Abstract

The pituitary hormone, thyrotropin (TSH), is regarded as the primary biomarker for evaluating thyroid function and is useful in guiding treatment with levothyroxine for patients with hypothyroidism. The amplified response of TSH to slight changes in thyroid hormone levels provides a large and easily measured signal in the routine care setting. Laboratories provide reference ranges with upper and lower cutoffs for TSH to define normal thyroid function. The upper limit of the range, used to diagnose subclinical (mild) hypothyroidism, is itself a matter for debate, with authoritative guidelines recommending treatment to within the lower half of the range. Concomitant diseases, medications, supplements, age, gender, ethnicity, iodine status, time of day, time of year, autoantibodies, heterophilic antibodies, smoking, and other factors influence the level of TSH, or the performance of current TSH assays. The long-term prognostic implications of small deviations of TSH from the reference range are unclear. Correction of TSH to within the reference range does not always bring thyroid and other biomarkers into range and will not always resolve the patient's symptoms. Overt hypothyroidism requires intervention with levothyroxine. It remains important that physicians managing a patient with symptoms suggestive of thyroid disease consider all of the patient's relevant disease, lifestyle, and other factors before intervening on the basis of a marginally raised TSH level alone. Finally, these limitations of TSH testing mitigate against screening the population for the undoubtedly substantial prevalence of undiagnosed thyroid disease, until appropriately designed randomised trials have quantified the benefits and harms from this approach.

Highlights

  • Academic Editor: Noriyuki Koibuchi e pituitary hormone, thyrotropin (TSH), is regarded as the primary biomarker for evaluating thyroid function and is useful in guiding treatment with levothyroxine for patients with hypothyroidism. e amplified response of TSH to slight changes in thyroid hormone levels provides a large and measured signal in the routine care setting

  • Feedback circuits result in an inverse relationship between serum levels of thyroid hormones and TSH, i.e., low T4 and high T4 levels are associated with elevated and low TSH, respectively. e relationship between the magnitude of changes in serum TSH and the resulting magnitude of changes in circulating thyroid hormones is the key aspect of the regulation of thyroid function with regard to diagnosis of thyroid disorders. e precise nature of the relationship remains under debate, but the relationship between TSH and T4 approximates to an inverse log-linear relationship for most individuals, and this relationship becomes clearer for a given individual when more data points are available to define it [12,13,14]

  • Neonatal screening for congenital hypothyroidism is practised in many countries and is supported by guidelines [65]. ere is less of a consensus regarding screening of the population for undiagnosed thyroid disease, which may be common among the general population

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Summary

Serum TSH as the Principal Diagnostic Marker of Systemic Thyroid Status

Ethnicity influences thyroid hormone levels, which could produce an aberrant test where the local population that supplied subjects for determining the reference range is mainly of a different ethnicity to the patient [26]. Another study concluded that metformin treatment reduces serum TSH levels that are towards the upper limit of the reference range independent of anti-thyroid antibody status [32]. Current guidelines for the management of thyroid disease accept the need for a lower upper limit of the reference range during different stages of pregnancy, but differences between populations in the magnitude of the effect of pregnancy on thyroid hormone levels have been observed [8, 48]. A recent commentary concluded that we are not ready to develop guidelines in this area, due to a lack of consistently designed studies, interregional and intersubject variability in the effects observed, and difficulty in estimating exposure [62]. e ubiquity of potential endocrine disruptors in the environment, and growing evidence of harm associated with them, identifies this area as important for the future in multiple fields of medicine

Population Screening for Thyroid Dysfunction
Conclusions
Findings
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