The homeostatic set point of the hypothalamus-pituitary-thyroid axis--maximum curvature theory for personalized euthyroid targets

The homeostatic set point of the hypothalamus-pituitary-thyroid axis--maximum curvature theory for personalized euthyroid targets
Title:
The homeostatic set point of the hypothalamus-pituitary-thyroid axis--maximum curvature theory for personalized euthyroid targets
Other Titles:
Theoretical Biology and Medical Modelling
Publication Date:
08 August 2014
Citation:
Leow MK, Goede SL. The homeostatic set point of the hypothalamus-pituitary-thyroid axis--maximum curvature theory for personalized euthyroid targets. Theor Biol Med Model. 2014;11:35. Published 2014 Aug 8. doi:10.1186/1742-4682-11-35
Abstract:
Background: Despite rendering serum free thyroxine (FT4) and thyrotropin (TSH) within the normal population ranges broadly defined as euthyroidism, many patients being treated for hyperthyroidism and hypothyroidism persistently experience subnormal well-being discordant from their pre-disease healthy euthyroid state. This suggests that intra-individual physiological optimal ranges are narrower than laboratory-quoted normal ranges and implies the existence of a homeostatic set point encoded in the hypothalamic-pituitary-thyroid (HPT) axis that is unique to every individual. Methods: We have previously shown that the dose-response characteristic of the hypothalamic-pituitary (HP) unit to circulating thyroid hormone levels follows a negative exponential curve. This led to the discovery that the normal reference intervals of TSH and FT4 fall within the 'knee' region of this curve where the maximum curvature of the exponential HP characteristic occurs. Based on this observation, we develop the theoretical framework localizing the position of euthyroid homeostasis over the point of maximum curvature of the HP characteristic. Results: The euthyroid set points of patients with primary hypothyroidism and hyperthyroidism can be readily derived from their calculated HP curve parameters using the parsimonious mathematical model above. It can be shown that every individual has a euthyroid set point that is unique and often different from other individuals. Conclusions: In this treatise, we provide evidence supporting a set point-based approach in tailoring euthyroid targets. Rendering FT4 and TSH within the laboratory normal ranges can be clinically suboptimal if these hormone levels are distant from the individualized euthyroid homeostatic set point. This mathematical technique permits the euthyroid set point to be realistically computed using an algorithm readily implementable for computer-aided calculations to facilitate precise targeted dosing of patients in this modern era of personalized medicine.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
The mice study was funded by a research grant administered by the Endocrine and Metabolic Society of Singapore (EMSS) which was awarded to A/Prof. Melvin Khee-Shing Leow. Financial support to cover the fee for Open Access publication came from core research funds of the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR).
Description:
ISSN:
1742-4682
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