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Eur Thyroid J. 2016 Sep;5(3):171-179. Epub 2016 Aug 18.

Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease.

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Department of Nuclear Medicine, Klinikum Luedenscheid, Luedenscheid, Germany.
North Lakes Clinical, Ilkley, UK.
Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany; Ruhr Center for Rare Diseases (CeSER), Ruhr University of Bochum and Witten/Herdecke University, Bochum, Germany.



Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range.


We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease.


In the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = -0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample.


The euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification.


Thyroid homeostasis; Thyroid hormones; Thyrotropin; Thyrotropin feedback control

[Available on 2017-03-01]

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