Desiccated thyroid extract

Desiccated thyroid, also known as thyroid extract, is thyroid gland that has been dried and powdered for medical use.[1] It is used to treat hypothyroidism.[1] It is less preferred than levothyroxine.[1] It is taken by mouth.[1] Maximal effects may take up to 3 weeks to occur.[1]

Desiccated thyroid extract
Combination of
ThyroxineThyroid hormone
TriiodothyronineThyroid hormone
Clinical data
Trade namesArmour Thyroid, NP Thyroid, Nature-Throid
Other namesNatural thyroid, natural thyroid hormones, pork thyroid, thyroid USP, thyroid BP
AHFS/Drugs.comMonograph
License data
Routes of
administration		By mouth
Legal status
Legal status

Side effects may occur from excessive doses.[1] This may include weight loss, fever, headache, anxiety, trouble sleeping, arrythmias, and heart failure.[1] Other side effects may include allergic reactions.[1] Use in pregnancy and breastfeeding is generally safe.[2] Regular blood tests are recommended to verify the appropriateness of the dose.[1] They contain a mixture of thyroxine (T4) and triiodothyronine (T3).[1]

Desiccated thyroid has been used since the late 1800s.[3] It is usually made from pigs, sheep, or cows.[4] It is available as a generic medication.[1] In the United States the wholesale cost for a month of medication is about US$15.30.[5] In 2017, it was the 130th most commonly prescribed medication in the United States, with more than five million prescriptions.[6][7] Usage has decreased since the 1960s.[3]

Medical uses

The American Association of Clinical Endocrinologists[8] and the Royal College of Physicians[9] 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.[10]

About 65 mg of thyroid extract is equivalent to 100 ug of levothyroxine.[1]

Arguments against desiccated thyroid include:

  1. Desiccated thyroid preparations have a greater variability from batch to batch than synthetic ones.[10]
  2. Desiccated thyroid has roughly a 4:1 ratio of thyroxine (T4) to triiodothyronine (T3). In humans, the ratio is 11:1.[11]
  3. A combination of various ratios of T4 and T3 may not provide benefits over T4 alone. Some controlled trials have shown inconsistent benefits of various ratios of T4 and T3.[12][13]
  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.[14]
  5. The preference for "natural" treatment seems to stem from philosophical belief as opposed to science.[15]

Chemistry

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).[16] 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.[17]

History

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[18] 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 [19]

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.

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, 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. Dosage was regulated by improvement of symptoms.

Desiccated Thyroid became a commercial treatment option in 1934 with Westhroid,. 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.

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.[20]
  • 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%.[21][22][23][24] 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.[25]
  • 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.[26] 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,[27] but desiccated thyroid caused supraphysiologic levels of T3.[28] In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism.[29]
  • 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.[30]
  • 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.[29]

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. 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.

Names

This product is sometimes referred to as thyroid USP, thyroid BP. Brands differing only in binders and fillers.

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References
  1. "Thyroid Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 8 April 2019.
  2. "Thyroid desiccated Use During Pregnancy". Drugs.com. Retrieved 9 April 2019.
  3. Jameson, J. Larry; Groot, Leslie J. De (2010). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. p. 1608. ISBN 9781455711260.
  4. Thomas, John A.; Keenan, Edward J. (2012). Principles of Endocrine Pharmacology. Springer Science & Business Media. p. 78. ISBN 9781468450361.
  5. "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
  6. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  7. "Thyroid - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  8. Garber, JR; Cobin, RH; Gharib, H; Hennessey, JV; Klein, I; Mechanick, JI; Pessah-Pollack, R; Singer, PA; Woeber, KA for the American Association of Clinical Endocrinologists and the American Thyroid Association Taskforce on Hypothyroidism in Adults (December 2012). "Clinical Practice Guidelines for Hypothyroidism in Adults" (PDF). Thyroid. 22 (12): 1200–1235. doi:10.1089/thy.2012.0205. PMID 22954017. Archived from the original (PDF) on 2016-01-14. Retrieved 2014-11-08.
  9. "Thyroid disorders 'misdiagnosed'". BBC News. 2009-03-27. Retrieved 2009-03-30. 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.
  10. "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24.
  11. Repas, Thomas. Desiccated thyroid in the management of hypothyroidism: Part I.
  12. Baskin, HJ; Cobin, RH; Duick, DS; Gharib, H; Guttler, RB; Kaplan, MM; Segal, RL; American Association of Clinical, Endocrinologists (2002). "American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism" (PDF). Endocrine Practice. 8 (6): 457–69. doi:10.4158/1934-2403-8.6.457. PMID 15260011. Archived from the original (PDF) on 2015-12-08. Retrieved 2015-02-03.
  13. Clyde, PW; Harari, AE; Getka, EJ; Shakir, KM (10 December 2003). "Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial". JAMA. 290 (22): 2952–8. doi:10.1001/jama.290.22.2952. PMID 14665656.
  14. "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24.
  15. "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24.
  16. US Pharmacopeia Natural Formulary USP 37 N32 2014 Volume 3 May 1, 2014. The United States Pharmacopeial Convention. 2014. ISBN 9781936424221.
  17. Tory, David B. (2006). Remington The Science and Practice of Pharmacy, 21st edition. Philadelphia, PA: Lippincott Williams and Wilkins. pp. 1460, 1461. ISBN 0781763789.
  18. Murray GR. The life history of the first case of myxoedema treated by thyroid extract. Br Med J 1920;i:359-60.
  19. Burgess AM. Myxedema-- controlled by thyroid extract for fifty-two years: report of a case. Ann Internal Med 1946; 25:146.
  20. 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.
  21. Macgregor AG (February 1961). "Why does anybody use thyroid B.P.?". Lancet. 1 (7172): 329–32. doi:10.1016/s0140-6736(61)91498-2. PMID 13764789.
  22. Catz B, Ginsburg E, Salenger S (1962). "Clinically inactive thyroid U.S.P.: a preliminary report". N Engl J Med. 266: 136–137. doi:10.1056/nejm196201182660308.
  23. Pileggi VJ, Golub DJ, Lee ND (1965). "Determination of thyroxine and triiodothyronine in commercial preparations of desiccated thyroid and thyroid extract". J Clin Endocrinol Metab. 25: 949–56. doi:10.1210/jcem-25-7-949.
  24. Mangieri CN, Lund MH (January 1970). "Potency of United States Pharmacopeia desiccated thyroid tablets as determined by the antigoitrogenic assay in rats". J. Clin. Endocrinol. Metab. 30 (1): 102–4. doi:10.1210/jcem-30-1-102. PMID 5409525.
  25. Rees-Jones RW, Rolla AR, Larsen PR (February 1980). "Hormonal content of thyroid replacement preparations". JAMA. 243 (6): 549–50. doi:10.1001/jama.1980.03300320041023. PMID 7351788.
  26. Braverman LE, Ingbar SH, Sterling K (1970). "Conversion of thyroxine to triiodothyronine in athyreotic human subjects". J Clin Invest. 49: 855–64. doi:10.1172/jci106304.CS1 maint: multiple names: authors list (link)
  27. Saberi M, Utiger RD (1974). "Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy". J Clin Endocrinol Metab. 39: 923–7. doi:10.1210/jcem-39-5-923.
  28. Penny R, Frasier SD (January 1980). "Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid". American Journal of Diseases of Children. 134 (1): 16–8. doi:10.1001/archpedi.1980.02130130008003. PMID 7350782.
  29. Capiferri R, Evered D (March 1979). "Investigation and treatment of hypothyroidism". Clin Endocrinol Metab. 8 (1): 39–48. doi:10.1016/S0300-595X(79)80008-0. PMID 371874.
  30. Surks MI, Schadlow AR, Oppenheimer JH (1972). "A new radioimmunoassay for L-triiodothyronine: measurement in thyroid disease and in patients maintained on hormonal replacement". J Clin Invest. 51: 3104–13. doi:10.1172/jci107137.CS1 maint: multiple names: authors list (link)
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