TPA Rebuttal to incorrect statements made by local CCG’s on funding NDT and synthetic T3
INTRODUCTION TPA Rebuttal to Statements made by a local Clinical Commissioning Groups (CCG) on their refusal to fund natural thyroid extract – or synthetic T3.
The problem with the dissatisfaction of patients, who have been diagnosed with hypothyroidism and treated with the one-and-only mainstream therapy of the pro-hormone Levothyroxine [L-T4], is that this treatment does NOT work for ALL patients suffering symptoms of hypothyroidism. It can work OK for approx. 85% of patients who have been diagnosed with hypothyroidism (properlydefined as a deficiency in secretion of hormone by the thyroid GLAND), but for the 15% who suffer the same symptoms and signs of hypothyroidism, L-T4 doesnt work because they are suffering with a non-thyroidal condition that may need to be treated with a different medication or hormone. When these 15% of patients complain of continuing symptoms when treated with L-T4 monotherapy, many are given an incorrect diagnosis of ME, CFS, FM, depression, functional somatoform disorder – or even old age and sent on their way without further investigation or treatment.
More knowledgeable doctors have given patients who remain ill on L-T4 monotherapy, a trial of natural desiccated porcine thyroid extract (NDT) and found they regained their optimal health. NDT has been around for 120 years and used safely and effectively since that time. NDT was the ONLY thyroid hormone replacement for those suffering symptoms of hypothyroidism for over 50 years before the manufacture of synthetic L-T4 and never presented a problem.
The prescription of NDT for these patients had, in a lot of cases, been funded previously by local Primary Care Trusts (PCT), but when the PCTs were abolished on 31 March 2013 as part of the Health and Social Care Act 2012, their work was taken over by local Clinical Commissioning Groups. (CCGs)
Since that time, many CCGs are refusing to fund NDT and advising doctors they should not prescribe it for their patients within their area. Doctors are left with no choice but to prescribe their patient the synthetic pro-hormone L-T4 again, which did not previously work for them, which was the reason they were given a trial of NDT in the first place. Even though CCGs have no knowledge of the patients past medical history, they refuse to reconsider their decision. Such advice by a CCG to the doctors in their area is taking away a doctors autonomy in choosing a medication s/he considers best practice for their patient. The decision made by CCGs to remove funding of NDT for those who need it will mean the number of patients already being harmed by L-T4 monotherapy will rapidly increase.
CLINICAL COMMISSIONING GROUPS LEGISLATION
CCGs have legal duties to promote the involvement of patients and their carers in decisions made about healthcare services under section 14U of the NHS Act 2006. They also have a legal duty to act with a view to enabling patients to make choices with respect to aspects of healthcare services provided to them under section 14V of the NHS Act. However, CCGs also have precise legal procurement obligations under the snappily titled National Health Service (Procurement, Patient Choice and Competition) (No.2) Regulations 2013,  which require CCGs to take decisions concerning the placing of healthcare contracts in accordance with a specific set of factors guiding the decision
The views of patients on how and where they wish to have healthcare services provided to them form no part of the decision making process under the 2013 regulations. So if CCGs take patients wishes into account as a major factor in decision making they will comply with their duties under sections 14U and 14V, but will potentially act outside the framework for decision making under the 2013 regulations.
Alternatively if a CCG sticks strictly to the framework of decision making under the 2013 regulations it will have to place little weight on patients choice and the involvement of patients in decisions about their own healthcare. This makes for an impossible situation as it involves a clash between NHS services as a public service tailored towards individual needs and designed for an individual (the personalised healthcare agenda, and NHS services as contract that must be placed in the open market in a way that is fair to all potential suppliers of the services (the NHS as a market agenda)
The CCG in question therefore is removing not only Valid Consent via this unilateral demand, but are also advocating changing medical therapy analysis without seeing or talking to the patient.
According to the General Medical Councils (GMC) Prescribing guidance: Remote prescribing via telephone, video-link or online they state – Before you prescribe for a patient via telephone, video-link or online, you must satisfy yourself that you can make an adequate assessment, establish a dialogue and obtain the patients consent in accordance with the guidance at paragraphs 2029.
This local CCG has made a decision not to continue to fund the prescription of NDT for this patient, without first making an adequate assessment nor have they established a dialogue with the patient, in accordance with the above GMC guidelines and appear to be intent on causing this patient harm.
Below is TPAs rebuttal to the statements made in a response from one NHS local Clinical Commissioning Group (CCG) to a patient in their area who had written requesting them to reconsider their decision not to fund the prescription of NDT anymore.
CCG: Quoted directly from CCG letter to Patient.
TPA: Response from Thyroid Patient Advocacy to each CCG statement made.
CCG: Dear ****
Thank you for your email enquiring about the prescribing of Natural Desiccated Thyroid (NDT) extract also known as Armour Thyroid which was forwarded to me.
TPA: Armour Thyroid is the name of only one of the 4 different brands of natural desiccated porcine thyroid extract, the others being WP Thyroid, Westhroid and the Canadian Erfa Thyroid
CCG: As Im sure you are aware, NDT is derived from porcine thyroid gland and contains a combination of levothyroxine (T4) and liothyronine (T3), used to treat hypothyroidism.
TPA: The ratio of Armour Thyroid T4 to T3 is 4.22:1 (4.22 parts of T4 to one part of T3). The manufacturers state that the amount of thyroid hormone present in the thyroid gland may vary from animal to animal. To ensure that Armour Thyroid tablets are consistently potent from tablet to tablet and lot-to-lot, analytical tests are performed on the thyroid powder and on the actual tablets to measure actual T4 and T3 activity. The response by Richheimer and Jensen, should serve to correct any misrepresentations (implied or otherwise) regarding the liothyronine and levothyroxine content in Armour and the nature of the collaborative study for the U.S. Pharmacopeia (USP). As determined by Armour Pharmaceutical Company and other participating laboratories, the liothyronine and levothyroxine content in Armour is well within the specifications set by the U.S. Pharmacopeia.
CCG: It is unlicensed in the UK:
TPA: Armour remains unlicensed in the UK because it has never required a licence. In the United States, Armour Thyroid and several other thyroid medications were ‘grandfathered’ in when the US Congress passed the Kefauver-Harris Drug Efficacy Amendments of 1962, to tighten control over drugs. Before marketing a drug, firms had to prove safety and effectiveness for the products intended use and also provide substantial evidence of effectiveness for the product’s intended use. That evidence had to consist of adequate and well-controlled studies, a revolutionary requirement. The requirement was applied retroactively to 1938, when the Federal Food, Drug, and Cosmetic Act was passed. [6,7] Pre-1938 they were allowed because they were generally recognised as safe and effective, provided no evidence to the contrary developed. The NDT brands Armour Thyroid, WP Thyroid, Nature Throid and Erfa Thyroid, retain their grandfathered’ status since no evidence to the contrary has developed concerning their safe and effective status.
CCG: The prescribing of products that do not have a UK product license is not supported locally, even though they may have a license in another country.
TPA: The Medicines and Healthcare Products Regulatory Agency (MHRA) do allow NDT to be prescribed because of its grandfathered status. [6,7] Synthetic T3 and synthetic combination of T3 and T4 have been approved and indicated. The MHRA have information on their website regarding Medicines that do not need a licence  and they have also produced letters giving information about the prescription of the branded NDTs within the NHS.  The GMC have also set out their prescribing guidance of unlicensed medicines 
The products in question do not require a licence. They are standardised to the specifications laid down by the USP. Full clinical information for prescribers is readily available on the individual manufacturers official website. [11-15] All such evidence has been forwarded, by TPA, to the Presidents of the RCP, the BTA, and the NHS UK Medicines and the NHS UKMi) .
CCG: Some unlicensed products have been reviewed by the ******** Area Prescribing Committee (APC) but have been considered not suitable for prescribing in *******. 1 There is also no standardisation of quality, efficacy or safety.
TPA: There may be some unlicensed products that this CCGs Area Prescribing Committee consider not suitable for prescribing, but this does NOT apply to the branded NDTs which are standardised to the specifications laid down by the USP (see above).
Interestingly, in a 1980 study, a number of generic versions of desiccated thyroid were found to be unreliable in potency. Do we, then, assume that the Area Prescribing Committee in question has checked only the generic versions of NDT and NOT the branded NDTS? The Medicines and Healthcare Regulatory Agency (MHRA) state categorically that all of the above (unlicensed) brands can be prescribed by doctors on a named patient basis, where their patient has not regained their optimal health using the licensed mainstream product (L-T4). The MHRA has not objected to the importation of these products provided that they are authorised prescription only medicines, standardised to the USP, and that they are for the treatment of patients with thyroid diseases, for whom the UK licensed synthetic thyroid hormones are not suitable. [6,7] The MHRA would not make such a recommendation if these branded NDTs had not been found to be of good quality, safe and effective , nor would they allow its prescription if it was considered harmful.
CCG: Whilst doctors are not totally prohibited from prescribing unlicensed medicines, the General Medical Council (GMC) guidance on prescribing unlicensed medicines states that when prescribing an unlicensed medicine prescribers must be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy. 2
TPA:The GMC also state  that doctors may prescribe unlicensed medicines where, on the basis of an assessment of the individual patient, you conclude, for medical reasons, that it is necessary to do so to meet the specific needs of the patient where :
- There is no suitably licensed medicine that will meet the patients need. Examples include (but are not limited to), for example, where (i) there is no licensed medicine applicable to the particular patient – or (iv) the patient needs a medicine in a formulation that is not specified in an applicable licence.
- Or where a suitably licensed medicine that would meet the patients need is not available
- The GMC Footnote on the above website also states This definition is based on information published by the Medicines and Healthcare Products Regulatory Authority (MHRA) which is the licensing and regulatory body for the supply and use of medicines and medical devices. MHRA guidance on the lawful supply and use of unlicensed medicines is set out in the MHRA publication the supply of unlicensed medicinal products (specials), MHRA Guidance Note 14 
The MHRA Review of Unlicensed Medicines makes the point that: Clinicians should have the ability in appropriate circumstances to exercise their professional judgment to commission the supply of an unlicensed medicine to meet the special needs of an individual patient but the RCP Policy Statement takes away a their autonomy meaning that doctors can no longer use their professional judgment.
There IS substantial evidence supporting the use of combination therapy, but conventional medical practitioners have made no attempt to evaluate the evidence regarding the use of NDT and their wholesale dismissal of the concept represents, at least in part, a biased attitude. This biased attitude has been produced by the extensive evidence exclusion philosophy of Evidence-Based Medicine (EBM). EBM promotes meta-analyses of randomized clinical trials as the most truthful, and hence the highest form of evidence. Consequently, lower forms of evidence, including counterexamples,are routinely dismissed: If the study wasnt randomized, wed suggest that you stop reading it and go on to the next article. This claim really means that there is no evidence that they are willing to accept. “No evidence” has been institutionalised in EBM. The problem with “no evidence” is simply that it violates the legal rules on evidence that allow applicable evidence.[20,21]
TPA executed a voluntary survey of those suffering symptoms of hypothyroidism to find patient counterexamples to endocrinology’s proscription against all triiodothyronine (T3) containing therapies. This survey was suggested by earlier studies and the evidentiary supremacy of counterexamples.  In 1960, Goldberg demonstrated euthyroid hypometabolism via diagnostics and synthetic T3 therapy. He produced 32 patient counterexamples.  In 2001, Baisier, Hertoghe and Eeckhaut disclosed a long term study and its follow up of treating 40 patients with natural desiccated thyroid (NDT). 
The TPA Register of Counterexamples Survey found over 2000 patient counterexamples to L-T4 monotherapy. This number is greater than all of the subjects in all of the meta-analysed studies, which is less than 1400. The implication of this substantial number of direct contradictions to endocrinology’s proscription is simple: The studies that support the proscription are of the special case of thyroid gland deficiency and without post-thyroid functional deficiencies in the “tissue,” where T3 is the operative hormone. Indeed, an inspection of the meta-analyses shows that the study designs were effectively limited to the thyroid gland by summary dismissal of the 98% of applicable medical science, subject choice, analysis methods, and errant conclusions.  Thus, the proscription against all forms of T3 is certainly not valid for post-thyroid deficiencies in the “tissue.”
The creation of a different survey of 1500 people suffering hypothyroid symptoms was undertaken by TPA in 2005-6 where the dissatisfaction of many patients is highlighted. When asked of those participants undergoing L-T4 monotherapy, Do you feel that you have fully regained your optimal state of health? 1176 (78.4%) answered NO.
Interestingly, this dissatisfaction by 78.4% on L-T4 monotherapy was born out in a 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,  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.  The United Kingdom Medicines Information (UKMI) Q and A on Armour Thyroid-v-L-T4 monotherapy (UKMi)  continue to ignore the substantial evidence [30-36] showing T4-alone does not work for ALL those suffering symptoms of hypothyroidism, and doctors have also reported patient dissatisfaction with T4-only therapy.[37-39]. Kirk and Kvorning (1947) and Means (1954)  also found that not all patients symptoms were mitigated with T4-only.
The RCP, BTA and UKMi also ignore the existence of numerous subsequent studies on the characteristics of peripheral conversion or metabolism of T4 to T3 and peripheral cellular hormone reception functions [42-116] These patients are NOT suffering with hypothyroidism (defined as a deficiency in secretion of hormone by the thyroid GLAND) they are suffering with a non-thyroid condition that needs a different diagnosis and therapy protocol. [39,117-119]
CCG: A statement made by the Royal College of Physicians on The diagnosis and management of primary hypothyroidism states: 3 Overwhelming evidence supports the use of thyroxine (T4 or tetra-iodothyronine) alone in the treatment of hypothyroidism, with this usually being prescribed as levothyroxine.
TPA: TPAhas asked the President of the RCP on numerous occasions to cite references to research/studies showing overwhelming evidence supports the use of thyroxine (T4 alone), but to date, they have provided none. A Freedom of Information (FOI) requested that the RCP provide such evidence – again, they provided none. A request was made via the Ask for Evidence website, run in association with Sense About Science asking for evidence on the safety and efficacy of L-T4 as a treatment for hypothyroidism. This request was directed to the RCP who eventually responded stating The RCPs guidance is based on the opinion of an expert panel which was temporarily formed for this purpose. The evidence they used to form their individual opinions has not been collated and therefore the RCP cannot provide any evidence list
While NDT can treat hypothyroidism, it also treats tissue deficiencies that are functionally post-thyroid. L-T4 monotherapy can only do this if the peripheral conversion of T4 to T3 was adequate, but the patient history of continuing symptoms on L-T4 monotherapy demonstrates this is not the case.T3 is consistent with the post-thyroid functions in the peripheral tissue, as that is what produces T3 and that is what uses T3 to up regulate the cellular respiratory cycle. There is no information about this in the RCP Teaching Curriculum on hypothyroidism. 
CCG: We do not recommend the prescribing of additional tri-iodothyronine (T3) in any presently available formulation, including Armour Thyroid, as it is inconsistent with normal physiology, has not been unequivocally proven to be of any benefit to patients, and may be harmful.
TPA: This is either erroneous or a deliberate attempt to mislead UK medical practitioners and patients. The CCG has provided no evidence to back up this statement. There is no evidence because evidence-based medicine allows the summary dismissal of evidence that is not generated by randomised clinical trials. However, there are vast amounts of evidence, much of which is given here, for those who are willing to read it.
Armour Thyroid does have a higher amount of T3 compared to T4 than the relative amounts of T3 to T4 secreted by the normal human thyroid gland, but it is well documented that Armour is often more effective and is better tolerated than synthetic preparations of T4, T3 and T4/T3 combination. Thisis because the T3 in NDT is absorbed more slowly than synthetic (purified, unbound) T3. 
CCG: There are potential risks from T3 therapy, using current preparations, on bone (eg osteoporosis)
TPA: Bone de-calcification has been associated with hyperthyroidism and associated excessive T3 levels. However, excessive serum T3 levels are an indirect measure of intracellular behaviour..there are still more factors to consider, such as peripheral cellular hormone reception and the chemistry required for intracellular operation. A study found cellular receptor defects could produce bone loss even when the subject/patient has normal hormone levels.
The adverse effects of hyperthyroidism on the skeleton were known before the advent of satisfactory treatment for hyperthyroidism. One of the first reports of hyperthyroid bone disease was in 1891 when von Recklinghausen described the “worm eaten” appearance of the long bones of a young woman who died from hyperthyroidism. With the introduction of antithyroid drugs and radioiodine in the 1940s, clinically apparent hyperthyroid bone disease became less common.
There are potential risks on bone loss if high doses of thyroid hormone is given long term. And the Journal of Clinical Endocrinology and Metabolism has said that, although controversies exist on the possible adverse effect of T4 on bone mass, most studies reported bone loss in estrogen-deprived postmenopausal women taking suppressive doses of levothyroxine. Levothyroxine- suppressive therapy was associated with bone loss in postmenopausal women; however, it could be prevented by either calcium supplementation or intranasal calcitonin. 
While the research is contradictory and sometimes confusing, the predominance of the evidence is pointing toward the conclusion that non-suppressive thyroid replacement does NOT dramatically increase the risk of osteoporosis, and that a key risk factor seems to be age and menopausal status. It does not seem logical for doctors to refuse to treat to lower-normal TSH level, or to provide supplemental and not excessive T3 treatment – both therapies which may help resolve major hypothyroidism symptoms for some patients- solely on the basis of concerns over osteoporosis. This is particularly true for patients who are pre-menopausal.
CCG: There are potential risks of T3 therapy using current preparations on the heart (eg arrhythmia).
TPA: A long-term study of 1,569 patients treated properly with establishment-dismissed desiccated thyroid showed a significantly lower rate of heart attacks than found in the five thousand subjects Framingham study 
There are other numerous studies showing the effect of low T3 and the heart and it is of great concern that this particular local CCG appears not to be even aware of these:
- Associations between thyroid hormone levels and the heart Health -Thyroid hormone levels are positively correlated with the heart rhythm.[ 126]
- A Lower Serum T3 (And Higher Serum T4) Is found in heart patients with arrhythmia.[127-132]
- Low Serum T3 and T4 levels are found in patients with coronary heart disease.
- 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).
- Progressively Lower Serum T3 levels are found in patients with Ischemic Heart Disease from Coronary Stenosis to Myocardial Infarct.[135-137]
- Low Serum Free and Total T3 (and low T4 and high TSH) levels are found in patients suffering from acute myocardial infarct with poor outcome.
- Auto-Immune Thyroidits is associated with poorer heart indices.
- Increased incidence of auto-immune thyroiditis and overt hypothyroidism in men with acute myocardial infarct, which may have contributed to the development of the disease.
- A Low Serum T3 or T4 (Hypothyroidism) is found in Cardiac Failure.[141-145]
- A Low Serum Free T3 Index/Reverse T3 ratio in chronic heart failure patients is a highly significant predictor of poor outcome.[146-148]
- A Low Serum T3 or T4 in heart patients is associated with an increased risk of cardiac arrest/death.[149,150]
- Cardiovascular disease and mortality is increased in hypothyroidism (+ 70 % for both.
- Thyroid Therapy of Cardiac Patients. 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.
- Thyroid therapy corrects the bradycardia of Hypothyroidism.
- Thyroid therapy corrects the ventricular arrhythmia.
- Coronary heart disease in Humans: Improvement with thyroid treatment.[155-158]
- Adequate thyroxine replacement in hypothyroidism prevents coronary artery disease progression.
- Desiccated thyroid therapy improves cardiac failure refractory to Digitalis in humans.[160,161]
- T3-Therapy improves the outcome of open heart surgery, especially heart transplants.
- Thyroid hormone therapy greatly reduces the lesions of experimental myocardial infarct in rats.
- Thyroid therapy reduces coronary artery disease and cardiac fibrosis in mice.
- Thyroid therapy reduced the lesions of experimental cardiac arrest in dogs.
- Thyroid therapy reduced the complications of hemorrhagic shock in dogs.
One of my recurring objects of thought has been the slowness with which raw knowledge is assimilated. For example, I have been thinking about Broda Barness work on the prevention of heart disease with thyroid extract. He did solve much of the riddle of heart attacks, but recent statements by the Heart Association show that the dominant forces in the health business havent learned anything at all from his work, which he began 50 years ago. His work is clearly presented, not hard to understand, and it is scientifically so sound that no one challenges it, at least not on the scientific level. It is ignored, rejected by people who choose not to be bothered to read it. How many people have died from heart disease, since his work first became available? (And how many more from cancer, tuberculosis, and other diseases he showed occur mainly among hypothyroid people?)
– Raymond F. Peat 
CCG: We note that the extract marketed as Armour Thyroid contains an excessive amount of T3 in relation to T4. Over-treatment with T4, when given alone, has similar risks.
TPA: See [Ref: 5]
CCG: Additionally the British Thyroid Association (BTA) issued a statement in 2007 regarding the use of armour thyroid in thyroid replacement. 4 This stated: There is no evidence to favour the prescription of Armour Thyroid in the treatment of hypothyroidism over the prescription of thyroxine sodium, as supplied in the United Kingdom.
TPA: There is NO evidence to favour the prescription of thyroxine sodium over the prescription of NDT either! What the BTA (and CCG) may not have taken into consideration is that there may be advantages to using NDT that are not related to its T3 content. Broda Barnes observed some patients treated with synthetic T4/T3 combination continued to experience residual symptoms, particularly dry skin and oedema. Both symptoms resolved in 1-2 months when the treatment was changed to NDT.This observation suggests a third active substance is secreted by the thyroid gland. The most likely candidate is diiodotyrosine (T2). Some studies have been carried out showing that T2 is very active in its hormonal activity. [169-172]
Whole thyroid extracts contain not only T4 and T3, but also T2 and T1, which also have hormonal activity.[173-185] Notably, as we have seen, T2 is very active in its metabolic effects.
CCG: There has never been a direct comparison of these two treatments. The BTA committee cannot recommend a treatment with possible side-effects, when a safe and equally well-established treatment exists.
TPA: The CCG statement is a FACTUAL ERROR. There have been direct comparisons of these two treatments. All hormones have possible side effects if treated wrongly, and the side effects and contra-indications of treating with L-T4 monotherapy are listed in the manufacturers website(s). There is much evidence to demonstrate the safety and efficacy of NDT. The CCG statement is FALSE and appears to be a deliberate attempt to mislead both doctors and patients.
TPA, in 2008, sent to the BTA a rebuttal, regarding their Statement on Armour Thyroid-v-L-T4 monotherapy giving evidence that favours the prescription of NDT over L-T4 monotherapy for some patients. TPA asked the BTA Executive Committee, at that time, to amend their misleading statements accordingly. The BTA statement has not yet been amended. 
In 2009, the late Dr John Lowe also wrote a rebuttal to the BTA Statement on Armour Thyroid-v-T4 monotherapy -stating: At the top of its homepage, the BTA once indicated that it is Encouraging the Highest Standards [sic] of Research and Patient Care. I trust that the BTAs integrity is such that it will conduct itself in accord with this statement. Hence, I also expect that its Executive Committee will revise its document on desiccated thyroid based on a careful reading of the original reports of the studies to which they refer, taking note of the findings I have described. Almost 6 years later, The BTA has taken no note of the findings Dr Lowe described, nor have they revised any part of their Statement.
NOTE: The Lowe Critique , plus E.K. Pritchards Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism,  between the two of them, probably have much of the evidence required to bring a case against the CCGs refusal to fund the prescription of NDT.
In Lowes Critique, he dissects relevant parts of the only two papers cited by the BTA Committee and points out that both papers contain errors that misinform readers who take the authors statements at face value. There is much evidence readily available that demonstrates the safety and efficacy of NDT and the medical literature contains numerous studies in which researchers compared the effectiveness and safety of different thyroid hormone therapies if only the BTA, RCP and CCG would look. Among the therapies compared in the studies were L-T4 alone, desiccated thyroid, and combined synthetic T4 /T3. Instead of referencing all of these studies, the BTA, in their Statement, cited only TWO papers in which authors reviewed the most recent studies that compared L-T4 monotherapy to synthetic T4/T3 and these are the two papers quoted by the CCG. One of those papers is a review of the studies by Escobar-Morreale et al.,  another is a report of a meta-analysis by Grozinsky-Glasberg et al,[ 188] and a literature review by Joffe et al. The problem with the latter meta-analysis is simple – IT IS NOT CORRECT! For example, the three meta-analyses that concluded T3 should continue to be proscribed have no scientific basis when applied to peripheral conversion, peripheral cellular hormone reception, and mitochondrial activity.
Lowe states: Members of the Executive Committee appear to be among the misinformed. I include citations below (sic) that indicate that the Committee accepted without question and reiterated false statements of the authors of the two papers. Possibly as a result of this, but apparently for other reasons, the Committees document contains falsehoods that I cite below.(sic) As will be obvious to readers, only if the falsehoods were true could the Committee validly deduce its conclusions about T4 replacement and desiccated thyroid. But the evidence I present shows that the falsehoods are, indeed, false.
Meta-analyses or reviews examine a facet of medicine. These reviews start by searching literature and examining the selected literature for subject selection and continue with experimental methods, data analyses, and conclusion. All of these must logically support the current medical guidelines on hypothyroidism. The meta analyses in question DO NOT.
By way of ignoring 98% of the available relevant studies, the various authors summarily dismissed the 60-year old warnings that L-T4 monotherapy did not mitigate the symptoms of hypothyroidism in all patients,[40,41] summarily dismissed the 55-year old potential for these symptoms to exist in spite of “normal” thyroid test results, summarily dismissed the 45-year old discoveries of the responsible physiology, [191,192]summarily dismissed a long term study using natural desiccated thyroid to care for patients failed by endocrinology. and summarily dismissed the patient counterexamples in medical science history.[ 25,41]
The good news for the majority of patients is the meta-analyses [187-188] DO support the L-T4 monotherapy for deficient secretion by the thyroid GLAND. The bad news for endocrinology is there is no factual support in the meta-analyses to apply the L- T4 monotherapy to post-thyroid physiology.
One should also note the juxtaposition of the CONCLUSION with the CONTEXT of the meta-analysis. The CONTEXT states: In some patients, symptoms of hypothyroidism persist despite therapy with T(4) yet their CONCLUSION states: T(4) monotherapy should remain the treatment of choice for clinical hypothyroidism,which suggests that endocrinology insists that 15% of those treated with L-T4 monotherapy should simply continue to suffer.
As far as the CCG statement There has never been a direct comparison of these two treatments their statement is FALSE.
TPA sent the following list of 35 studies to the NHS UKMi by way of a rebuttal to their Q and A What clinical evidence is there to support the use of Armour thyroid or desiccated thyroid extract? 
Studies using Armour Thyroid/Natural Thyroid Extract-v-levothyroxine-only Therapy:
- Studies using ‘Armour Thyroid’ per se in three of 12 studies.[193-195]
- Nine further studies reporting direct comparison of the two forms of treatment i.e. natural -v- synthetic thyroxine only.[196-204]
- Studies that Established the Clinical Benefits of NDT.[205-225]
- The Therapeutic Equivalence of NDT, T4 and T3. [174-177]
The CCG have rejected these studies 
CCG: These statements emphasise the lack of evidence to demonstrate the safety and efficacy of NDT.
TPA: See evidence cited above.
CCG: Given this information, I hope you understand why the prescribing of NDT is not supported locally. The same advice will be given to all GP’s in the ******* and ********* area.
TPA: If the statements written by the CCG were correct, then it would be understandable why the prescribing of NDT is not supported locally for ALL patients suffering symptoms of hypothyroidism. However, there is much evidence to prove that their some of their statements are not only misleading, some are incorrect and they have ignored much evidence, and continue to state – it doesnt exist. Also, by the CCGs giving such misleading and incorrect information to all the GPs in their area this has the potential to cause yet further harm to their patients who need the prescription of some form of the active T3, either synthetic or natural thyroid extract. The CCGs are also taking away a doctors autonomy to prescribe what s/he believes is the most appropriate treatment for his/her patient.
The basic issues raised by this Clinical Commissioning Group are (1) the stability of natural desiccated thyroid, (2) its safety and (3) its effectiveness as a form of treatment for ALL patients suffering symptoms of hypothyroidism.
Considerable evidence that bears on these issues is readily available some set out above. Yet this local CCG has cited virtually none of it as to the reason(s) it has now decided to give Armour Thyroid, WP Thyroid, Erfa Thyroid and Nature Throid a black light and therefore, an excuse for their refusal to fund it for those patients who need it.
Regarding the Duties of a Doctor Registered with the General Medical Council, it appears that the Doctors at the this local CCG Committee have taken no account of such Duties as, (1)Make the care of your patient your first concern, (2) Keep your professional knowledge and skills up to date, (3) Be honest and open and act with integrity etc
When faced squarely and considered without prejudice, the evidence given in this rebuttal leads to conclusions diametrically opposed to those of this local CCG Committee
Finally, please note this instigation of modern medical philosophy by Giovanni Battista Morgagni: “Symptoms are the cries of suffering organs.”  The local CCGs, the BTA, the RCP, etc. recommend that these cries be ignored in favor of the proscription of the very therapy needed to mitigate this suffering.
5. Steven L. Richheimer, Charlotte B. Jensen. Response to Liothyronine and Levothyroxine in Armour Thyroid?: 1987.Journal of Pharmaceutical Sciences. Volume 76, Issue 4. Pages 346-347
6. Krantz JC Jr., “New Drugs and the Kefauver-Harris Amendment”, J New Drugs, 1966, Mar-Apr;6(22):77-9
7. Krantz JC Jr., “The Kefauver-Harris amendment after sixteen years,” Mil Med. 1978 Dec;143(12):883.
11. Armour website: http://www.armourthyroid.com/
13. Nature-throid/WP Thyroid Website: http://rlclabs.com/
14. NP by Acella Website: http://www.acellapharma.com/index.php
15. Thyroid by Erfa Website (Canada): http://www.eci2012.net/
19. The Royal College of Physicians. The diagnosis and management of primary hypothyroidism. Retrieved from: [http://dx.doi.org/10.1210/jc.2012-4107
29. Pepper GM, Casanova-Romero PY (2014) Conversion to Armour Thyroid from Levothyroxine Improved Patient Satisfaction in the Treatment of Hypothyroidism. J Endocrinol Diabetes Obes 2(3): 1055
30. Joffe R, Blank DW, Post RM, Uhde TW. Decreased triiodothyronines in depression: A preliminary report. BIOLOGICAL PSYCHI 1985; 20: 922-925.
31. Cooke RG, Joffe RT, Levitt AJ. T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. J CLIN PSYCHI 1992; 53, 1 (Jan): 16-18.
32. Gelenberg AJ. T3 + T4 = success. BIOLOGICAL THERAPIES IN PSYCHINEWS-LTR 1992; 15, 4 (April): 14.
33. Dommisse J. T3 is at least as important as T4 in all hypothyroid patients.J Clin Psychiatry. 1993 Jul;54(7):277-9.
34. Whybrow PC (1994): The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. Acta Medica Austriaca 21:47-5
35. CHOPRA IJ: Euthyroid sick syndrome: is it a misnomer? J Clin Endocrinol Metab 82: 329-334, 1997
36. Sjberg S, Eriksson M, Werner S, Bjellerup P, Nordin C. L-thyroxine treatment in primary hypothyroidism does not increase the content of free triiodothyronine in cerebrospinal fluid: a pilot study.Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. firstname.lastname@example.org. Scand J Clin Lab Invest. 2011 Feb;71(1):63-7.
37. Leslie J. De Groot. Dangerous Dogmas in Medicine: The Nonthyroidal Illness Syndrome. The Journal of Clinical Endocrinology & Metabolism January 1, 1999 vol. 84 no. 1 151-164
38. Dr. E. Chester Ridgway, Director of Endocrinology at the University of Colorado Health Sciences Center, Equivalence of Levothyroxine Sodium Products, Joint Public Meeting (Cosponsored with the American Thyroid Association, The Endocrine Society, and the American Association of Clinical Endocrinologists) Monday, May 23, 2005, pages 144
39. Baisier, WV, Hertoghe, J., B, Eekhaut, W., Thyroid Insufficiency? Is Thyroxine the Only Valuable Drug?, Journal of Nutritional and Environmental Medicine, Vol. 11, No. 3, September 2001, pages 159-166
40. Means JH: Lectures on the thyroid. Cambridge, MA. Harvard University Press. 1954; 48-4
41. Kirk E, Kvorning SA, Acta Med. Scandinav., Suppl. 184. pp 3-83. 194
42. Devlin WF, Watanabe H. Thyroxin-triiodothyronine concentrations in thryoid powders. J Pharm Sci. 1966 Apr;55(4):390-3
43. 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):97-10
44. 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
45. 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
46. Blackburn CM, McConahey WM, Keating FR Jr, Albert A. Calorigenic effects of single intravenous doses of l-triiodothyronine and l-thyroxine in myxedematous persons. J Clin Invest. 1954 Jun;33(6):819-24
47. Gross J, Pitt-Rivers R. Physiological activity of 3:5:3′-L-triiodothyronine. Lancet. 1952 Mar 22;1(12):593-4
48. Gross J, Pitt-Rivers R. 3:5:3′-triiodothyronine. 2. Physiological activity. Biochem J. 1953 Mar;53(4):652-7
49. Burroughs V, Shenkman L. Thyroid function in the elderly. Am J Med Sci. 1982, 283 (1): 8-17
50. 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
51. Tulp OL and McKee TD Sr. Triiodothyronine neogenesis in lean and obese LA/N-cp rats. Biochem Biophys Res Communications. 1986; 140 (1): 134-42
52. Katzeff HI, Selgrad C. Impaired peripheral thyroid hormone metabolism in genetic obesity. Endocrinology. 1993; 132 (3): 989-95
53. Croxson MS and Ibbertson HK. Low serum triiodothyronine (T3) and hypothyroidism in anorexia nervosa. J Clin Endocrinol Metab. 1977; 44: 167-73
54. 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
55. Opstad PK, Falch D, ktedalen 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
56. Walfish PG. Triiodothyronine and thyroxine interrelationships in health and disease. Can Med Ass. J 1976, 115: 338-4
57. Feyes D, Hennemann G and Visser TJ. Inhibition of iodothyronine deiodinase by phenolphtalein dyes. Fed Eur Biomed Sci. 1982; 137(1):40-4
58. 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
59. 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
60. Paier, B; Hagmller, K; Noli, MI; Gonzalez Pondal, M; Stiegler, C; Zaninovich, AA. Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver.J Endocrinol. 1993; 138(2):219-22
61. arregrd L, Lindstedt G, Schtz A, Sllsten G. Endocrine function in mercury exposed chloralkali workers. Occup Envir Med. 1994; 51: 536-40
62. Burger AG, Lambert M, Cullen M. Interfrence de substances mdicamenteuses dans la conversion de T4 en T3 et rT3 chez lhomme. Ann Endocrinol (Paris). 1981,42:461-9
63. Grussendorf M, Hfner M. Induction of the thyroxine to triiodothyronine converting enzyme in rat liver by thyroid hormones and analogs. Clin Chim Acta. 1977;80:61-6
64. 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
65. 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
66. Schrder-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
67. Gavin LA, Mahon FA, Moeller M. The mechanism of impaired T3 production from T4 in diabetes. Diabetes. 1981;30:694-9
68. 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
69. 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
70. Arthur JR, Nicol F, Beckett GJ. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr Suppl. 1993; 57:236S-9S
71. Beard J, Tobin B, and Green W. Evidence for thyroid hormone deficiency in iron-deficient anemic rats. J Nutr. 1989;772-8
72. 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
73. 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
74. Westgren U, Ahren B, Burger A, Ingemansson S, Melander A. Effects of dexamethasone, desoxycorticosterone, and ACTH on serum concentrations ot thyroxine, 3,5,3-triiodothyronine and 3,3,5-triiodothyronine. Acta Med Scand. 1977;202 (1-2): 89-92
75. 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
76. 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
77. Aizawa T, Yamada T. Effects of thyroid hormones, antithyroid drugs and iodide on in vitro conversion of thyroxine to triiodothyronine. Clin Exp Pharmacol Physiol. 1981; 8: 215-25
78. 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
79. Hays MT. Absorption of oral thyroxine in man. J Clin Endocrinol Metab. 1968; 28 (6):749-56
80. 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
81. Hubbard WK. FDA notice regarding levothyroxine sodium. Federal register. 1997; 62(157): 1-10
82. 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
83. 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
84. 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%))
85. 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%)
86. Nesher G, Zion MM. Recurrent ventricular tachycardia in hypothyroidism==report of a case and review of the literature. Cardiology. 1988;75(4):301-6
87. 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
88. 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
89. 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
90. 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
91. 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
92. 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
93. 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
94. 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)
95. 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 =
96. Reza MJ, Abbasi AS. Congestive cardiomyopathy in hypothyroidism. West J Med. 1975 Sep;123(3):228-30
97. 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)
98. 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
99. Klein I, Ojama K. In: Werner & Ingbars The Thyroid, ed. Braverman LE & Utiger RD, Lippincott-Raven Publishers, Philadelphia, 1996, 62: 799-804
100. 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
101. 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
102. Wortsman J, Premachandra BN, Chopra IJ, Murphy JE. Hypothyroxinemia in cardiac arrest. Arch Intern Med. 1987 Feb;147(2):245-8
103. 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
104. 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
105. 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
106. 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)
107. Barnes BO. Prophylaxis of ischaemic heart-disease by thyroid therapy. Lancet. 1959 Aug 22;2:149-52
108. 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
109. 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
110. 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
111. Perk M, ONeill BJ; The effect of thyroid therapy on angiographic artery disease progression. Can J Card. 1997;13(3):273-6
112. Zondek H. Myxedema Heart. Munch Med Wochenschr. 1918, 65: 1180-3Novitzky 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.
113. 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
114. 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
115. 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
116. 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.
117. Baisier, WV, Hertoghe, J., B, Eekhaut, W., Thyroid Insufficiency? Is Thyroxine the Only Valuable Drug?, Journal of Nutritional and Environmental Medicine, Vol. 11, No. 3, September 2001, pages 159-166
118. Hertoghe T, Lo Cascio A., Hertoghe J. Considerable improvement of hypothyroid symptoms with two combined T3-T4 medication in patients still symptomatic with thyroxine treatment alone. Anti-Aging Medicine (Ed. German Society of Anti-Aging Medicine-Verlag 2003) 2004; 32-43
119. Alan R. Gaby, MD Alternative Medicine Review Volume 9, Number 2, 2004
121. Joint Committee on Higher Medical Training, Higher Medical Training Curriculum for Endocrinology and Diabetes Mellitus, 2003
122. Bassett JH, OShea PJ, Sriskantharajah S, et al: Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism. Mol Endocrinol, 2007; 21: 1095-1107.
123. J Clin Endocrinol Metab 1996 Mar;81(3):1232-6, “Prevention of bone loss induced by thyroxine suppressive therapy in postmenopausal women: the effect of calcium and calcitonin.”
124. Svanberg E, Healey J, Mascarenhas D. Anabolic effects of rhIGF-I/IGFBP-3 in vivo are influenced by thyroid status. Eur J Clin Invest. 2001 Apr;31(4):329-36.
125. Barnes B, Galton L: Hypothyroidism: The Unsuspected Illness. New York, NY. Harper & Row. 1976.
126. Tseng KH, Walfish PG, Persaud JA, Gilbert BW. Concurrent aortic and mitral valve echocardiography permits measurement of systolic time intervals as an index of peripheral tissue thyroid functional status. J Clin Endocrinol Metab. 1989 Sep;69(3):633-8
127. 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
128. 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%))
129. 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%)
130. Nesher G, Zion MM. Recurrent ventricular tachycardia in hypothyroidism==report of a case and review of the literature. Cardiology. 1988;75(4):301-6
131. 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
132. 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):657-63
133. 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
134. 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
135. 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
136. 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 44
137. 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
138. 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)
139. 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
140. 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 27. Reza MJ, Abbasi AS. Congestive cardiomyopathy in hypothyroidism. West J Med. 1975 Sep;123(3):228-30
141. 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
142. 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)
143. 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
144. Klein I, Ojama K. In: Werner & Ingbars The Thyroid, ed. Braverman LE & Utiger RD, Lippincott- Raven Publishers, Philadelphia, 1996, 62: 799-804
145. 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
146. 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
147. 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-
148. Wortsman J, Premachandra BN, Chopra IJ, Murphy JE. Hypothyroxinemia in cardiac arrest. Arch Intern Med. 1987 Feb;147(2):245-8
149. Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L’Abbate A, Donato L. Low-T3 11;107(5):708-13
150. Dorr M, Volzke H. Cardiovascular morbidity and mortality in thyroid dysfunction. Minerva Endocrinol. 2005 Dec;30(4):199-216
151. 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
152. 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).
153. 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 developed to replace an earlier resistance).
154. Barnes BO. Prophylaxis of ischaemic heart-disease by thyroid therapy. Lancet. 1959 Aug 22;2:149- 52
155. 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
156. 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
157. 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
158. Perk M, ONeill BJ; The effect of thyroid therapy on angiographic artery disease progression . Can J Card. 1997;13(3):273-6
159. Zondek H. Myxedema Heart. Munch Med Wochenschr. 1918, 65: 1180-3
160. 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
161. 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.
162. 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
163. Holland FW, Brown PS, Clark RE. Acute severe postischemic myocardial depression reversed by triiodothyronine. Ann Thorac Surg 1992 54: 301-305
164. 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
165. 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):141-62
166. 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):1587-9
168. Barnes BO. “Is there a third hormone in the thyroid gland? Which preparation should be used for treatment?” J Int Acad Prev Med 1982; November:38-39.
169. Loeser A. “Thyroid and ovary”. Journal of the American Medical Association 1935;104: 870.
170. Morse M. “The effective principle in thyroid accelerating involution in frog larvae”. J Biol Chem 1914;19:421-429
171. Csaba G, Nemeth G. “Enhancement of the sensitivity of Tetrahymena to a second hormonal influence by hormone pre-treatment”. Acta Biol Med Ger 1980;39:1027-1030
172. Shames, RL, Shames, KH, Thyroid Power: 10 Steps to Total Health, Harper Collins Publishers, New York, 2001.
173. Rothfeld, G.S., Romaine, D.S., “Thyroid Balance: Traditional and Alternative Methods for Treating Thyroid Disorders”, Adams Media Corporation, Avon, Massachusetts, USA, 2003.
174. Brownstein, D., Overcoming Thyroid Disorders, Medical Alternatives Press, 2002.
175. Lombardi, A.Lanni, A.Silvestri,E. de Lange, P.Goglia, F.Moreno,M. 3, 5Diiodothyronine: Biological Actions and Therapeutic Perspectives. pp.255-265 (11)
176. Lanni A et.al.”3,5-diiodo-l-thyroxine (T2) reduces adiposity and body weight gain in rats by increasing fatty acid ocidation”. Abstracts.2004. European thyroid Association Annual Meeting.
177. Goglia et al. FEBS Letters. 452, 115-120 (1999)
178. Lombardi et al. Biochem J. 330, 521-526 (1998).
179. Lombardi et al. Endocrinology. 141, 1729-1734 (2000)
180. Ball et al. J Molec Endocrinology. 19, 137-147 (1997).
181. Ball et al. J Molec Endocrinology. 19, 137-147 (1997).
182. Assunta Lombardi, Antonia Lanni, Pieter de Lange, Elena Silvestri, Paola Grasso, Rosalba Senese, Fernando Goglia and Maria Moreno. “Acute administration of 3,5-diiodo-l-thyronine to hypothyroid rats affects bioenergetic parameters in rat skeletal muscle mitochondria”.FEBS Letters, Volume 581, Issue 30, 22 December 2007, Pages 5911-5916
183. J. Kvetny. Horm. Metab. Res. 24:322-325, 1992.
184. Moreno M, et al. “Effect of 3, 5-Diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats.” Life Sciences, Volume 62, No.26, pp. 2369-2377, 1998.
185. Horst C, et al. “3, 5-Di-iodo-L-thyronine suppresses TSH in rats in vivo and in rat pituitary fragments in vitro.” J Endocrinol 1995 May;145(2):291
187. Escobar-Morreale, H.F., Botella-Carretero, J.I., Escobar del Rey, F., et al.: Review: Treatment of hypothyroidismwith combinations of levothyroxine plus liothyronine. J. Clin. Endocrinol. Metab., 90(8):4946- 4954, 2005.
188. Grozinsky-Glasberg, S., Fraser, A., Nahshoni, E., et al.: Thyroxine-triiodothyronine combination therapyversus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials.J. Clin. Endocrinol. Metab., 91:2592-2599, 2006
189. Joffe RT, Brimacombe M, Levitt AJ, et al, Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and meta-analysis, Psychomatics 2007; 48:379-384
190. Goldberg M, The Case For Euthyroid Hypometabolism, Am J Med Sc 1960:479-493
191. 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, 1967;27:279
192. Braverman LE, Ingbar SH, Keinwem S, Conversion of Thyroxine (T4) to Triiodothyronine (T3) in Athyreotic Human Subjects, J Clin Invest. 1970;49(5):855864
193. Krenning, E.P., Docter, R., Visser, T.J., et al.: Replacement therapy with L-thyroxine: serum thyroid hormone and thyrotropin levels in hypothyroid patients changing from desiccated thyroid to pure thyroxine substitution therapy. Neth. J. Med., 28(1):1-5, 1981.
194. Singh, S.P., Feldman, E.B., and Carter, A.C.: Desiccated thyroid and levothyroxine in hypothyroidism: comparison in replacement therapy. N.Y. State J. Med., 72(9):1045-1048, 1972.
195. Sawin, C.T., Hershman, J.M., Fernandez-Garcia, R., et al.: A comparison of thyroxine and desiccated thyroid in patients with primary hypothyroidism. Metabolism, 27(10):1518-1525, 1978.
196. LeBoff, M.S., Kaplan, M.M., Silva, J.E., et al.: Bioavailability of thyroid hormones from oral replacement preparations. Metabolism, 31(9):900-905, 1982.
197. Lavietes, P.H.. and Epstein, F.H.: Thyroid therapy of myxedema: A comparison of various agents with a note on the composition of thyroid secretion in man. Ann. Intern. Med., 60:79-87, 1964.
198. Gorowski, T., Pucilowska, J., and Wernic, K.: Comparative effects of desiccated thyroid gland and sodium salt of L-thyroxine in the treatment of hypothyroidism.Pol. Tyg. Lek., 44(32-33):768-770, 1989.
199. Felt, V. and Nedvidkova, J.: Comparison of treatment with L-thyroxine and a dried thyroidgland preparation in patients with hypothyroidism. Vnitr. Lek., 28 (11):1067-1073, 1982
200. Wartofsky, L.: Combined levotriiodothyronine and levothyroxine therapy for hypothyroidism: are we a step closer to the magic formula? Thyroid, 14(4):247- 248, 2004
201. Kosowicz, J., Horst-Sikorska, W., Lacka, K., et al.: Outcome of treating hypothyroidism with thyreoideum. Pol. Tyg. Lek, 48(27-28):599-602, 1993.
202. Warszawie, C.M.K.P.: Treatment of hypothyroidism with L-thyroxine. Pol. Tyg. Lek, 48(27-28):605-608, 1993.
203. McGavack, T.H. and Reckendorf, H.K.: Therapeutic activity of desiccated thyroid substance, sodium Lthyroxine and D, L-triiodothyronine: a comparative study. Am. J. Med., 20:774-777, 1956
204. Baisier, W.V., Hertoghe, J., and Eeckhaut, W.:Thyroidinsufficiency: is thyroxine the only valuable Drug? J. Nutr. Environ. Med., 11:159-166, 2001.
205. Gautam Das, Shweta Anand & Parijat De. Does synthetic thyroid extract work for everybody? Endocrine Abstracts (2007) P316
206. Alan R. Gaby, MD. Sub-laboratory Hypothyroidism and the Empirical use of Armour Thyroid. (Altern Med Rev 2004;9(2):157-179)
207. Lowe, J.C.: Natural desiccated thyroid: Guttlers false claim about It. Thyroid Science 4(9):C1-6, 2009
208. Novak, Edmund A. M.D.; Holthaus, Joseph M. M.D.; Ogborn, Richard O. M.D: Clinical Study of Levo-Thyroxine and Aged Desiccated Thyroid in Euthyroid Subjects: American Journal of the Medical Sciences: March 1964
209. Thompson, W.O., McLellan, L.L., Thompson, P.K., et al.: The rates of utilization of thyroxine and of desiccated thyroid in man: the relation between the iodine in desiccated thyroid and thyroxine. Arch. Intern. Med., 1932.
210. Boothby, W. M., Sandiford, I., Sandiford, K., et al.: Abstract of Communication to the XIIth International Physiol. Congress held at Stockholm, Aug. 3-6, 1926. Skandinav. Archiv. 1926, xlix, 99. Metabolism studies showing the effect of desiccated thyroid and thyroxin on a patient with myxedema.
211. Thompson, W.O., Nadler, S.B., Taylor, S. G., III, and Thompson, P. K.: The calorigenic action of various thyroid derivatives. J. Clin. Invest. (Proc.), 13:690, 1934.
212. Foster, G. L., Palmer, W. W., and Leland, J. P.: A comparison of the calorigenic potencies of l-thyroxine, dl-thyroxine, and thyroid gland, with a note on the thyroxine content of the acid-soluble fraction of the peptic digest of thyroid protein. J. Biol. Chem., 115:467, 1936
213. Thompson, W. O., Thompson, P. K., Brailey, A. G., et al.: The calorigenetic action of thyroxin at different levels of basal metabolism in myxedema. J. Clin. Invest., 7(3): 437463, 1929.
214. Sturnick, M.I. and Falcon-Lesses, M.: A comparison of the effect of desiccated thyroid and sodium levothyroxine on the serum protein-bound iodine. New Engl. J. Med., 264:609, 1961.
215. Sisson, J.C.: Principles of, and pitfalls in, thyroid function tests. J. Nuclear Med., 6:853-901, 1965.
216. Robertson, J.D. and Kirkpatrick, H.F.W.: Changes in basal metabolism, serum protein-bound iodine and cholesterol during treatment of hypothyroidism with oral thyroid and l-thyroxine sodium. Brit. Med. J., March 22, 1:624, 1952.
217. Gilman, A.G. and Murad, F.: Thyroid and antithyroid drugs. In The Pharmacologic Basis of Therapeutics, (ed 5). Edited by L.S. Goodman and a. Gilman, New York, MacMilIan, 1975, p.1398.
218. Means, J.H., DeGroot, L.J., and Stanbury, J.B.: The Thyroid and Its Diseases, 3rd edition. New York, McGraw-Hill, 1963, p. 334.
219. Werner, S.C.: Treatment of hypothyroidism. In The Thyroid, 3rd edition. Edited by S.C. Werner and S.H. Ingbar, New York, Harper and Row, 1971, p.834.
220. Daughaday, W.H.: The adenohypophysis. In Textbook of Endocrinology, 5th edition. Edited by R.H. Williams, Philadelphia, Saunders, 1974, p.60.
221. Lowe, J.C.: Stability, effectiveness, and safety of desiccated thyroid vs levothyroxine: rebuttal to the British Thyroid Association. Thyroid Science, 4(3):C-1-12, 2009.
222. Frederick L. Benoit.ieutenant Commander, MC, MC, USN: Treatment of Riedel’s Thyroiditis With Desiccated Thyroid.Endocrine Clinic and Medical Service, U.S. Naval Hospital,Oakland..Submitted July 14, 1964.
223. Beverley Strisower, A.B.,John W Gofman, MD., Elmer Galioni, MD.,Joshua H Rubinger, M.D.,Georgfe W OBrien M.D. and Alexander Simon, M.D. Effect of Long-Term Administration of Desiccated Thyroid on Se
224. Lipoprotein and Cholesterol Levels.The Journal of Clinical Endocrinology & Metabolism January 1, 1955 vol. 15 no. 1 73-80
225. George S. Serif and Alan K Brevik.: ” Effects of Butyl-4-hydroxy-3,5-diiodobenzoate on the Conversion of p-carotene to Vitamin A in the Rat.” The Journal of Biological Chemistry. Vol. 235, No. 8, August 1960