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.

TPA Rebuttal to BTA Statement on Armour Thyroid

March 2008

The Thyroid Patient Advocacy-UK (TPA-UK) Response to:

“A Statement from the British Thyroid Association Executive Committee on Armour Thyroid” “As often in the history of science, the biggest obstacle in finding the truth is not the difficulty in obtaining data, but the bias of the investigators on what data to chase and how to interpret them.”

Peter H. Duesberg, PhD, Inventing the AIDS Virus Washington, DC, Regnery Publishing, Inc., 1996


Thyroid Patient Advocacy-UK (TPA-UK) disagrees with many of the statements made by the Executive Committee of the British Thyroid Association (BTA) on natural desiccated porcine thyroid extract (Armour Thyroid, USP). TPA-UK are very concerned that the BTA continue to advise that L-thyroxine (T4) replacement remains the treatment of choice despite the amount of evidence contrary to their opinion, showing it to be ineffective in relieving many patients’ symptoms.1

Conventional medical practitioners have made no attempt to evaluate the evidence regarding the use of natural thyroid hormone, and their wholesale dismissal of the concept represents, at least in part, a biased attitude.

History of Thyroid Hormone Treatments

In 1875, Sir William W. Gull published his study of five women suffering from what he called myxoedema.2 Sixteen years later, a successful attempt was made to implant a sheep thyroid gland under the skin of a woman suffering from myxoedema. This case was reported in the journal La Semaine Medicale by Betancourt, Lisbon, Portugal on 18th August 1890.3 One year later, myxoedema was successfully treated with enteral and parenteral administration of both thyroid glands and thyroid extract.3, 4, 5

Immediate improvement was seen after implantation of the sheep thyroid gland, and it became obvious that the beneficial clinical effect was due to a biological active compound released by the implanted sheep thyroid gland into the patient. In July 1891, based on a review of the literature, George R. Murray presented his observations at the Annual Meeting of the British Medical Association (BMA) of a female patient with myxoedema who had been treated successfully with hypodermic injections of extract from the thyroid glands of sheep.3

One year after Murrays publication, physicians Fox and MacKenzie reported that oral administration of fresh sheep thyroid gland and thyroid extract were effective in reversing the signs and symptoms of hypothyroidism in a female patient.4, 5 The reports from MacKenzie and Fox were published back-to-back in the October 1892 issue of the British Medical Journal (BMJ).

Following this publication, oral preparations of thyroid extracts became available and were widely used to treat hypothyroidism successfully.

Based on his research, Bauman (1895) concluded that the active substance in the thyroid gland contains iodine. He attempted, unsuccessfully, to hydrolyze thyroidal proteins in order to isolate the active principle. Following Baumans publication in 1895 reporting high concentrations of iodine tightly bound to proteins in extracts of the thyroid gland, thyroid extracts were standardized to contain 0.2% iodine in order to maintain equal potency of different preparations.6

In 1915, Kendall succeeded in hydrolyzing thyroid proteins into simpler constituents.7 Further purification yielded a biologically active iodine-containing substance, which was crystallized into a pure form. Kendall called this crystallized product thyroxine. He wrote: “In brief, the compound containing iodine, the presence of which, as a normal constituent of the thyroid, as foretold by Baumann 19 years ago, has been isolated in pure crystalline form, and further, it has been shown that this compound is the substance in the thyroid which is responsible for the physiologic activity of the gland.”6 Unfortunately, Kendall incorrectly concluded that the structure was triiodohexahydroxyindole propionic acid.7

In 1926, Dr. C. R. Harrington of University College London showed that thyroxine is the tetraiodo derivative of thyronine, and he was able to synthesize the active compound.8

The Deliberate Hoax

Thyroid extracts continued their popularity and were not affected by the introduction of synthetic thyroxine in the 1930s until a hoax batch of thyroid extract, containing only iodine with no thyroid hormone, was shipped to Europe and the US in 1963, with the goal of discouraging the use of thyroid extracts. This hoax made thyroxine the only eligible thyroid preparation for hypothyroidism because the iodophobic domino effect of the 1948 Wolff-Chaikoff publication prevented physicians from supplementing their patients with iodine.9

Many doctors were reluctant to switch to thyroxine only, preferring to prescribe the desiccated gland. They were, however, eventually persuaded to change their allegiance.

In 1969, Dr. Wolff from the National Institute of Health published his paper titled, “Iodide goiter and the pharmacologic effects of excess iodide”.9, 10 In 1970, Goodman and Gilman stated, This episode gave thyroid a bad name because several publications about the unreliability of thyroid appeared before the hoax was uncovered.11 There was widespread concern that the effects of this “drug” were not consistent with previous clinical experience and so all thyroid extract was labelled “unreliable”. Although the hoax was uncovered seven years later and The Medical Letter in 1973 maintained that desiccated thyroid extract had never been unreliable, mud sticks, and doctors started using synthetic l-thyroxine.10

To quote Derry “. . . by 1976 about half (52%) of the prescriptions written for thyroid hormone in the United States were for desiccated thyroid or other natural products.12 The best pharmacological authorities confirmed desiccated thyroid remains a remarkably clinically, predictable safe and effective preparation which is well absorbed”. So why the continued misinformation perpetrated by the BTA?

BTA Statement

A. Armour Thyroid contains both thyroxine (T4) and tri-iodothyronine (T3) extracted from the thyroid gland of pigs. One grain, about 60 mg, of desiccated pig thyroid extract contains about 38mcg of T4 and 9mcg of T3, a ratio of around 4 to 1. The normal concentration of these hormones in the human thyroid is, however, at a ratio of 14 to 1. In other words, Armour thyroid extract contains excessive amounts of T3 relative to T4 when used to replace thyroid hormone in man. Moreover, as pig thyroid contains other substances apart from T4 and T3, Armour Thyroid is not a pure preparation of thyroid hormones. Historically, extracts of animal thyroid glands were the only way to treat thyroid underactivity, but since the 1950s pure synthetic thyroid hormones have been available in tablet form (thyroxine sodium [T4] and liothyronine [T3]).

“All thyroid hormone products, both animal-derived and synthetic, are 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”.13 Therefore, it is prudent for both doctors and patients to be vigilant for sub-potent tablets or capsules.

There is no evidence showing that thyroxine sodium and liothyronine are more stable than Armour thyroid. The BTA statement causes confusion for doctors, often to the detriment of patients. It is the belief of TPA-UK that such statements by the BTA should be evidence-based and TPA therefore supply herewith the references to support their claims.

It appears that some NHS doctors do not recommend Armour thyroid because they believe the amount of thyroid hormone varies between batches and/or they believe the higher ratio of T3 to T4 in Armour could be harmful or cause adverse reactions. The evidence does not support such reasoning, and in fact the variation of thyroid hormone in Armour is minimal and well controlled (maximum 5-10 %) as specified by the US FDA.14, 15

There are many thyroid extract preparations and the trademark Armour Thyroid should not be used as a generic name for these. There is much evidence that Armour Thyroid is the most reliable of the desiccated thyroid preparations in the US.15, 16, 17, 18, 19

Evidence is presented in the Empirical use of Armour thyroid by Gaby that many people have hypothyroidism undetected by laboratory thyroid-function tests, and cases are reported to support the empirical use of Armour Thyroid. Clinical evaluation can identify individuals with sub-clinical hypothyroidism that is likely to benefit from thyroid-replacement therapy. In a significant proportion of cases, 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 desiccated thyroid has produced better clinical results than levothyroxine. 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.19

Armour Thyroid does have a higher amount of T3 compared to T4 than the relative amounts of T3 to T4 secreted by the human thyroid gland, however it is well documented that Armour is often more effective and is better tolerated than synthetic preparations of T4, T3 and T4/T3 combination.20 This is because the T3 in natural thyroid extract is absorbed more slowly than synthetic (purified, unbound) T3.21

The normal thyroid gland contains approximately 200 mcg of T4 per gram of gland, and 15 mcgs of T3 per gram. The ratio of these two hormones in the circulation does not represent the ratio of 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.22

A similar ratio can be obtained by prescribing both Armour and synthetic thyroxine, although clinical response and symptom control should take precedence over a theoretical ideal. Perhaps the ultimate form of thyroxine for difficult patients is whole thyroid extracted from nimals, such as Armour thyroid tablets.22, 23, 24

The long history of successful use thyroid extract in America has seen natural thyroid extract products successfully compete with the heavily promoted synthetic T4 and T3 preparations. Not only are whole glandular extracts often superior to T4 for the treatment of hypothyroidism, but there is evidence to suggest that such products are also superior to combined T4/T3 preparations.25. 26 Shames and Shames report a patient who was treated unsuccessfully with a combination of T4 and T3 who experienced a dramatic improvement when switched to Armour thyroid extract.26 When synthetic T4 and T3 first became available, Arem reports the considerable difficulties he experienced when switching patients from thyroid extracts to the new synthetic preparations.25 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.”

Since at least a third of treated hypothyroid patients whose blood tests have been restored to “normal” continue to have symptoms, therefore modern thyroid treatment is often unsuccessful, a fact which is hardly surprising given the fact that triiodothyronine (T3) is the crucially important active thyroid hormone; and the commonly seen failure to convert T4 to T3 (and also, to a lesser extent T2) will result in an unsatisfactory treatment outcome. 25, 26, 27, 28 This underlines the urgent need to rethink methods of thyroid treatment. Clearly, much greater priority must be given to a symptomatic approach and the importance of how the patient feels, given the relative ineffectiveness of T4 and the dubious usefulness of the serum TSH test alone for diagnosis. Over reliance on laboratory tests, without clinical evaluation, may lead to considerable diagnostic errors.29, 30, 31, 32

Hypothyroid patients who remained polysymptomatic on T4 treatment who were switched to Armour thyroid extract became biochemically euthyroid and completely symptom-free.33

Since thyroid replacement therapy should aim to reproduce as closely as possible the natural secretions of the thyroid gland, there should be more support for the use of whole thyroid extracts. To this end the effectiveness of whole thyroid extract versus synthetics should be compared in clinical trials, especially involving problematic patients.

BTA Statement:

B. The concentration of thyroid hormones in Armour Thyroid USP is regulated by the manufacturer to United States Food and Drug Administration (FDA) standards. Despite this, there have been significant problems with the stability of Armour Thyroid in recent years, prompting a massive recall of tablets 1. Because of these stability problems with Armour Thyroid, there is potential for fluctuations in thyroid hormone levels in the blood of patients treated with Armour Thyroid. These fluctuations may be unpredictable and have adverse effects on patients health.

In a 2005, sample testing of several batches of Armour found that some of the samples were not maintaining full potency.34 These were manufactured between March and August 2003, and were set to expire between March and August of 2005. To avoid potential problems, it was decided to recall all the Armour made during that timeframe in 2003. A Forest Pharmaceuticals spokesperson stated that very little of the recalled product remained in circulation at that time. Interestingly though, other evidence has shown variation of T4 in synthetic thyroxine to be greater than 30% in some batches.34

In a 1980 study, a number of manufacturers other than Forest Pharmaceuticals had versions of desiccated thyroid that were found to be unreliable in potency. The amounts of T4 and T3 in Armour Thyroid, USP were found to be constant. Moreover, two-year old and fresh tablets of Armour Thyroid contained similar amounts of T4 and T3.16

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. 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.15

The single reference the BTA executive has used to support their Statement on Armour is the Federal Drugs Administration (FDA) withdrawal notice of Armour. 34 If this withdrawal is evidence against the use of Armour Thyroid, the same argument follows for synthetic thyroxine. There have been previous reports of many defects in the commercial T4 alone preparation over the years.35, 36 The FDAs letter to the manufacturers of Synthroid (Eltroxin UK) summarises 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.”36

In 2005, endocrinologists had expressed concern about the performance of levothyroxine sodium. As a result, FDA requested product stability data from manufacturers of all approved products manufactured between July 2003 and June 2005. In 2006, FDA presented the data at a joint meeting of the Endocrine and Metabolic Drugs Advisory Committee and the Advisory Committee for Pharmaceutical Sciences. The purpose of the meeting was to discuss the potency and stability of marketed levothyroxine products. In October 2007, FDA announced that it was tightening its potency specifications for all levothyroxine sodium to ensure the drug retained its potency over its shelf life. The FDA has taken this action in response to concerns that levothyroxine sodium potency may deteriorate prior to its expiration date.37

Many millions of patients throughout the world have used and continue to use natural thyroid extract. Before the advent of the TSH test in the early 1970s, patients used these products in much higher dosages than nowadays.38 There is no evidence to show that patients were harmed by these higher dosages.

Armour Thyroid is a combination T4/T3 treatment and there is evidence that combinations of synthetic T4/T3, or T3 alone treatments, result in greater improvement of clinical symptoms than T4 only treatment, which therefore supports the argument in favour of treating with T4/T3 combination.20, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50

Further evidence of the potential benefits of a combined T4/T3 treatment protocol

Adding T3 to T4 results in greater improvement of clinical symptoms and signs in hypothyroid patients.58

When T3 and T4 are both added to the food simultaneously with goitrogens, a much better prevention of goitre is obtained than when T4 alone is added, even at 7 times higher concentration.59

In humans, T4/T3 treatments have been shown to reduce serum cholesterol and increase the speed of the Achilles tendon reflexes better than T4 treatments alone.60

Several studies in rats rendered hypothyroid show that cellular euthyroidism is only obtained in the target organs if T3 is added to the classic T4 medication.61, 62

T3 is thought to be between four and five times as potent as T4.63, 64 The absorption of oral T4 can be variable (50 to 73%), contrasting with that of T3 that is more constant and efficient (95%).87, 88

TPA-UK wish to highlight the many conditions that may reduce the conversion of T4 to T3, e.g. aging, obesity, disease, stress, exercise, malnutrition, etc., potentially reducing the efficacy of a T4 alone treatment, and in which a natural or synthetic T4/T3 treatment may be more effective.51, 52, 53, 54, 55, 56, 57

There are also toxic substances such as phenols, cadmium, and mercury and medications such as propranolol, amiodarone and several others that may interfere by inhibiting the T4 to T3 conversion.65, 66, 67, 68, 69

Deficiencies in hormones, such asT3 itself, TSH, growth hormone, insulin, cortisone and certain trace elements such as selenium, iron, zinc, copper, iodine partially block this essential conversion step for thyroid function.70, 71, 72, 73, 74, 75, , 76, 77, 78, 79, 80, 81, 82, 83

On the other hand, excess hormones such as glucocorticoids, ACTH, oestrogens and some trace elements may slow down the conversion of T4 to T3.84, 85, 86

The Third Thyroid Hormone: 3, 5-diiodo-l-thyronine (T2)

Many endocrinologists believe there is little (or no) information about the other thyroid hormones 3, 5-diiodo-l-thyronine (T2) and monoiodothyronine (T1). This is not the case.

The manufacturers of Armour Thyroid to USP (Forest Pharmaceuticals) have done no studies into the specific amount of T2, T1, calcitonin or any other T hormones that are naturally occurring in the desiccated thyroid. Nothing has been removed in the processing.

BTA Statement:

C. 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.

There may be advantages to using Armour that are not related to its T3 content. Broda Barnes observed some patients treated with syntheticT4/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 Armour.89 This observation suggests a third active substance is secreted by the thyroid gland. The most likely candidate is diiodotyrosine(T2). Although little was known about the function of this compound in humans, the widely held assumption that it is metabolically inert may be incorrect. In a study of guinea pigs, oral administration of T2 prevented alterations in thyroid and pituitary function induced by oophorectom.90 Administration of T2 also accelerated the metamorphosis of tadpoles and enhanced the growth of the protozoan Tetrahymena. 91, 92

Whole thyroid extracts contain T4 and T3, and also T2 and T1, which also have hormonal activity.26, 28, 93, 94, 95, 96, 97, 98 .99 ,100, 101, 102, 103, 104 Notably, as we have seen, T2 is very active in its metabolic effects.26

T2 has been shown to increase hepatic oxygen consumption by about 30%. The authors of the study discovered that out of T4, T3 and T2, only T2 was active in stimulating rapid hepatic oxygen consumption. They concluded that it acts rapidly and directly through activation of the mitochondria.28

In another study, T3 and T2 were compared in terms of Resting Metabolism (RM) and on the oxidative capacity of tissues that are metabolically active (liver, muscle tissue, brown adipose tissue or BAT, and heart). What they found was that T2 had a dose-dependent effect, which increased RM and oxidative capacity. They found the greatest response to T2 was in the liver and in BAT. The effects again occurred rapidly and independently of protein synthesis. They stated that their results suggested isomers like T2 could be direct mediators of thyroid hormone regulation on energy metabolism.93, 94 A further study found increased hepatic oxidative capacity and thought this was due to a direct action upon the mitochondria by T2.95 Other studies had similar findings.96, 97

Yet another study showed the same thing: increased oxidative capacity and energy expenditure, causing the authors to suggest that T2 and T3 displayed similar effects.98 T2 was also shown to have a similar effect to that of T3 on lipid metabolism with T2 actually doing a little better in some tissue.99

Although there is little research in humans, some does exist. In one study, using human mononuclear blood cells, it was found that T2 increased the rate of respiration significantly.105 So, the efficacy appears to have been established. Can it significantly inhibit TSH like T3 and T4? The studies are conflicting, but one thing seems to be prevalent amongst them all TSH inhibition isnt nearly as severe with T2 as it is with T3.100

One study showed that T2 is 13% less inhibitory on TSH levels, as compared to T3.101

In yet another study, T3 and T2 suppressed TSH to similar levels; however, it took 15 mcg/100g body weight per day of T3 to accomplish this, while it took 200 mcg/100g body weight per day of T2 to accomplish the same thing. This means it took about 13 times more T2 to exert the same effect on TSH as T3.102

When researchers in another study administered 100 ug/kg of T3 and 800-1600 ug/kg of T2 the following occurred: T3 rapidly decreased serum TSH levels to within minimal levels after 24 hours. Seventy-two hours after application, TSH levels were still significantly lower than control levels. As far as the T2, TSH levels were transiently reduced and reached their lowest point at 24 hours and increased afterwards. Basal levels were reached 72 hours after an application. What they found after analysing the data was that there seemed to be a trend for a dose-dependent suppression of TSH by T2, which did not reach statistical significance. Furthermore, it appears as though it took 100 times more T2 than T3 to finally exert the same amount of TSH inhibition. Even using 400 times more T2 than T3, it appears that T3 only allows TSH to be inhibited to just a slight degree less than T2.103

BTA Statement

D. 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.

Armour Thyroid is no more likely to cause side effects than is a synthetic T4/T3 combination.151 Splitting the daily dose of Armour would obviate any potential concern about transient elevations of T3 levels.19

Thyroxine was introduced without any comparison with natural thyroid extract. The Medicines Control Agency (MCA) has continued its use without review. Given that levothyroxine is the cheaper medication (see below for cost of Armour), one has to question why the manufacturers would not wish to demonstrate equal effectiveness. Natural thyroid extract has been making patients better since 1894, long before the introduction of synthetic thyroxine. Thus, the burden of proof lies with the synthetic product to demonstrate it is as safe, effective and as consistent as Armour.15, 16

BTA Statement:

E. Armour Thyroid is not on the British National Formulary and is not a licensed therapy in the UK. Mr. G. Matthews, the Pharmaceutical Assessor of the Medicines and Health Care Products Regulatory Agency, in a letter sent to BTA dated 19 October 2005, has clarified that “The regulations on medicine allow doctors to prescribe an unlicensed medicine for a patient to meet such a special clinical need, on their own direct personal responsibility. Where these unlicensed medicines are not available in the UK they can be imported by appropriately licensed medicines wholesalers, for supply to a doctor or pharmacy, to meet these needs.”

The MHRA does allow doctors to prescribe Armour Thyroid from Forest Pharmaceutical.104 Armour is a fully official FDA-registered drug in the USA, and appears in the Martindale Pharmacopoeia page 1604.105 It is legal to prescribe Armour Thyroid to a patient in the UK and it can be delivered by UK pharmacies if there is a prescription from a licensed physician. Indeed, Armour Thyroid can be obtained very simply on a named patient basis and Idis World Medicines will source this.106

Armour and several other thyroid medications were ‘grandfathered’ in when Congress passed the Kefauver-Harris Drug Efficacy Amendments of 1962 to tighten control over drugs.107, 108 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.107, 108 Too much evidence to the contrary developed concerning the levothyroxine products and the FDA decided none was generally recognised as safe and effective, so these 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.

BTA Statement:

F. The cost of Armour Thyroid may be up to 20 per month, compared to an equivalent cost of 1 per month for thyroxine. Furthermore, Armour Thyroid is not eligible to be claimed on the prescription exemption certificate (FP10).

The 20 quoted by BTA is unhelpful, since it is unrelated to dosage. Generic synthetic thyroxine may be of most variable potency, manufacturer to manufacturer. Thyroid experts are convinced that the method of determining bio equivalence is flawed, and that there may be important differences among preparations. Casually changing a patient to a new levothyroxine preparation could lead to over- or under-treatment, with possible adverse effects. An extreme case would be a change to a more potent preparation, causing atrial fibrillation and fatal embolism in a susceptible individual.109 Most patients receiving thyroid medication have noticed that the effectiveness of their treatment frequently varies with the manufacturer. The choice of manufacturer by the chemist is not related to quality, but cheapness. The US FDA insists that doctors and pharmacists stay with the manufacturer whose preparation was used initially, since the variations in potency are unacceptable.19, 20, 21, 22, 23, 24, 25, 26, 32, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 89

Simon Stephenson (2007), Head of Medicines, Pharmacy & Industry Business Unit, Department of Health (July 2007) sent TPA-UK a breakdown of the actual cost of the different dose tablets of Armour. The average cost per unit of the differing strengths of Armour Thyroid dispensed in primary care over the course of the year April 2006 to March 2007 is outlined in the table below. A pharmacist stated the average cost of all prescriptions per patient, per calendar month is 20.00. The cost of Armour (apart from the 240mg tablet), is far below this.

Strength Est. unit cost in pence: Est. cost for one month supply

Armour Thyroid 240mg 79 22.12

Armour Thyroid 180mg 46 12.88

Armour Thyroid 120mg 43 12.04

Armour Thyroid 90mg 34 9.52

Armour Thyroid 60mg 31 8.68

Armour Thyroid 30mg 27 7.56

Armour Thyroid 15mg 19 5.32

NB. Levothyroxine sodium 150 mcgs costs 1.52 per 28 days supply and is equivalent to about 120mg Armour Thyroid costing 12.04 per calendar month.

The statement from the BTA that Armour is not eligible to be claimed on the prescription exemption certificate (FP10) is false. The NHS Business Services Authority (Prescription Pricing Division) states that: “Myxoedema (underactive thyroid) or other conditions where supplemental thyroid hormone is necessary qualifies for an exemption certificate”. A Medical Exemption Certificate means all prescriptions are free, whatever condition the medication is for.110 Many members of Thyroid Patient Advocacy-UK are prescribed Armour by their doctors using an NHS prescription. As Primary Care Trusts are responsible for funding unlicensed drugs, doctors should first seek their permission.

Potential for significant savings in NHS expenditure

Whilst considering the costs of medication for hypothyroidism, we must consider the cost to the NHS of other medicines prescribed because the T4-only monotherapy does not fully resolve the patients symptoms. Hypothyroid patients chronically used more prescription drugs, especially for diabetes, cardiovascular disease and gastrointestinal conditions.14 These are of great financial burden to the NHS and an overwhelming burden to the quality of life of the tens of thousands of hypothyroid sufferers in the UK alone.

Irving Kirschs recent Department of Psychology at the University of Hull study (25 February 2008) is 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.147

Depression has an association with lower thyroid hormone levels111, 112, 113, 114, 115, 116, 117, 118, 121, 19, 120 and research has shown that improvement can be achieved with thyroid hormone replacement.117, 121, 122, 123, 124, 125, 126, 127

There is an association with anxiety and lower thyroid hormone levels128, 129, 130, 131, 132, 133 and again, research has shown improvement with thyroid treatment replacement therapy.134, 135

Memory loss and Alzheimers disease likewise have an association with lower thyroid hormone levels.136, 37, 138, 139, 140, 141, 142 Both these conditions have shown improvement with thyroid treatment.143, 144, 145, 146

TPA-UK takes the view that all doctors should have freedom of choice in prescribing T4 alone, combined synthetic T4/T3, T3 alone or Armour Thyroid. The selection of treatment,
whether synthetic or natural, should be a matter between the patient and the doctor, both having freedom of choice in this respect. Medical practitioners should abandon the misconceptions that thyroid extract is inconsistent, dangerous, unreliable and/or outdated, and recognise that Armour Thyroid meets the stringent guidelines laid down by the United States Pharmacopoeia (USP) and the FDA.

In addition, medical practitioners should be strongly encouraged to make a full assessment of the clinical presentation of patients already using Armour Thyroid.

To quote one patient: “I have just tried Armour for a few weeks after being unsuccessfully treated with thyroxine for 2 1/2 years. Unfortunately I ran out of Armour, but for those few weeks my symptoms went, for the first time in years (and Im only 20 so that’s a large proportion of my life). No more muscle aches, joint pain, foggy non-thinking brain, tiredness, depression. Then when I ran out, I started thyroxine again. Now the dreaded symptoms have all come back. I now know how needed Armour is, and think it is verging on negligent that it can’t be prescribed to me.”148

TPA-UK has demonstrated the safety and efficacy of Armour Thyroid and its benefits for many patients. In thyroid medicines as with most things, one size does not fit all!


1. The Association of Clinical Biochemists, The British Thyroid Association, The British Thyroid Foundation. “UK Guidelines for the Use of Thyroid Function Tests”. July 2006.

2. Gull WW. “On a cretinoid state supervening in adult life in women.” Trans Clin Soc Lond, 1874; 7:180-185.

3. Murray GR. “Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep”. British Medical Journal, 1891; 2:796-797.

4. Fox EL. “A case of myxoedema treated by taking extract of thyroid by the mouth.” BMJ, 1892; 2:941.

5. MacKenzie HW. “A case of myxoedema treated with great benefit by feeding with fresh thyroid glands.” British Medical Association, 18912; 2:940.

6. Baumann E. “Ueber das normale Vorkommen von Jod im Thierkrper.” Hoppe-Seylers Z Physid Chem, 1895; 21:319-330.

7. Kendall EC. “The isolation in crystalline form of the compound which occurs in the thyroid: its chemical nature and physiologic activity”. Journal of The American Medical Association, 1915; 64:2042-2043.

8. Harington CR and Barger G. “Thyroxine III. Constitution and synthesis of thyroixine.” Bio Chem J, 1927; 21:169-183.

9. Abraham GE. “The Wolff-Chaikoff effect: Crying wolf?” The Original Internist, 2005; 12(3):112-118.

10. Abraham GE. “The History of Iodine in Medicine Part lll: Thyroid Fixation and Medical Iodophobia” June 2006. The Original Internist, 13:71-78

11. Astwood EB et al. Goodman and Gilman’s the Pharmacological Basis of Therapeutics, fourth ed. New York: The Macmillan Company; 1970.

12. Derry DM. Breast Cancer and Iodine. Trafford Publ., Canada, 2001; 39.

13. Abraham GE. “The safe and effective implementation of orthoiodosupplementation in medical practice.” The Original Internist, 2004; 11(1):17-36.

14. Lowe, John. “Thyroid Hormone Replacement Therapies: Ineffective and Harmful for Many Hypothyroid Patients.” May 4, 2004

15. 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

16. Rees-Jones RW, Larsen PR. Triiodothyronine and thyroxine content of desiccated thyroid tablets”. Metabolism. 1977 Nov;26(11):1213-8

17. Rees-Jones RW, Rolla AR, Larsen PR. “Hormonal content of thyroid replacement preparations”. JAMA. 1980 Feb 8;243(6):549-50.

18. LeBoff MS, Kaplan MM, Silva JE, Larsen PR. “Bioavailability of thyroid hormones from oral replacement preparations”. Metabolism. 1982 Sep;31(9):900-5.

19. Gaby AR.”Sub-laboratory hypothyroidism and the empirical use of Armour thyroid”. Altern Med Rev. 2004 Jun;9(2):157-79

20. 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

21. Alan R. Gaby, MD “Alternative Medicine Review” Volume 9, Number 2, 2004

22. Armour Thyroid (thyroid tablets USP).

23. Mary Shomon: “Armour Thyroid and Thyrolar; Alternatives to Synthroid and the Other TG4-Only Drugs. December 26th. 2003.

24. Gail Valentine. “The Advantages of whole thyroid; Slowing Age-related Decline, Life Enhancement.

25. Arem, R., The Thyroid Solution, Ballantine Books, 1999, New York.

26. Shames, RL, Shames, KH, Thyroid Power: 10 Steps to Total Health, Harper Collins Publishers, New York, 2001.

27. Saravanan, P., et al, Clinical Endocrinology 57 (5), 577-585, 2002.

28. Rothfeld, G.S., Romaine, D.S., “Thyroid Balance: Traditional and Alternative Methods for Treating Thyroid Disorders”, Adams Media Corporation, Avon, Massachusetts, USA, 2003.

29. Nicoloff JT, Spencer CA. “The use and misuse of the sensitive thyrotropin assay”. J Clin Endocrinol Metab. 1990;71:553-8.

30. De Los Santos ET, Mazzaferri EL. “Sensitive thyroid-stimulating hormone assays”: Clinical applications and limitations. Compr Ther. 1988; 14(9): 26-33.

31. Becker DV, Bigos ST, Gaitan E, Morris JCrd, rallison ML, Spencer CA, Sugarawa M, Van Middlesworth L, Wartofsky L. “Optimal use of blood tests for assessment of thyroid function”. JAMA 1993 Jun 2; 269: 273 (“the decision to initiate therapy should be based on both clinical and laboratory findings and not solely on the results of a single laboratory test”)

32. Rippere V. Biochemical victims: “False negative diagnosis through overreliance on laboratory resultsa personal report”. Med Hypotheses. 1983; 10(2): 113

33. Gautam Das, Shweta Anand & Parijat De. Diabetes & Endocrine Unit, City Hospital, Birmingham, United Kingdom Endocrine Abstracts (2007)13 P316

34. Food and Drug Administration, Department of Health and Human Services “Recalls and Field Corrections. Armour Thyroid” 11th May 2005.

35. Hubbard WK. “FDA notice regarding levothyroxine sodium”. Federal Register. 1997; 62(157): 1-1

36. 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

37. Rita Chappelle. “FDA Acts to Ensure Thyroid Drugs Dont Lose Potency Before Expiration Date” October 2007.Food and Drugs Administration News.

38. Pearch, C.J. and Himsworth, R.L. “Total and free thyroid hormone concentration in patients receiving maintenance replacement treatment with thyroxine”. Brit. Med. J., 288: 693-695, 1984.

39. Chopra IJ, Carlson HE, Solomon DH.” Comparison of inhibitory effects of 3,5,3′-triiodothyronine (T3), thyroxine (T4), 3,3,’,5′-triiodothyronine (rT3), and 3,3′-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thyrotropin in the rat in vitro”. Endocrinology. 1978 Aug;103(2):393-402.

40. Lewis M, Yeo PP, Green E, Evered DC. “Inhibition of thyrotrophin-releasing hormone responsiveness by physiological concentrations of thyroid hormones in the cultured rat pituitary gland”. J. Endocrinol. 1977 Sep;74(3):405-14.

41. Wenzel KW, Meinhold H, Schleusener H. “T3 is more potent to inhibit TSH secretion than T4. Different effects of oral doses of triiodothyronine or thyroxine on the inhibition of thyrotrophin releasing hormone (TRH) mediated thyrotrophin (TSH) response in man”. Acta Endocrinol. 1975 Sep;80(1):42-8.

42. Sawin CT, Hershman JM, Chopra IJ. “The comparative effect of T4 and T3 on the TSH response to TRH in young adult men”. J. Clin. Endocrinol. Metab. 1977 Feb;44(2):273-8.

43. Maeda M, Kuzuya N, Masuyama Y, Imai Y, Ikeda H. “Changes in serum triiodothyronine, thyroxine, and thyrotropin during treatment with thyroxine in severe primary hypothyroidism”. 1976 Jul; J Clin Endocrinol Metab. 43(1):10-7.

44. Saravanan P, Simmons DJ, Greenwood R, Peters TJ, Dayan CM. “Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial”. Clin Endocrinol Metab. 2005 Feb;90(2):805-12

45. Kloppenburg M, Dijkmans BA, Rasker JJ. “Effect of therapy for thyroid dysfunction on musculoskeletal symptoms”. Clin Rheumatol. 1993 Sep;12(3):341-5

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

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

48. Arlot S, Debussche X, Lalau JD, Mesmacque A, Tolani M, Quichaud J, Fournier A. “Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment”. Intensive Care Med. 1991;17(1):16-8

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

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

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

52. 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

53. 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

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

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

56. 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

57. 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

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

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

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

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

62. 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

63. Asper SP Jr, Selenkow HA, and Plamondon CA. “A comparison of the metabolic activities of 3,5,3-triiodothyronine and l-thyroxine in myxedema”. Bull Johns Hopkins Hosp. 1953; 93: 164

64. 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):819-2

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

66. 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

67. 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

68. Paier B, Hagmller K, Nolli Mi, Gonzalez Pondal M, Stiegler C and Zaninovich AA. “Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver” J Endocrinol. 1993; 138: 219-24

69. Barregrd L, Lindstedt G, Schtz A, Sllsten G. “Endocrine function in mercury exposed chloralkali workers”. Occup Envir Med. 1994; 51: 536-40

70. 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

71. 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

72. 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

73. 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

74. 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

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

76. 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

77. 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

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

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

80. 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

81. 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

82. 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

83. 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

84. 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

85. 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

86. 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

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

88. 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

89. 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.

90. Loeser A. “Thyroid and ovary”. Journal of the American Medical Association 1935;104: 870.

91. Morse M. “The effective principle in thyroid accelerating involution in frog larvae”. J Biol Chem 1914;19:421-429

92. 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

93. Brownstein, D., Overcoming Thyroid Disorders, Medical Alternatives Press, 2002.

94. Lombardi, A.Lanni, A.Silvestri,E. de Lange, P.Goglia, F.Moreno,M. 3, 5Diiodothyronine: Biological Actions and Therapeutic Perspectives. pp.255-265 (11)

95. Lanni A”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.

96. Goglia et al. FEBS Letters. 452, 115-120 (1999)

97. Lombardi et al. Biochem J. 330, 521-526 (1998).

98. Lombardi et al. Endocrinology. 141, 1729-1734 (2000)

99. Ball et al. J Molec Endocrinology. 19, 137-147 (1997).

100. 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

101. J. Kvetny. Horm. Metab. Res. 24:322-325, 1992.

102. 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.

103. 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):291-7

104. Matthews,G. “Armour Thyroid and Porcine Thyroid Extract Replacement Therapy”. . June 29.2004.Medicines and Healthcare Products Regulatory Agency MHRA letter

105. Martindale’s. Pharmacology and Toxicology Center. Prescription & Over-the-Counter Drug Databases:

106. IDIS Ltd. Sourcing Unlicensed Named Patients Medicines. .

107. Krantz JC Jr., “New Drugs and the Kefauver-Harris Amendment”, J New Drugs, 1966, Mar-Apr;6(22):77-9

108. Krantz JC Jr., “The Kefauver-Harris amendment after sixteen years,” Mil Med. 1978 Dec;143(12):883.

109. Green. William L. “New Questions Regarding Bioequivalence of Levothyroxine Preparations: A Clinicians Respones”. The AAPS Journal 2005; 7 (1) Article 7

110. NHS Prescription Pricing Division. “Medical Exemption Certificate (MEDIX)”

111. Pop VJ, Maartens LH, Leusink G, van Son MJ, Knottnerus AA, Ward AM, Metcalfe R, Weetman AP. “Are autoimmune thyroid dysfunction and depression related? ” J Clin Endocrinol Metab. 1998 Sep;83(9):3194-7

112. Haggerty JJ Jr, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ Jr. “Subclinical hypothyroidism: a modifiable risk factor for depression? ” Am J Psychiatry. 1993 Mar;150(3):508-10

113. Gold MS, Pottash AL, Extein I. “Symptomless autoimmune thyroiditis in depression.” Psychiatry Res. 1982 Jun;6(3):261-9

114. O’Shanick GJ, Ellinwood EH Jr. “Persistent elevation of thyroid-stimulating hormone in women with bipolar affective disorder. ” Am J Psychiatry. 1982 Apr;139(4):513-4

115. Howland RH. “Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment.” J Clin Psychiatry. 1993 Feb;54(2):47-54

116. Kirkegaard C, Norlem N, Lauridsen UB, Bjorum N, Christiansen C. “Protirelin stimulation test and thyroid function during treatment of depression.” Arch Gen Psychiatry. 1975 Sep;32(9):1115-8

117. Bauer MS, Whybrow PC, Winokur A. “Rapid cycling bipolar affective disorder. I. Association with grade I hypothyroidism.” Arch Gen Psychiatry. 1990 May;47(5):427-32

118. Haggerty JJ Jr, Evans DL, Golden RN, Pedersen CA, Simon JS, Nemeroff CB. “The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders.” Biol Psychiatry. 1990 Jan 1;27(1):51-60

119. Cole DP, Thase ME, Mallinger AG, Soares JC, Luther JF, Kupfer DJ, Frank E. “Slower treatment response in bipolar depression predicted by lower pre-treatment thyroid function.” Am J Psychiatry. 2002 Jan;159(1):116-21

120. Joffe RT, Marriott M. “Thyroid hormone levels and recurrence of major depression.” Am J Psychiatry. 2000 Oct;157(10):1689-91 (“the time to recurrence of major depression was inversely related to T3 levels but not to T4 levels”)

121. Afflelou S, Auriacombe M, Cazenave M, Chartres JP, Tignol J. “Administration of high dose levothyroxine in treatment of rapid cycling bipolar disorders. Review of the literature and initial therapeutic application apropos of 6 cases.” Encephale. 1997 May-Jun;23(3):209-17

122. Bauer M, Baur H, Berghofer A, Strohle A, Hellweg R, Muller-Oerlinghausen B, Baumgartner A. “Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders.” J Affect Disord. 2002 Apr;68(2-3):285-94

123. Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M. “Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine.” Am J Psychiatry. 1984 Dec;141(12):1614-6

124. Prange AJ Jr. “Novel uses of thyroid hormones in patients with affective disorders.” Thyroid. 1996 Oct;6(5):537-43

125. Birkenhager TK, Vegt M, Nolen WA. “An open study of triiodothyronine augmentation of tricyclic antidepressants in inpatients with refractory depression.” Pharmacopsychiatry. 1997 Jan;30(1):23-6

126. Joffe RT, Singer W, Levitt AJ, MacDonald C. “A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression.” Arch Gen Psychiatry. 1993 May;50(5):387-93

127. Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP, Leight KL, Whybrow PC. “Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature.” Am J Psychiatry. 2001 Oct;158(10):1617-22

128. Kikuchi M, Komuro R, Oka H, Kidani T, Hanaoka A, Koshino Y. “Relationship between anxiety and thyroid function in patients with panic disorder.” Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):77-81

129. Bauer M, Priebe S, Kurten I, Graf KJ, Baumgartner A. “Psychological and endocrine abnormalities in refugees from East Germany: Part I. Prolonged stress, psychopathology, and hypothalamic-pituitary-thyroid axis activity.” Psychiatry Res. 1994 Jan;51(1):61-73

130. Magliozzi JR, Maddock RJ, Gold AS, Gietzen DW. “Relationships between thyroid indices and symptoms of anxiety in depressed outpatients.” Ann Clin Psychiatry. 1993 Jun;5(2):111-6

131. Sait Gonen M, Kisakol G, Savas Cilli A, Dikbas O, Gungor K, Inal A, Kaya A. “Assessment of anxiety in subclinical thyroid disorders.” Endocr J. 2004 Jun;51(3):311-5

132. Larisch R, Kley K, Nikolaus S, Sitte W, Franz M, Hautzel H, Tress W, Muller HW. “Depression and anxiety in different thyroid function states.” Horm Metab Res. 2004 Sep;36(9):650-3

133. Constant EL, Adam S, Seron X, Bruyer R, Seghers A, Daumerie C. “Anxiety and depression, attention, and executive functions in hypothyroidism.” J Int Neuropsychol Soc. 2005 Sep;11(5):535-44

134. Landen M, Baghaei F, Rosmond R, Holm G, Bjorntorp P, Eriksson E. “Dyslipidemia and high waist-hip ratio in women with self-reported social anxiety.” Psychoneuroendocrinology. 2004 Sep;29(8):1037-46 (Serum levels of free thyroxin (14+/-2 vs. 16+/-4, P=0.04) were lower in subjects confirming social anxiety)

135. Venero C, Guadano-Ferraz A, Herrero AI, Nordstrom K, Manzano J, de Escobar GM, Bernal J, Vennstrom B. “Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor,” 2005.

136. Nakanishi T. “Consideration on serum triiodothyronine (T3), thyroxine (T4) concentration and T3/T4 ratio in the patients of senile dementia – is it possible to prevent cerebro-vascular dementia?” Igaku Kenkyu. 1990 Feb;60(1):18-25

137. Ichibangase A, Nishikawa M, Iwasaka T, Kobayashi T, Inada M. “Relation between thyroid and cardiac functions and the geriatric rating scale.” Acta Neurol Scand. 1990 Jun;81(6):491-8

138. Molchan SE, Lawlor BA, Hill JL, Mellow AM, Davis CL, Martinez R, Sunderland T. “The TRH stimulation test in Alzheimer’s disease and major depression: relationship to clinical and CSF measures.” Biol Psychiatry. 1991 Sep 15;30(6):567-76

139. Burmeister LA, Ganguli M, Dodge HH, Toczek T, DeKosky ST, Nebes RD. “Hypothyroidism and cognition: preliminary evidence for a specific defect in memory.” Thyroid. 2001 Dec;11(12):1177-85

140. Monzani F, Pruneti CA, De Negri F, Simoncini M, Neri S, Di Bello V, Baracchini Muratorio G, Baschieri L. “Preclinical hypothyroidism: early involvement of memory function, behavioral responsiveness and myocardial contractility.” Minerva Endocrinol. 1991 Jul-Sep;16(3):113-8

141. Baldini IM, Vita A, Maura MC, Amodei V, Carrisi M, Bravin S, Cantalamessa L. “Psychopathological and cognitive features in subclinical hypothyroidism.” Prog Neuropsychopharmacol Biol Psychiatry. 1997 Aug;21(6):925-35

142. Ganguli M, Burmeister LA, Seaberg EC, Belle S, DeKosky ST. “Association between dementia and elevated TSH: a community-based study. ” Biol Psychiatry. 1996 Oct 15;40(8):714-25

143. Monzon Monguilod MJ, Perez Lopez-Fraile I. “Subclinical hypothyroidism as a cause of reversible cognitive deterioration.” Neurologia. 1996 Nov;11(9):353-6

144. Kinuya S, Michigishi T, Tonami N, Aburano T, Tsuji S, Hashimoto T. “Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism.” Clin Nucl Med. 1999 Sep;24(9):666-8

145. Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, Baschieri L. “Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment.” Clin Investig. 1993 May;71(5):367-71

146. Medline Plus. The MedMaster Patient Drug Information database. “Liothyronine”:

147. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. “Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration.” 2008, PLoS Med 5(2): e45 doi:10.1371/journal.pmed.0050045: Access full article at

148. International Patients Petition for Better Diagnosis and Treatment Choice for Hypothyroid Patients.

The British Thyroid Association Reference.

1. An FDA enforcement removed more than half a million bottles of Armour Thyroid from US pharmacies in 2005 due to unstable concentrations of thyroid hormone in the preparation. [