Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings

Zoeller, R. T.; Rovet, J.

doi:10.1111/j.1365-2826.2004.01243.x

Cited by 606Thyroid Disorders and TreatmentsBirth, Development, and HealthDown syndrome and intellectual disability research

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings

Zoeller, R. T., Rovet, J.·2004·Journal of Neuroendocrinology

DOI 10.1111/j.1365-2826.2004.01243.x

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Abstract

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

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Early postnatal hypothyroidism affects cerebellar development, and this mechanism is thought to be the origin of motor deficits in primary congenital hypothyroidism.
“Early postnatal hypothyroidism affects cerebellar development, and this mechanism is thought to be the origin of motor deficits in primary CH (32).”
From Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings (2021) · cites this paper as [32]

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Authors: Zoeller, R. T., & Rovet, J.
Affiliations: University of Massachusetts Amherst (US)
University of Toronto (CA)
Corresponding author: Zoeller, R. T.
Rovet, J.
ORCID: Zoeller, R. T.
Rovet, J.
Venue: Journal of Neuroendocrinology
Publisher: Wiley
Published: 2004-10
Volume: 16
Issue: 10
Pages: 809-818
ISSN: 0953-8194 (ISSN-L)
1365-2826
DOI: 10.1111/j.1365-2826.2004.01243.x
OpenAlex: W2052693888
Cited by: 605
References: 167
Citations by year: 2026: 19 · 2025: 17 · 2024: 22 · 2023: 16 · 2022: 23 · 2021: 31 · 2020: 24 · 2019: 33 · 2018: 33 · 2017: 35 · 2016: 39 · 2015: 32 · 2014: 33 · 2013: 33 · 2012: 44
FWCI: 2.48
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 19 d)
Locations: Journal of Neuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: March of Dimes Foundation
National Institutes of Health
Canadian Institutes of Health Research
National Institute of Environmental Health Sciences (ES10026)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords: thyroid hormones, brain development, critical period, congenital hypothyroidism, maternal hypothyroidism, congenital hyperthyroidism, neuropsychological deficits, visual processing, strabismus, visuospatial ability, language and memory, developmental timing
MeSH terms: Animals, Brain, Female, Frontal Lobe, Humans, Pregnancy, Receptors, Thyroid Hormone, Thyroid Hormones

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Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings

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