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Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

ABSTRACT: INTRODUCTION:The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling. METHODS:We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control. These were compared with observed data points derived from clinical trials. RESULTS:A random mix of individual set points was reconstructed by simulative modelling with defined structural parameters. The pattern displayed by the cluster of hypothetical points resembled that observed in a natural control group. Moderate variation of the TSH-FT4 gradient over the functional range introduced further flexibility, implementing a scenario of adaptive set points. Such a scenario may be a realistic possibility for instance in treatment where relationships and equilibria between thyroid parameters are altered by various influences such as LT4 dose and conversion efficiency. CONCLUSIONS:We validated a physiologically based homeostatic model that permits simulative reconstruction of individual set points. This produced a pattern resembling the observed data under various conditions. Applied modelling, although still experimental at this stage, shows a potential to aid our physiological understanding of the interplay between TSH and thyroid hormones. It should eventually benefit personalised clinical decision making.

SUBMITTER: Hoermann R

PROVIDER: S-EPMC5695809 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

Hoermann Rudolf R Midgley John Edward Maurice JEM Larisch Rolf R Dietrich Johannes Wolfgang Christian JWC

PloS one 20171120 11

<h4>Introduction</h4>The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling.<h4>Methods</h4>We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control. These were compared with observed data points derived from clinical trials.<h4>Results</h4>A random m ...[more]

PMID: 29155897

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Project description:ObjectiveEvidence indicates that L-T4 in liquid and softgel capsule are absorbed better than tablets in hypothyroid patients, even when patients are under medications that impair the intestinal absorption of L-T4. However, no study has evaluated all three L-T4 formulations in the same hypothyroid patients. This study aims to fill this gap. The outcome was the degree of TSH change in the liquid and softgel formulations, using tablet L-T4 as the reference, regardless of sequence of formulation and regardless of whether patients were co-ingesting with interfering medications.MethodsWe recorded serum TSH levels in two groups of L-T4 replaced patients with primary hypothyroidism (23 subjects who did not co-ingest interfering medications, and 20 subjects who did). Either group of patients took one formulation of L-T4 at a time with variable sequences. In the first group, the median durations of exposure to tablet, liquid or softgel L-T4 were 14, 9 and 10?months, respectively. In the second group the corresponding durations were 13, 11 and 10?months, during which patients co-ingested interfering medications.ResultsIn the 23 patients, there were 78, 74 or 101 TSH determinations during liquid, softgel capsule or tablet L-T4 regimens. Serum TSH levels associated with liquid, capsule or tablet L-T4 were 1.62?±?0.51, 1.77?±?0.44?mU/L (P?=?0.049 vs liquid) or 2.38?±?0.69?mU/L (P?<?0.0001 vs liquid or capsule). Rates of TSH???2.50?mU/L were 97.4% (liquid), 95.9% (softgel) or 64.4% (tablet, P?<?0.0001 vs liquid or capsule). Rates of TSH???4.12?mU/L were 100%, 100% or 98.0%.In the 20 patients, the corresponding TSH determinations were 56, 57 and 41, and corresponding TSH levels were 2.74?±?0.98, 2.70?±?0.79 or 7.53?±?2.82?mU/L. Rates of TSH???2.50?mU/L were 51.8% (liquid), 47.4% (capsule, P?=?0.64) or 2.4% (tablet, P?<?0.0001 vs liquid or capsule). Rates of TSH???4.12?mU/L were 92.8% (liquid), 94.7% (capsule, P?=?0.68) or 12.2% (tablet, P?<?0.0001 vs liquid or capsule).ConclusionsL-T4 ingested as liquid solution or softgel capsule is more bioavailable compared to L-T4 ingested as tablet, and it is slightly superior to capsule L-T4 only in the absence of co-ingestion of interfering medications.

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Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

Publications

Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

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