

32. – those people who need T3-containing therapies for their post-thyroid deficiencies, who have great difficulty getting them prescribed. This is because many UK medical bodies are not considering all the available evidence. Such disregard of evidence is clearly demonstrated in the BTAs referenced meta-analysis by Grozinsky-Glasberg et al (2006), advocating the supremacy of L-T4 monotherapy over combination therapies, that summarily dismissed 98% of the available relevant studies, by rejecting 490 papers out of 501 – including ones that produced counterexamples to blanket prescriptions of all forms of T3 therapies. [128] The RCP claim the only evidence in the related medical science is contained in 11 randomised clinical trials that compare L-T4 monotherapy with combination T4/T3, a claim which TPA would dispute. This leads to assertions by medical bodies that evidence is not available, whereas it does appear to be.

33. – the available science showing many patients benefit from being treated with T3 – for those suffering from thyroid hormone deficiency in target tissues, irrespective of its cause, and all those randomised clinical studies that show such treatments result in greater improvement of clinical symptoms than L-T4 monotherapy, which therefore supports the argument in favour of treating with combination therapy in appropriate cases. [10, 51, 83-85, 88, 89, 94, 96, 129-133]

34. – the fact that all alternative treatments to synthetic T4 and T3 are supported by decades of research and practice, showing that patients with continuing symptoms of hypothyroidism on L-T4 monotherapy SHOULD NOT BE DENIED synthetic T3 and/or NDT. It is only possible to use L-T4 monotherapy if there is no thyroid hormone deficiency in target tissues and the peripheral conversion has sufficient extra capacity to handle the extra T4 needed to replace the thyroids production of T3. [82,129]

35.- the fact that both animal-derived and synthetic hormones are equally unstable compared to many other drugs. Thyroid hormones consist of iodine atoms bound to the amino acid tyrosine. The iodine atoms easily separate from the tyrosine. [93] It is therefore prudent for doctors and patients to be vigilant for sub-potent tablets or capsules.

36. – the long history and successful use of thyroid extract in America, where NDT products successfully compete with the heavily promoted synthetic T4 and T3 preparations. Not only are whole glandular extracts often superior to L-T4 monotherapy for the treatment of hypothyroidism, but there is evidence to suggest that such products are superior to combined synthetic T4/T3 preparations also. [82,134]

37. – evidence showing the variation of thyroid hormone in Armour Thyroid is minimal and well controlled (maximum 5-10%), as specified by the US FDA. There are many thyroid extract preparations and the trademark Armour Thyroid should not be used as a generic name for these. [16, 59-61] The RCP and BTA ignore the fact that T3 in natural thyroid extract is absorbed more slowly than synthetic (purified, unbound) T3. [96] The manufacturers of Armour Thyroid (Forest Pharmaceuticals) have not carried out any studies into the specific amounts of T2, T1, calcitonin or any other T hormones that are naturally occurring in desiccated thyroid, and nothing has been removed during processing. [135]

38. – evidence presented in the Empirical use of Armour Thyroid by Gaby, that many people have hypothyroidism symptoms undetected by laboratory thyroid-function tests. Cases are reported to support the empirical use of ArmourThyroid. Clinical evaluation can identify individuals with sub-clinical hypothyroidism, that are likely to benefit from thyroid-replacement therapy. In a significant proportion of cases (around 15%), treatment with thyroid hormone has resulted in marked improvement in chronic symptoms that had failed to respond to a wide array of conventional and alternative treatments. In some cases, treatment with NDT has produced better clinical results than L-T4 monotherapy. Research supporting the existence of sub-clinical hypothyroidism is reviewed, and the author’s clinical approach to the diagnosis and treatment of this condition is described. [134]

39. – research into why combination therapy may be more effective for some people. Only combined therapy with constant delivery of both L-T4 and L-T3 fully normalized T3-dependent metabolic markers and gene expression in Tx rats. These findings have important implications that may support the role of combination therapy in the treatment strategy for humans with hypothyroidism and thus may drive the need for development of improved pharmacologic modes for L-T3 administration and for high-quality randomized controlled trials in humans“. [136]

40. – the fact that the normal thyroid gland contains approximately 200mcg of T4 per gram of gland, and approximately 15mcg of T3 per gram of gland. The ratio of these two hormones in the circulation does not represent the ratio in the thyroid gland, since about 80% of peripheral T3 comes from monodeiodination of T4. Peripheral monodeiodination of T4 also results in the formation of reverse T3, which is iatrogenically inactive. [80] A similar ratio can be obtained by prescribing both NDT and L-T4, although clinical response and symptom control should take precedence over a theoretical ideal. Perhaps the ultimate form of thyroid replacement for difficult patients is whole thyroid extracted from animals, such as Armour Thyroid tablets. [137-139]

41. – the report about a patient who was treated unsuccessfully with a combination of synthetic T4 and T3, who experienced a dramatic improvement when switched to Armour Thyroid. [139]

42. – the report by Arem about the considerable difficulties he experienced switching patients from NDT to the new L-T4 and L-T3 preparations, when they first became available. According to Arem: “The new treatment was seldom entirely successful.” Arem continues: “Once switched from these natural T4/T3 tablets to T4 tablets, patients complained of sluggishness, decreased memory, impaired concentration, and a host of symptoms of ill-being. This was in spite of having reached normal blood levels of thyroid hormone and TSH”. [140]

43. – the millions of patients who have used, and continue to use, NDT safely and effectively, and have done so for over a century. Before the advent of the TSH test in the early 1970s, patients used these products in much higher dosages than they do today. [141] To date, the RCP and BTA have been unable to produce evidence to show that patients were harmed by these higher dosages.

44. – at least a third of treated hypothyroid patients whose blood tests have been restored to normal continue to have symptoms, showing modern thyroid treatment is often unsuccessful – a fact which is hardly surprising given that T3 is the crucially important active thyroid hormone – the commonly seen failure to convert T4 to T3 will result in an unsatisfactory treatment outcome. [139, 140, 142, 143]

45. – the fact that patients who remained polysymptomatic on T4-only treatment, who were switched to natural thyroid extract, became biochemically euthyroid and completely symptom-free. [142,143]

46. – the 1980 study that showed a number of manufacturers, other than Forest Pharmaceuticals, who had generic versions of desiccated thyroid that were found to be unreliable in potency. However, the amounts of T4 and T3 in Armour Thyroid USP were found to be constant. Moreover, two-year old tablets and fresh tablets of Armour Thyroid contained similar amounts of T4 and T3, [69] but, during testing of several batches of Armour manufactured between March and August 2005, it was found that some of the samples were not maintaining full potency. To avoid potential problems, it was decided to recall all the Armour tablets made during that timeframe in 2005. A Forest Pharmaceuticals spokesperson stated that very little of the recalled product had remained in circulation at that time. [75] Interestingly though, other evidence has shown that the variation of thyroxine in L-T4 can be greater than 30% in some batches. [79]

47. – the fact that there are advantages to using natural desiccated thyroid extract that are not related to its T3 content. Broda Barnes observed that some patients treated with an L-T4/L-T3 combination continued to experience residual symptoms, particularly dry skin and oedema. Both symptoms were resolved within 1-2 months when the treatment was changed to Armour Thyroid. [14]

48. – the very recent controlled trial on Armour Thyroid v L-T4 monotherapy – the results of which were published in the May 2013 Journal of Endocrinology by endocrinologists at the Walter Reed National Military Medical Center in Bethesda, Maryland, [64] and the recently published retrospective analysis showing NDT was preferred over L-T4 monotherapy by 78% of patients with hypothyroidism in the sub-group with persistent subjective complaints whilst on L-T4 monotherapy. [145] The RCP and BTA have also failed to take into account those studies using Armour Thyroid per se in 3 of 12 studies, [146-148] and 9 further studies reporting direct comparison of the two forms of treatment, ie natural v synthetic thyroxine only. [12, 149-156] They also failed to take into account studies that established the clinical benefits of NDT. [157-176] and studies showing the therapeutic equivalence of NDT, L-T4 and L-T3. [148, 177, 178]

49 – the study published in 1972 in which researchers wrote: The present study was designed to compare the effects of desiccated thyroid and mono-sodium l-thyroxine [T4] administered by mouth, on serum lipids in a group of hypothyroid patients. The researchers reported that a cholesterol-lowering effect was manifested by the time of first testing after institution of desiccated thyroid or l-thyroxine treatment. The researchers wrote further: The magnitude of the hypolipidemic (fat lowering) effects, were similar when desiccated thyroid and l-thyroxine were given orally in therapeutic equivalent doses. [147]

50. – another direct comparison published in 1978, where the researchers wrote: The biologic effect of the two therapies was compared by estimating by interpolation the dose of thyroid hormone that caused the peak serum TSH after TRH to fall to 5 U/ml. They concluded: a daily dose of 100 mcg of T4 was on average equal in biologic activity to 100 mg of desiccated thyroid; 60 mg of desiccated thyroid was equal to 60 mcg of T4. [148, p1518]

51. – the fact that the Medicines and Health Care Regulatory Agency (MHRA) does allow doctors to prescribe the brands Armour Thyroid, Erfa Thyroid, WP Thyroid and Nature Throid [177] to those patients who continue to suffer on L-T4 monotherapy, even though these products remain unlicensed in the UK. Armour is a fully official FDA-registered drug in the USA. It is legal to prescribe Armour Thyroid and the other branded NDTs to a patient in the UK and it can be delivered by UK pharmacies if there is a prescription from a licensed physician. Indeed, branded NDTs can be obtained very simply on a named patient basis and Idis World Medicines or Pharmarama will source them. [180]

52. – the fact that Armour and several other thyroid medications remain unlicensed in the UK is because they were ‘grandfathered’ in when Congress passed the ‘Kefauver-Harris Drug Efficacy Amendments of 1962’ to tighten control over drugs. Before marketing a drug, manufacturers had to prove the safety and effectiveness for the product’s intended use. The requirement was applied retrospectively to 1938, when the Food, Drugs and Cosmetics (FDC) Act was passed. Pre-1938 drugs were allowed, because they were generally recognised as safe and effective, provided no evidence to the contrary developed. Too much evidence to the contrary developed concerning the levothyroxine products and the FDA decided none were generally recognised as safe and effective, so those synthetic products lost their ‘grandfathered’ privilege and had to go through the NDA process.

Armour Thyroid continues to retain its ‘grandfathered’ status, since no evidence to the contrary has developed concerning its safe and effective status. [181,182]

TPA takes the view that ALL doctors should have freedom of choice in prescribing L-T4 monotherapy, combined L-T4/L-T3, L-T3 monotherapy or natural desiccated thyroid extract, depending upon the particular thyroid or thyroid related condition their patient is suffering. The selection of treatment, whether synthetic or natural, should be a matter between the patient and the doctor.

Medical practitioners should abandon the misconceptions that thyroid extract and/or L-T3 is inconsistent, dangerous, unreliable and/or outdated, and recognise that Armour Thyroid, Nature Throid, WP Thyroid and Erfa Thyroid all meet the stringent guidelines laid down by the United States Pharmacopoeia (USP) and the FDA, and that NDT products have been used safely and effectively for over a century.

In addition, medical practitioners should be strongly encouraged to make a full assessment of the clinical presentation of patients already using L-T4/L-T3 combination or NDT.

TO QUOTE ONE PATIENT:

….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.

TPA once again calls upon the Royal College of Physicians and the British Thyroid Association to engage with Thyroid Patient Advocacy, to further discuss the evidence presented in this paper and to initiate a review of the guidance issued to clinicians for ALL patients suffering with continuing symptoms of hypothyroidism when undergoing L-T4 monotherapy.

References: List of references  

Tags:

You must be logged in to post a comment.

Previous comments