In deze verhandeling laten de auteurs voor het eerst zien hoe met de TSH en de FT4 het persoonlijke setpoint berekend wordt. Dit setpoint is voor iedereen anders, ondanks dat de TSH en FT4 binnen de referentiewaarden vallen. Nu ligt eindelijk een snellere instelling op levothyroxine binnen handbereik.
The homeostatic set point of the hypothalamus-pituitary-thyroid axis - maximum curvature theory for personalized euthyroid targets
MK Leow, SL Goede
Theoretical Biology and Medical Modelling 2014, doi:10.1186/1742-4682-11-35
Published: 8 August 2014; Free access
A novel minimal mathematical model of the hypothalamus-pituitary-thyroid axis validated for individualized clinical applications
SL Goede, MK Leow, JW Smit, JW Dietrich
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.
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