Desiccated thyroid extract

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Desiccated thyroid extract
Combination of
Levothyroxine Thyroid hormone
Liothyronine Thyroid hormone
Clinical data
Pregnancy cat.
  • A
Legal status
Routes Oral
Identifiers
CAS number  YesY
ATC code H03AA05
 YesY (what is this?)  (verify)

Desiccated thyroid or thyroid extract, refers to porcine or bovine thyroid glands, dried and powdered for therapeutic use.[1] Animal extract thyroid preparations were developed in the late 19th century, and are still in use today for the treatment of hypothyroidism.[citation needed] This product is sometimes referred to as "natural thyroid", "natural thyroid hormones", "pork thyroid", thyroid USP, thyroid BP, or by the name of a commercial brand, such as "Armour Thyroid" or "Nature-Throid" & "Westhroid".[2]

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).[3] 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.[4]

Brands include Forest Lab's Armour, and Naturethroid & Westhroid by RLC Labs. Canada's desiccated thyroid is made by ERFA Canada 2012 [5] and is called Thyroid. Also available is NP thyroid by Acella Pharmaceuticals.

All brands consist of desiccated porcine thyroid powder, differing only in binders and fillers[citation needed]. They contain a mixture of thyroid hormones: T4 (thyroxine) & T3 (triiodothyronine), in the proportions usually present in pig thyroids (approximately 80% T4 and 20% T3).[6]

Medical uses[edit]

Most endocrinologists and professional associations (such as the Royal College of Physicians[7]) oppose the use of desiccated thyroid. They recommend synthetic levothyroxine as the preferred treatment. Some practitioners refuse to use desiccated thyroid and will try to steer their patients away from it.[8]

Arguments against desiccated thyroid include:

  1. Desiccated thyroid preparations have a greater variability from batch to batch than synthetic ones.[8] Proponents of natural thyroid argue that synthetic preparations also suffer from variability.[9]
  2. Desiccated thyroid has roughly a 4:1 ratio of thyroxine (T4) to triiodothyronine (T3). In humans, the ratio is 11:1.[10] However, after peripheral conversion of T4 to T3, the ratio is closer to 3:1.[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][14] However, a common variation in the DI02 gene may predict enhanced response to combined T4 & T3 therapy.[15] The merits of T4 & T3 versus T4 alone remain controversial among the endocrinology community.
  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.[16] However, there is no convincing evidence that suppression of TSH leads to an increased risk of osteoporosis or other illness.[17][18]
  5. The preference for "natural" treatment seems to stem from philosophical belief as opposed to science.[19]

History[edit]

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[20] 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 [21]

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]

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] 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] Dosage was regulated by improvement of symptoms.

Desiccated Thyroid became a commercial treatment option in 1934 with Westhroid,[citation needed]. In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by levothyroxine (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 levothyroxine or T4/T3 combinations than desiccated thyroid extract.[citation needed]

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.[22]
  • 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%.[23][24][25][26] It was hoped that better dosing precision with levothyroxine 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.[27]
  • 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.[28] 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,[29] but desiccated thyroid caused supraphysiologic levels of T3.[30] In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism.[31]
  • It was discovered that a healthy person varied the amount of T3 produced from T4 in response to changing needs and conditions[citation needed] and it seemed wiser not to bypass this control system by providing larger amounts of T3 than were naturally produced each day[improper synthesis?].
  • Furthermore, when T3 could be measured, it was discovered that thyroid extract and synthetic combinations of T4 and T3[contradiction] produced significantly greater fluctuations of T3 throughout the day than occurred in healthy people or hypothyroid people treated with thyroxine alone.[32]
  • 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.[31]

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] Blood levels of thyroid hormones and TSH were found to be the best predictors of objective benefits from thyroid replacement[improper synthesis?]: those with the most severe measurable deficiency enjoyed the most dramatic and sustained benefits.[citation needed] 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]

Society and culture[edit]

A number of claims by patients about thyroid extract:

  • Patients prefer thyroid extract as they experience a resolution of lingering hypothyroid symptoms, such as low grade chronic depression.
  • Thyroid extract is a superior treatment to levothyroxine as it contains T4, T3, diiodothyronine (T2), monoiodothyronine (T1), and calcitonin.[33] In comparison, synthetic treatments contain only T4 or, rarely, T4 and T3 combined.
  • The product is made from hormones as they occur in nature, as opposed to synthetic laboratory produced mimics of the original structure. The T4 and T3 extracted from the glands of animals are bound to the carrier protein TBG, which is the same form that more than 99% of these hormones are in when transported throughout the human body.[34] Synthetic versions are in the free, unbound form.
  • Doses should be increased until symptoms are relieved, even when this leads to a suppression of TSH.

References[edit]

  1. ^ Professional Guide to Drugs- A Reference for Doctors, Nurses, Dentists, Pharmacists- Anyone Who Prescribes, Administers, or Takes Medicines. Cal State Long Beach Library: Intermed Communications Books. 1982. p. 592. ISBN 0916730514. 
  2. ^ "Thyroid, Oral. Version 2012, Issue 1". RelayClinical Education. February 2012. 
  3. ^ US Pharmacopeia Natural Formulary USP 37 N32 2014 Volume 3 May 1, 2014. The United States Pharmacopeial Convention. 2014. ISBN 9781936424221. 
  4. ^ Tory, David B. (2006). Remington The Science and Practice of Pharmacy, 21st edition. Philadelphia, PA: Lippincott Williams and Wilkins. pp. 1460, 1461. ISBN 0781763789. 
  5. ^ http://www.eci2012.net/
  6. ^ 2008 AHFS Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists. 2008. pp. 3308, 3309. ISBN 978-1-58528206-7. 
  7. ^ "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." 
  8. ^ a b "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24. 
  9. ^ Lowe, JC. Stability, Effectiveness, and Safety of Desiccated Thyroid vs Levothyroxine: A Rebuttal to the British Thyroid Association. Thyroid Science 4(3): C1 -12, 2009 .
  10. ^ Repas, Thomas. Desiccated thyroid in the management of hypothyroidism: Part I.
  11. ^ PMID 16982586
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ Panicker, V; Saravanan, P; Vaidya, B; Evans, J; Hattersley, A. T.; Frayling, T. M.; Dayan, C. M. (2009). "Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients". The Journal of clinical endocrinology and metabolism 94 (5): 1623–9. doi:10.1210/jc.2008-1301. PMID 19190113.  edit
  16. ^ "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24. 
  17. ^ Bauer, D. C.; Nevitt, M. C.; Ettinger, B; Stone, K (1997). "Low thyrotropin levels are not associated with bone loss in older women: A prospective study". The Journal of clinical endocrinology and metabolism 82 (9): 2931–6. doi:10.1210/jcem.82.9.4229. PMID 9284722.  edit
  18. ^ Leese, G. P.; Jung, R. T.; Guthrie, C; Waugh, N; Browning, M. C. (1992). "Morbidity in patients on L-thyroxine: A comparison of those with a normal TSH to those with a suppressed TSH". Clinical endocrinology 37 (6): 500–3. PMID 1286519.  edit
  19. ^ "Endocrine Today Blog". Endocrinetoday.com. Retrieved 2014-07-24. 
  20. ^ Murray GR. The life history of the first case of myxoedema treated by thyroid extract. Br Med J 1920;i:359-60.
  21. ^ Burgess AM. Myxedema-- controlled by thyroid extract for fifty-two years: report of a case. Ann Internal Med 1946; 25:146.
  22. ^ 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.
  23. ^ Macgregor AG (February 1961). "Why does anybody use thyroid B.P.?". Lancet 1 (7172): 329–32. PMID 13764789. 
  24. ^ Catz B, Ginsburg E, Salenger S. Clinically inactive thyroid U.S.P.: a preliminary report. New Engl J Med 1962; 266:136.
  25. ^ 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.
  26. ^ 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. 
  27. ^ 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. 
  28. ^ Braverman LE, Ingbar SH, Sterling K. Conversion of thyroxine to triiodothyronine in athyreotic human subjects. J Clin Invest 1970; 49:855-64.
  29. ^ Saberi M, Utiger RD. Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy. J Clin Endocrinol Metab 1974; 39:923-7.
  30. ^ 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. 
  31. ^ a b 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. 
  32. ^ 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.
  33. ^ "T4-only meds like Synthroid do NOT work, exclaim many patients!". Stop The Thyroid Madness. 2014-06-17. Retrieved 2014-07-24. 
  34. ^ "notesonthyroidfunction". People.upei.ca. Retrieved 2014-07-24. 

External links[edit]