Her er en artikkel som nevner historien of thyroxin og Thyroid: http://jama.ama-assn.org/cgi/content/full/290/22/3002 (man må registrere seg, da kommer man inn)
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Combined T4 and T3 Therapy—Back to the Drawing Board
David S. Cooper, MD


JAMA. 2003;290:3002-3004.

Hormone replacement therapy" was originally reported by Murray, who in 1891 described the successful treatment of myxedema with injections of sheep thyroid extract.1 By 1898, therapy for this chronic, severely debilitating condition was hailed as "unparalleled by anything in the whole range of curative measures" by Osler.2 Seven decades later, desiccated thyroid was characterized by the standard thyroid textbook of the day as ". . . as perfect a form of therapy as any known to medicine. . . ."3 With the subsequent identification of thyroxine (T4) and triiodothyronine (T3) as the 2 major thyroid hormones, it was assumed that replacement therapies containing both compounds were more physiological than treatment with either alone. Thus, despite the availability of synthetic T4 in the early 1960s, the prescription of desiccated animal thyroid or synthetic combinations of T4 and T3 continued well into the 1970s.

However, following the report in 1970 that T4 was deiodinated in peripheral tissues to form the more biologically active T3,4 it was realized that T4 monotherapy would yield normal circulating levels of both T4 and T3.5 This fact, coupled with concerns about iatrogenic hyperthyroidism from a surge in serum T3 levels following the ingestion of T3-containing preparations, as well as variability in the hormonal content of desiccated thyroid, led to a progressive decrease in their use throughout the 1970s and 1980s.6 Review articles and guidelines on thyroid hormone therapy written in the 1990s all recommend synthetic T4 alone as the treatment of choice for patients with hypothyroidism.7-10 This advice was supported by a small study showing that patients treated with synthetic T4 alone have a quality of life that is similar to that of individuals without a history of thyroid disease.11

Nevertheless, virtually all primary care physicians have in their practices hypothyroid patients with persistent symptoms, despite adequate doses of T4 that are "proven" to be sufficient by normal serum thyroid hormone and thyroid-stimulating hormone (TSH [thyrotropin]) concentrations. This all too frequent scenario was quantified in a recent study showing that hypothyroid patients treated with T4 alone do not score as well on validated scales of psychological well-being and have more hypothyroid symptoms compared with euthyroid controls, despite having normal thyroid function results.12 Whether this finding represents the inability of T4 monotherapy to reproduce the exact hormonal milieu of a euthyroid individual or whether it is the result of having been "labeled" as having an illness (ie, hypothyroidism) remains uncertain.13-14

The use of T4 monotherapy as the treatment of choice for hypothyroidism was challenged in 1999 by a study comparing T4 alone with a combination of T4 and T3.15 In a randomized, blinded crossover design, hypothyroid patients taking the combination of T4 and T3 for 5 weeks had improved cognitive performance, mood, and physical well-being compared with a similar period when they received T4 alone.

..........
Treatment of patients with thyroid failure who have persistent hypothyroid or depressive symptoms while taking an adequate dose of T4 (defined by serum TSH levels between 0.5 and 2.5 mIU/L27) remains a major challenge. However, combined T4 plus T3 is not the answer.

After more than a century of successful treatment of hypothyroidism, it is fascinating that such seemingly simple hormonal replacement therapy would be the subject of so much continuing controversy. Before another century elapses, let us hope that the optimum treatment for all hypothyroid patients will be revealed by additional well-designed clinical trials using novel thyroid hormone preparations that precisely mirror normal thyroid physiology. Then, and only then, will thyroid replacement be ". . . as perfect a form of therapy as any known to medicine."3

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