Desiccated thyroid extract

The American Association of Clinical Endocrinologists{{cite journal | vauthors = Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA | display-authors = 6 | title = Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association | journal = Thyroid | volume = 22 | issue = 12 | pages = 1200–1235 | date = December 2012 | pmid = 22954017 | doi = 10.1089/thy.2012.0205 | url = https://www.aace.com/files/final-file-hypo-guidelines.pdf | access-date = 8 November 2014 | url-status = dead | archive-url = https://web.archive.org/web/20160114192331/https://www.aace.com/files/final-file-hypo-guidelines.pdf | archive-date = 14 January 2016 }} and the Royal College of Physicians{{cite news |title=Thyroid disorders 'misdiagnosed' |url=http://news.bbc.co.uk/2/hi/health/7965417.stm |newspaper=BBC News |access-date=30 March 2009 |quote=the only accurate way to diagnose a thyroid disorder is via a blood test which measures hormone levels, and the only scientifically proven way of treating the condition is by topping up a patient's natural thyroxine levels with a synthetic form of the hormone. |date=27 March 2009}} recommend against the use of thyroid extract for the treatment of hypothyroidism. Concerns include the potential for adverse effects from superphysiological levels of T3 and the absence of long-term safety data from randomized clinical trials. They recommend levothyroxine as the preferred treatment. Some practitioners refuse to use desiccated thyroid.{{cite web|url=http://www.endocrinetoday.com/comments.aspx?rid=35717 |title=Endocrine Today Blog |publisher=Endocrinetoday.com |access-date=24 July 2014}}

Each 64.8 mg (one grain) of thyroid extract contains approximately 38 μg and 9 μg of measurable levothyroxine (T4) and liothyronine (T3), respectively.

Arguments against desiccated thyroid include:

1. Desiccated thyroid preparations have a greater variability from batch to batch than synthetic ones.
2. Desiccated thyroid has roughly a 4:1 ratio of thyroxine (T4) to triiodothyronine (T3). In humans, the ratio is 11:1.[http://www.endocrinetoday.com/comments.aspx?rid=35766 Repas, Thomas. Desiccated thyroid in the management of hypothyroidism: Part I.]
3. A combination of various ratios of T4 and T3 might not provide benefits over T4 alone. Some controlled trials have shown inconsistent benefits of various ratios of T4 and T3.{{cite journal | vauthors = Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, Segal RL | title = American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism | journal = Endocrine Practice | volume = 8 | issue = 6 | pages = 457–469 | date = 2002 | pmid = 15260011 | doi = 10.4158/1934-2403-8.6.457 | url = https://www.aace.com/files/hypo_hyper.pdf | access-date = 3 February 2015 | url-status = dead | archive-url = https://web.archive.org/web/20151208150759/https://www.aace.com/files/hypo_hyper.pdf | archive-date = 8 December 2015 }}{{cite journal | vauthors = Clyde PW, Harari AE, Getka EJ, Shakir KM | title = Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial | journal = JAMA | volume = 290 | issue = 22 | pages = 2952–2958 | date = December 2003 | pmid = 14665656 | doi = 10.1001/jama.290.22.2952 | doi-access = }}
4. The use of desiccated thyroid is usually accompanied with the practice of dosing according to symptoms instead of dosing to achieve "ideal" lab results (e.g. serum levels of TSH). While there is debate as to what the ideal serum levels are, dosing according to symptoms often results in higher dosages. Most endocrinologists are opposed to these higher dosages as there may be risks of hyperthyroidism and osteoporosis.{{cite web|url=http://www.endocrinetoday.com/comments.aspx?rid=35766 |title=Endocrine Today Blog |publisher=Endocrinetoday.com |access-date=24 July 2014}}
5. The preference for "natural" treatment seems to stem from philosophical belief as opposed to science.{{cite web|url=http://www.endocrinetoday.com/comments.aspx?rid=35803 |title=Endocrine Today Blog |publisher=Endocrinetoday.com |access-date=24 July 2014}}

Arguments for desiccated thyroid include:

1. Desiccated thyroid contains all the hormones produced exclusively by the thyroid gland, including calcitonin. {{citation needed|date=January 2024}}
2. Desiccated thyroid therapy can be combined with synthetic thyroxine (T4) to balance out the T4/T3 correctly.

Desiccated thyroid has been described in the United States Pharmacopoeia for 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).{{Cite book|title = US Pharmacopeia Natural Formulary USP 37 N32 2014 Volume 3 May 1, 2014|publisher = The United States Pharmacopeial Convention|year = 2014|isbn = 9781936424221}} In the last few decades, pork alone is the usual source. Before modern assays, the potency was specified only by iodine content ("not less than 0.17% and not more than 0.23%"), rather than hormonal content or activity.{{Cite book|title = Remington The Science and Practice of Pharmacy | edition = 21st | vauthors = Tory DB |publisher = Lippincott Williams and Wilkins|year = 2006|isbn = 0781763789|location = Philadelphia, PA|pages = 1460, 1461}}

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 1920Murray GR. The life history of the first case of myxoedema treated by thyroid extract. Br Med J 1920;i:359-60. 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 Burgess AM. Myxedema-- controlled by thyroid extract for fifty-two years: report of a case. Ann. Intern. Med. 1946; 25:146.

Desiccated thyroid extract is prepared from pig thyroid glands. The glands are 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. {{Citation needed|date=March 2014}}

Replacement by thyroid extract in hypothyroidism was one of the most effective treatments of any disease available to physicians before the middle of the 20th century, {{Citation needed|date=March 2014}} 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.{{citation needed|date=July 2012}} Dosage was regulated by improvement of symptoms.

Desiccated Thyroid became a commercial treatment option in 1934 with Westhroid,{{citation needed|date=October 2012}}. In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by levothyroxine (synthetic T4), or by combinations of T4 and T3. Replacement occurred faster in the United Kingdom than in North America, but by the 1980s more patients were being prescribed synthetic T4 (levothyroxine) or synthetic T4/T3 combinations than desiccated thyroid extract.{{citation needed|date=December 2013}}

Several reasons have been identified as to why prescriptions changed from desiccated thyroid treatment.

• 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.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.
• 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%.{{cite journal | vauthors = Macgregor AG | title = Why does anybody use thyroid B.P.? | journal = Lancet | volume = 1 | issue = 7172 | pages = 329–332 | date = February 1961 | pmid = 13764789 | doi = 10.1016/s0140-6736(61)91498-2 }}{{cite journal | vauthors = Catz B, Ginsburg E, Salenger S | title = Clinically inactive thyroid U.S.P. A preliminary report | journal = The New England Journal of Medicine | volume = 266 | pages = 136–137 | date = January 1962 | pmid = 13877407 | doi = 10.1056/nejm196201182660308 }}{{cite journal | vauthors = Pileggi VJ, Golub OJ, Lee ND | title = Determination of Thyroxine and Triiodothyronine in Commercial Preparations of Desiccated Thyroid and Thyroid Extract | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 25 | issue = 7 | pages = 949–956 | date = July 1965 | pmid = 14319377 | doi = 10.1210/jcem-25-7-949 }}{{cite journal | vauthors = Mangieri CN, Lund MH | title = Potency of United States Pharmacopeia desiccated thyroid tablets as determined by the antigoitrogenic assay in rats | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 30 | issue = 1 | pages = 102–104 | date = January 1970 | pmid = 5409525 | doi = 10.1210/jcem-30-1-102 | doi-access = free }} It was hoped that better dosing precision with levothyroxine (synthetic) alone 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.{{cite journal | vauthors = Rees-Jones RW, Rolla AR, Larsen PR | title = Hormonal content of thyroid replacement preparations | journal = JAMA | volume = 243 | issue = 6 | pages = 549–550 | date = February 1980 | pmid = 7351788 | doi = 10.1001/jama.1980.03300320041023 }}
• 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 (laboratory test results) of hypothyroidism.{{cite journal | vauthors = Braverman LE, Ingbar SH, Sterling K | title = Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects | journal = The Journal of Clinical Investigation | volume = 49 | issue = 5 | pages = 855–864 | date = May 1970 | pmid = 4986007 | pmc = 535757 | doi = 10.1172/jci106304 | doi-access = free }} 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,{{cite journal | vauthors = Saberi M, Utiger RD | title = Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 39 | issue = 5 | pages = 923–927 | date = November 1974 | pmid = 4422006 | doi = 10.1210/jcem-39-5-923 }} but desiccated thyroid caused supraphysiologic levels of T3.{{cite journal | vauthors = Penny R, Frasier SD | title = Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid | journal = American Journal of Diseases of Children | volume = 134 | issue = 1 | pages = 16–18 | date = January 1980 | pmid = 7350782 | doi = 10.1001/archpedi.1980.02130130008003 }} In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism.{{cite journal | vauthors = Capiferri R, Evered D | title = Investigation and treatment of hypothyroidism | journal = Clinics in Endocrinology and Metabolism | volume = 8 | issue = 1 | pages = 39–48 | date = March 1979 | pmid = 371874 | doi = 10.1016/S0300-595X(79)80008-0 }}
• It was discovered that a healthy person varied the amount of T3 produced from T4 in response to changing needs and conditions{{citation needed|date=October 2012}} and it seemed wiser not to bypass this control system by providing larger amounts of T3 than were naturally produced each day{{Synthesis inline |date=December 2013}}.
• 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.{{cite journal | vauthors = Surks MI, Schadlow AR, Oppenheimer JH | title = A new radioimmunoassay for plasma L-triiodothyronine: measurements in thyroid disease and in patients maintained on hormonal replacement | journal = The Journal of Clinical Investigation | volume = 51 | issue = 12 | pages = 3104–3113 | date = December 1972 | pmid = 4539287 | pmc = 332992 | doi = 10.1172/jci107137 | doi-access = free }}
• Endocrinologists 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.

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.{{Citation needed|date=March 2014}} Blood levels of thyroid hormones and TSH were found to be the best predictors of objective benefits from thyroid replacement{{Synthesis inline |date=December 2013}}: those with the most severe measurable deficiency enjoyed the most dramatic and sustained benefits.{{citation needed|date=December 2013}} 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.{{citation needed|date=December 2013}}

This product is sometimes referred to as thyroid USP, thyroid BP. Brands differing only in binders and fillers.{{Citation needed|date=March 2014}}

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