Recent discoveries have challenged the diagnostic dominance of thyroid-stimulating hormone (TSH), especially in treatment of hypothyroid patients with oral thyroid hormone. The prominent role of free thyroid hormone assay (FT4 and FT3) measurements as determinants of satisfactory treatment in themselves or through a ratio as an indicator of T4 conversion to T3 is now beginning to be recognised after a long period of relative neglect. The new findings inform the best way to regain health, when combined with the equally key role of patient presentation. In order to rehearse the developments that have led to this re-evaluation, this chapter is devoted to a narrative on the history of thyroid function diagnosis and the tests used to optimise medication for hypothyroidism. It is to be read in the light of arguments elsewhere in this book that re-examine the physiology of thyroid function and malfunction and its effect on the choice of diagnosis and treatment. I shall initially comment briefly on progress in these activities from the viewpoint of a physical chemist/biochemist and inventor of the labelled one-step analogue and labelled antibody-free thyroid hormone assays currently used routinely. Since 1985, the sensitive TSH assay has become a powerful (and sometimes claimed as only needed) determinant of hypothyroidism and satisfactory treatment. However, the hitherto dominant role of sensitive TSH assays in controlling therapy has become suspect. Accordingly, in therapy for hormone supplementation, it is becoming clear that the role of TSH has been overstated and the free thyroid hormone assays (FT4 and FT3) play far more important and decisive roles in the diagnostic process. Consequently, the consistency of their performance has become a key determinant of their diagnostic value. Regrettably, it appears that, while TSH assays have been better, though not completely, harmonised, FT4 and especially FT3 assays from different manufacturers still display considerable variability in performance. Almost all do not obey the fundamental requirements that demonstrate satisfactory performance. There is little doubt that, unlike the perceived need for accurate TSH testing, failure to similarly redesign FT4/FT3 test performance has led to a loss of impetus owing to the overwhelming dominance of TSH as a favoured diagnostic. Given the present situation, this highlights the shortcomings of regulators and manufacturers of such assays, which have permitted their inconsistent measurements. In addition, historical allegations of basic inadequacy of the underlying technique have arisen, consequently becoming unquestioned certainties embedded in the literature. These false criticisms have sharply illuminated the lack of physical chemistry understanding underlying these methods. The basic fallacies of these allegations are revealed here. In addition, the paucity of reported use of assays, which are soundly based, invites further comment on why they do not figure more frequently in the literature. The influence of integrated diagnostic platforms and the resulting restriction of an individual choice of tests are postulated as contributing factors. It would also seem that in addition financial considerations may dominate platform choice, together with the apparent indifference of users (other than complaint as to the quality of the products they engage with). Finally, I make suggestions as to how this presently unsatisfactory state of affairs could be improved.

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

The New Paradigm for Thyroid Function Diagnosis and Treatment: Conceptual and Technical Barriers to Consistent Outcomes

  • John E. Midgley,
  • Rudolf Hoermann,
  • Johannes W. Dietrich

摘要

Recent discoveries have challenged the diagnostic dominance of thyroid-stimulating hormone (TSH), especially in treatment of hypothyroid patients with oral thyroid hormone. The prominent role of free thyroid hormone assay (FT4 and FT3) measurements as determinants of satisfactory treatment in themselves or through a ratio as an indicator of T4 conversion to T3 is now beginning to be recognised after a long period of relative neglect. The new findings inform the best way to regain health, when combined with the equally key role of patient presentation. In order to rehearse the developments that have led to this re-evaluation, this chapter is devoted to a narrative on the history of thyroid function diagnosis and the tests used to optimise medication for hypothyroidism. It is to be read in the light of arguments elsewhere in this book that re-examine the physiology of thyroid function and malfunction and its effect on the choice of diagnosis and treatment. I shall initially comment briefly on progress in these activities from the viewpoint of a physical chemist/biochemist and inventor of the labelled one-step analogue and labelled antibody-free thyroid hormone assays currently used routinely. Since 1985, the sensitive TSH assay has become a powerful (and sometimes claimed as only needed) determinant of hypothyroidism and satisfactory treatment. However, the hitherto dominant role of sensitive TSH assays in controlling therapy has become suspect. Accordingly, in therapy for hormone supplementation, it is becoming clear that the role of TSH has been overstated and the free thyroid hormone assays (FT4 and FT3) play far more important and decisive roles in the diagnostic process. Consequently, the consistency of their performance has become a key determinant of their diagnostic value. Regrettably, it appears that, while TSH assays have been better, though not completely, harmonised, FT4 and especially FT3 assays from different manufacturers still display considerable variability in performance. Almost all do not obey the fundamental requirements that demonstrate satisfactory performance. There is little doubt that, unlike the perceived need for accurate TSH testing, failure to similarly redesign FT4/FT3 test performance has led to a loss of impetus owing to the overwhelming dominance of TSH as a favoured diagnostic. Given the present situation, this highlights the shortcomings of regulators and manufacturers of such assays, which have permitted their inconsistent measurements. In addition, historical allegations of basic inadequacy of the underlying technique have arisen, consequently becoming unquestioned certainties embedded in the literature. These false criticisms have sharply illuminated the lack of physical chemistry understanding underlying these methods. The basic fallacies of these allegations are revealed here. In addition, the paucity of reported use of assays, which are soundly based, invites further comment on why they do not figure more frequently in the literature. The influence of integrated diagnostic platforms and the resulting restriction of an individual choice of tests are postulated as contributing factors. It would also seem that in addition financial considerations may dominate platform choice, together with the apparent indifference of users (other than complaint as to the quality of the products they engage with). Finally, I make suggestions as to how this presently unsatisfactory state of affairs could be improved.