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Cited by 48Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentClinical Laboratory Practices and Quality Control

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

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Hoermann, Rudolf, Midgley, John E. M., Larisch, Rolf, Dietrich, Johannes W.·2016·Frontiers in Endocrinology
DOI 10.3389/fendo.2016.00142PMC PMC5098235
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Abstract

Thyroid hormone concentrations only become sufficient to maintain a euthyroid state through appropriate stimulation by pituitary thyroid-stimulating hormone (TSH). In such a dynamic system under constant high pressure, guarding against overstimulation becomes vital. Therefore, several defensive mechanisms protect against accidental overstimulation, such as plasma protein binding, conversion of T4 into the more active T3, active transmembrane transport, counter-regulatory activities of reverse T3 and thyronamines, and negative hypothalamic-pituitary-thyroid feedback control of TSH. TSH has gained a dominant but misguided role in interpreting thyroid function testing in assuming that its exceptional sensitivity thereby translates into superior diagnostic performance. However, TSH-dependent thyroid disease classification is heavily influenced by statistical analytic techniques such as uni- or multivariate-defined normality. This demands a separation of its conjoint roles as a sensitive screening test and accurate diagnostic tool. Homeostatic equilibria (set points) in healthy subjects are less variable and do not follow a pattern of random variation, rather indicating signs of early and progressive homeostatic control across the euthyroid range. In the event of imminent thyroid failure with a reduced FT4 output per unit TSH, conversion efficiency increases in order to maintain FT3 stability. In such situations, T3 stability takes priority over set point maintenance. This suggests a concept of relational stability. These findings have important implications for both TSH reference limits and treatment targets for patients on levothyroxine. The use of archival markers is proposed to facilitate the homeostatic interpretation of all parameters.

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  1. [3]CLSI. Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline – Third Edition. CLSI Document C28-A3. Wayne, PA: Clinical and Laboratory Standards Institute (2010).

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Authors
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W.
Affiliations
  • Klinikum Lüdenscheid (DE)
  • Witten/Herdecke University (DE)
Corresponding author
Hoermann, Rudolf
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2016-11-07
Volume
7
Pages
142-142
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2016.00142
PMC
PMC5098235
OpenAlex
W2554592783
Cited by
48
References
110
Citations by year
2026: 1 · 2025: 13 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 6 · 2017: 4
FWCI
0.78
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
thyroid function, thyroid-stimulating hormone, homeostatic set point, thyroid hormone homeostasis, T4 to T3 conversion, reverse T3, thyronamines, thyroid function tests, thyroid disease classification

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