Desiccated thyroid extract
Desiccated thyroid or thyroid extract, refers to porcine (or mixed beef and pork) thyroid glands, dried and powdered for therapeutic use. Pork, or mixed beef and pork, thyroid preparations were developed in the late 1800s, and are still used today to treat hypothyroidism (underactive thyroid gland). This product is sometimes referred to as "natural thyroid", "natural thyroid hormones", "pork thyroid", thyroid USP, thyroid BP, or by the name of the best-known brand, "Armour thyroid".
Desiccated thyroid has been described in the United States Pharmacopoeia for nearly a century as: the cleaned, dried, and powdered thyroid gland previously deprived of connective tissue and fat... obtained from domesticated animals that are used for food by man (USP XVI). In the last few decades, pork alone is the usual source. Typically the potency has been specified only by iodine content ("not less than 0.17% and not more than 0.23%") rather than hormonal content or activity. The specifications of the British Pharmacopoeia (BP) are similar.
The best known American brand is Armour®. Others include Forest Labs' Naturethroid, Westhroid by Western Research Labs/Time Caps, and Qualitest by Time Caps Labs. Canada's desiccated thyroid is made by Erfa and called simply Thyroid. All consist of desiccated porcine thyroid powder, differing only in the binders and fillers.
All brands contain a mixture of thyroid hormones: T4 (thyroxine), T3 (triiodothyronine) in the proportions usually present in pig thyroids (approximately 80% T4 and 20% T3). Armour is made in the following strengths: 1/8, 1/4, 1/2, 1, 2, and 3 grain as well as 4 and 5 grain tablets. One grain (about 60 mg) of desiccated thyroid contains about 38 mcg of T4 and 9 mcg of T3. Because the preparation is whole thyroid gland, each 60 mg tablet also contains over 59 mg of all of the other constituents of pork thyroid glands.
The earliest oral treatment for hypothyroidism consisted of thyroid extract. George Redmayne Murray of the United Kingdom first described treatment of myxedema with thyroid extract in 1891, and published a description of long-term successful treatment (28 years) of a patient with myxedema (severe hypothyroidism) in 1920 His treatment was quickly adopted in North America and Europe. The first recorded American use dates to 1891 by a woman who was still taking it 52 years later at 84 years of age 
Desiccated thyroid extract was prepared inexpensively from pig and cow thyroid glands. The glands were dried (desiccated), ground to powder, combined with binder chemicals, and pressed into pills. This was a new use for parts that were previously unwanted slaughterhouse offal, and Armour and Company, the dominant American meatpacker in the 20th century, supplied the best-known brand of thyroid extract.
Replacement by thyroid extract in hypothyroidism was one of the most effective treatments of any disease available to physicians before the middle of the twentieth century, and in severe cases afforded dramatic relief of the myriad symptoms. The decision to treat was usually based on the presence of signs and symptoms of hypothyroidism because there were no accurate, readily available laboratory tests of thyroid function. Many less severe cases of hypothyroidism went untreated and many adults with fatigue or adiposity due to other causes were treated, with primarily placebo benefits. Dosage was regulated by improvement of symptoms.
In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by synthetic levothyroxine (T4), or by combinations of synthetic T4 and T3. Replacement occurred faster in the United Kingdom than in North America, but by the 1980s more patients were being prescribed synthetic levothyroxine or T4/T3 combinations than desiccated thyroid extract.
If desiccated thyroid was an effective treatment for most people why did the change occur? A combination of factors can be identified: a desire for improved effectiveness, medical evidence, scientific theory, cultural fashion, and effective marketing.
- Although thyroid extract was useful and usually effective, some patients continued to complain of fatigue, weight gain, or other symptoms. Dosing until the 1960s was often a matter of prolonged adjustment trials. 
- It was known that not all of the iodine content of thyroid extract was in the form of effective T4 and T3 and that actual content of available preparations varied more than the permitted 15%.    It was hoped that better dosing precision with synthetic thyroxine would increase the proportion of patients effectively treated. In 1980, a widely publicized investigation published in JAMA revealed continued large ranges of hormone content and potency in all of the available thyroid extracts on the American market .
- By the 1960s, it was known that thyroxine was the essential hormone produced by the thyroid gland, and that most T3 was manufactured in other parts of the body by deiodination of thyroxine. It was demonstrated in hypothyroid animals and people that replacement of thyroxine alone corrected the measurable manifestations of hypothyroidism . By the 1970s doctors could measure T4, T3, and TSH in human blood with approximate accuracy and confirmed that treatment with thyroxine alone could produce normal blood levels of both T4 and T3. In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism.
- It was discovered that a healthy person varied the amount of T3 produced from T4 in response to changing needs and conditions and it seemed wiser not to bypass this control system by providing larger amounts of T3 than were naturally produced each day.
- Furthermore, when T3 could be measured, it was discovered that thyroid extract and synthetic combinations of T4 and T3 produced significantly greater fluctuations of T3 throughout the day than occurred in healthy people or hypothyroid people treated with thyroxine alone.
- Endocrinologists, the doctors with the most knowledge about thyroid disorders, and who treated the most thyroid patients, found that treatment with thyroxine alone worked as well or better than thyroid extract for the majority of patients, although even thyroxine did not reverse all the symptoms of a minority.
- Cultural fashion and marketing played a role. In the middle of the 20th century the pharmaceutical chemistry had been discovering the active molecules in a variety of plant and animal remedies from aspirin to digitoxin to vitamins, and producing them synthetically, with improvements in purity and control of dosage. In that cultural context it was easy to market thyroxine as superior to dried animal glands.
- Synthroid, one of the most successful brand names in pharmaceutical marketing history became as synonymous with thyroid replacement to generations of American primary care doctors as Kleenex or Xerox became with their respective products.
Thyroid care changed in other ways as well. Accurate T4 and T3 measurements became widely used in the 1970s, and by the late 1980s, TSH measurement had become sensitive enough to detect mild degrees of hyperthyroidism and overtreatment. To no one's surprise, blood levels of thyroid hormones and TSH were found to be the best predictors of objective benefits from thyroid replacement: those with the most severe measurable deficiency enjoyed the most dramatic and sustained benefits. It was also discovered that even mild hyperthyroidism as defined by a suppressed TSH level, whether due to disease or overtreatment, was associated with poorer bone density in women, and with higher rates of atrial fibrillation in elderly patients. Endocrinologists and most other doctors began to trust the TSH more and more as an index of optimal replacement dose.
As more doctors prescribed thyroxine instead of thyroid extract, the use and especially a publicized preference for thyroid extract became more associated with those whose medical practices deviated in many ways from standard care. (See complementary and alternative medicine.) This association became a disincentive for using thyroid extract to those not wishing to be considered unscientific or irrational.
A resurgence of popularity of thyroid extract and ongoing controversy
Nevertheless, desiccated thyroid pills have continued to be preferred by a minority of patients and doctors who claim better relief of subjective symptoms such as fatigue and depressed mood. Many proponents of desiccated thyroid feel passionately about the issue, and feel that thyroid extract should again become the standard treatment offered to all patients. A number of books and websites promote desiccated thyroid use and condemn the reluctance of most endocrinologists to endorse their preference.
A number of specific claims are commonly made about thyroid extract:
- Thyroid extract is better than thyroxine because it contains both T4 and T3, and both are made by a healthy thyroid gland.
- Some brands (especially Armour) are more effective than others.
- Doses should be increased until symptoms are relieved regardless of laboratory tests.
- Thyroid extract may be more effective if divided into three doses a day to reduce fluctuations of T3 levels..
- Thyroid extract may be more effective if allowed to dissolve under the tongue instead of swallowed.
- Other constituents of the dried thyroid glands besides the T4 and T3 (e.g., unmeasured amounts of diiodothyronine (T2), monoiodothyronine (T1), calcitonin, other protein-bound iodine) may contribute to its effectiveness or confer additional benefits.
- A product produced by farm, slaughterhouse, and factory is "natural", and therefore preferable to thyroxine molecules synthesized in a factory alone.
To endocrinologists the preference of some hypothyroid people for thyroid extract raises some important questions which current evidence cannot answer with certainty:
- Is the reason some people fail to have complete relief of symptoms when tests show normal levels simply because there are other causes of fatigue, depression, and weight gain and these people are mistakenly attributing the problems to the thyroid and simply enjoying a placebo effect if they claim better relief from thyroid extract?
- Does a combination of T4 and T3 provide more effective symptom relief for some people than T4 alone? Multiple controlled trials have shown inconsistent benefits of various ratios of T4 and T3.  Even if most people with hypothyroidism enjoy complete relief of symptoms with thyroxine alone, are there people who need T3 as well because they cannot generate normal amounts from T4 as most people do?
- Is the perceived benefit simply a result of overtreatment, such that the same relief could be achieved by pushing a thyroxine dose to higher levels?
- Is the TSH measurement, and its associated 'normal' range, the best indicator of optimal replacement dose? Most research evidence suggests it is, but some patients feel better at doses which produce abnormally high blood levels of T4 and T3 and suppressed TSH. Is this simply a stimulant effect of high doses, similar to caffeine or amphetamine? How high is the risk of prolonged overtreatment to the bones, heart, and other parts of the body, and is it worth an improvement in subjective well-being?
Despite claims of proponents that desiccated thyroid pills are superior to thyroxine or combinations of T4 and T3 for most people with hypothyroidism, no controlled clinical trials have been published, and many physicians remain unconvinced that the superiority is anything other than a placebo effect or an overtreatment effect.
Current status of thyroid extract use
At present, a large majority of people (at least in the English-speaking world) of all ages with hypothyroidism are being replaced with synthetic levothyroxine. When their blood levels of thyroid hormones and TSH are most normal, the majority have no more signs or symptoms of hypothyroidism than similar members of the population.
A significant minority of adult patients feel that current methods of replacement with thyroxine, guided by normalization of TSH, do not completely eradicate all of the symptoms they attribute to their hypothyroidism. Many of them report that thyroid extract gives them better symptom relief, often at doses that produce abnormal levels of TSH.
Several books promoting natural thyroid hormone replacement are available:
- Dr. David Brownstein. Overcoming Thyroid Disorders. Medical Alternatives Press, 2002. ISBN 0-9660882-2-0.
- Barry Durrant-Peatfield, MBBS, LRCP, MRCS. The Great Thyroid Scandal and How To Survive It. Barons Down Publishing, 2002. ISBN 0-9544203-0-6.
- Steven F. Hotze, MD. Hormones, Health, and Happiness. Forrest Publishing, 2005. ISBN 0-9765751-0-8.
- Mary Shomon. Living Well With Hypothyroidism: What Your Doctor Doesn't Tell You...That You Need to Know. HarperCollins, 2005. ISBN 0-0607409-5-7.
- Mark Starr, MD. Hypothyroidism, the Epidemic. New Voice. ISBN 0-9752624-0-8.
- ^ Murray GR. The life history of the first case of myxoedema treated by thyroid extract. Br Med J 1920;i:359-60.
- ^ Burgess AM. Myxedema-- controlled by thyroid extract for fifty-two years: report of a case. Ann Internal Med 1946; 25:146.
- ^ Means JH, DeGroot LJ, Stanbury JB. The Thyroid and its Diseases. 3rd ed. New York:McGraw Hill, 1963. See chapter 9 for a lengthy discussion of the difficulties of assessing treatment in the era before effective tests, as well as the doctors' impressions of the superiority of the new synthetic thyroxine that had just become available.
- ^ Macgregor AG. Why does anybody use thyroid B.P.? Lancet 1961; 1:329
- ^ Catz B, Ginsburg E, Salenger S. Clinically inactive thyroid U.S.P.: a preliminary report. New Engl J Med 1962; 266:136.
- ^ Pileggi VJ, Golub DJ, Lee ND. Determination of thyroxine and triiodothyronine in commercial preparations of desiccated thyroid and thyroid extract. J Clin Endocrinol Metab 1965; 25:949-56.
- ^ Mangieri CN, Lund MH. Potency of United States pharmacopoiea desiccated thyroid tablets as determined by the antigoitrogenic assay in rats. J Clin Endocrinol Metab 1970; 30:102-4.
- ^ Rees-Jones RW, Rolla AR, Larsen PR. Hormonal content of thyroid replacement preparations. JAMA 1980; 243:549.
- ^ Braverman LE, Ingbar SH, Sterling K. Conversion of thyroxine to triiodothyronine in athyreotic human subjects. J Clin Invest 1970; 49:855-64.
- ^ Saberi M, Utiger RD. Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy. J Clin Endocrinol Metab 1974; 39:923-7.
- ^ Capiferri R, Evered D. Investigation and treatment of hypothyroidism. Clin Endocrinol Metab (1979) 8:39-48.
- ^ Surks MI, Schadlow AR, Oppenheimer JH. A new radioimmunoassay for L-triiodothyronine: measurement in thyroid disease and in patients maintained on hormonal replacement. J Clin Invest 1972; 51:3104-13.
- ^ Capiferri R, Evered D. Investigation and treatment of hypothyroidism. Clin Endocrinol Metab (1979) 8:39-48.
- ^ Shomon, Mary. Living Well With Hypothyroidism: What Your Doctor Doesn't Tell You...That You Need to Know (2005).
- ^ [http://health.groups.yahoo.com/group/NaturalThyroidHormones Yahoo Groups] Natural Thyroid Hormones group
- ^ [http://www.stopthethyroidmadness.com/mistakes-patients-make/ Stop the Thyroid Madness] Mistakes Patients Make
- ^ [http://health.groups.yahoo.com/group/thyroid/?yguid=6933490 Yahoo Groups] - Open Forum to Discuss Thyroid Disease
- ^ [http://www.stopthethyroidmadness.com/sublingual Sublingual use].
- ^ Clyde PW, Harari AE, Getka EJ, Shakir KM. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 2003;290:2952-8. PMID 14665656.
- ^ Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J. Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med 2005;142:412-24. PMID 15767619.
- ^ [http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf] AACE Thyroid Task Force. American Association of Clnical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. 2002, amended 2006.