A computational model of the human thyroid
Open accessAbstract
The thyroid, the largest gland in the endocrine system, secretes hormones that help promote bodily growth and development. This gland regulates hormonal secretion rate in spite of changes in dietary iodine which is a key ingredient in the hormone's biosynthesis. The thyroid relies on several feedback mechanisms for this regulation, and in this paper we use recent molecular-level and clinical observations to engineer a computational thyroid model. We use simulation and analysis to show that this models captures known aspects of thyroid physiology. We identify features in the model that are responsible for hormonal regulation, and use the model to identify and evaluate competing hypotheses associated with Wolff-Chaikoff escape.
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Degon et al. constructed a complex model describing intrafollicular iodine turnover in humans, including uptake, apical transport, organification, endocytosis, recycling, secretion of iodide, upregulation of TPO, TG, NIS and other proteins by TSH, feedback inhibition of H2O2 production and NIS by iodide, and of TG, NIS, and TPO by TG.
“Degon et al. constructed a complex model describing the intrafollicular iodine turnover in humans, including uptake, apical transport, organification, endocytosis, recycling, secretion of iodide, upregulation of TPO, TG, NIS and other proteins by TSH, feedback inhibition of H2O2 production and NIS by iodide, and of TG, NIS, and TPO by TG (276).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [276]
The Degon et al. model was used to understand and predict the condition of dietary iodine deficiency and Wolff-Chaikoff phenomena.
“The model was used to understand and predict the condition of dietary iodine deficiency and Wolff-Chaikoff phenomena.”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [276]
Cites
Pulsatile secretion of thyrotropin in man
GREENSPAN, S. L., KLIBANSK, A., SCHQENFELD, D., & RIDGWAY, E. C. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-3-661 · Cited by 140 · cited 1× · see citing works
“8 mU/dL mean, a circadian (modeled using a sinusoid), and 13 pulses a day [32] components.”
L-T <sub>4</sub> Bioequivalence and Hormone Replacement Studies via Feedback Control Simulations
Eisenberg, M., Samuels, M., & DiStefano, J. J. (2006) · Thyroid · doi:10.1089/thy.2006.16.1279 · Cited by 31 · see citing works
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TSH and thyrotropic agonists: key actors in thyroid homeostasis
Dietrich, J. W., Landgrafe, G., & Fotiadou, E. H. (2012) · Journal of Thyroid Research · doi:10.1155/2012/351864 · Cited by 146 · see citing works
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
Goede, S. L., Leow, M. K.-S., Smit, J. W. A., Klein, H. H., & Dietrich, J. W. (2014) · Bulletin of Mathematical Biology · doi:10.1007/s11538-014-9955-5 · Cited by 30 · see citing works
- Authors
- Degon, M., Chipkin, S. R., Hollot, C. V., Zoeller, R. T., & Chait, Y.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- University of Massachusetts Amherst (US)
- Corresponding author
- Chait, Yossi
- Venue
- Mathematical Biosciences
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 212
- Issue
- 1
- Pages
- 22-53
- ISSN
- 0025-5564 (ISSN-L)
- OpenAlex
- W2078119891
- Cited by
- 36
- References
- 2
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 7 · 2022: 2 · 2021: 3 · 2019: 5 · 2018: 3 · 2016: 3 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Mathematical Biosciences (publishedVersion)
- PubMed (publishedVersion)
- Scholarworks (University of Massachusetts Amherst) (submittedVersion, cc-by-nc-nd)
- ScholarWorks@UMassAmherst (University of Massachusetts Amherst) (submittedVersion, cc-by-nc-nd)
- ScholarWorks@UMassAmherst (University of Massachusetts Amherst) (submittedVersion)
- Scholarworks (University of Massachusetts Amherst) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES010026)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mathematical and Theoretical Epidemiology and Ecology Models
- Keywords
- thyroid gland, computational model, thyroid hormone regulation, iodine, thyroid-stimulating hormone, negative feedback, Wolff-Chaikoff effect, thyroid physiology, hormone biosynthesis, hormonal regulation
- MeSH terms
- Computer Simulation, Feedback, Humans, Models, Biological, Thyroid Gland, Thyroid Hormones
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