Thyroidal and peripheral production of 3,5,3'-triiodothyronine in humans by multicompartmental analysis
Abstract
Multicompartmental analysis of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) kinetics based on the plasma disappearance curves of the two tracer hormones (J. J. DiStefano III, M. Jang, T. K. Malone, and M. Broutman. Endocrinology 110: 198-213, 1982 and J. J. DiStefano III, T. K. Malone, and M. Jang. Endocrinology 111: 108-117, 1982) was extended to include additional experimental data, namely, the appearance curve in plasma of labeled T3 generated in vivo from precursor T4. Kinetic analysis of data obtained in 14 studies carried out in normal subjects by using a composite six-pool model made it possible to quantify the contributions of the thyroid (3.3 micrograms.day-1.m-2) and the periphery (12.7 micrograms.day-1.m-2) to T3 production. T4 monodeiodination occurred mainly in peripheral tissues rapidly exchanging with plasma (10.7 micrograms T3.day-1.m-2), whereas only 2.0 micrograms T3.day-1.m-2 arose in slowly exchanging tissues. In contrast, if plasma disappearance curves only were analyzed, a value of 10.9 micrograms T3.day-1.m-2 was calculated for peripheral conversion in slowly exchanging tissues; this underscores the need for additional data, such as the [125I]T3 plasma appearance curve for the partition of central and peripheral production of T3.
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The physiological T4 to T3 secretion ratio by the thyroid gland itself is 16:1.
“I prefer this dose ratio, which is closest to the physiological T4 to T3 secretion ratio of 16:1 by the thyroid gland itself [81].”
From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [81]
Of total daily T3 production of about 33 μg in normal man, approximately 80% (about 26 μg) arises from peripheral conversion from T4 and only about 20% (approximately 6.5 μg) derives from direct thyroidal secretion.
“Of the total daily T3 production of about 33 l g in normal man, approximately 80% (about 26 l g) arises from peripheral conversion from T4, and only about 20% (approximately 6.5 l g) derives from direct thyroidal secretion (34).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [34]
SPINA-GD correlates with the conversion rate of slow tissue pools, as determined by isotope-based measurements in healthy volunteers.
“Physiologically, SPINA-GD correlates with the conversion rate of slow tissue pools (Figure 1D), as determined by isotope-based measurements in healthy volunteers (63).”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [63]
In humans, thyroxine (T4) is produced exclusively by the thyroid gland, with a daily production rate of about 100 μg at an average body surface area of 1.79 m2.
“Thyroxine (T4) is produced exclusively by the thyroid gland; its daily production rate is about 100 g at an average body surface area of 1.79 m 2 (56.2 g/day/m 2 ).”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [1]
In humans, daily triiodothyronine (T3) production is about 29 μg at a body surface area of 1.79 m2; about 20% is secreted by the thyroid gland and about 80% is generated extrathyroidally by 5-deiodination of T4.
“Daily production rate of triiodothyronine (T3) for a body surface area of 1.79 m 2 is about 29 g (16 g/day/m 2 ): 20% ( ϳ 6 g, or 3.3 g/day/m 2 ) is secreted by the thyroid gland, and 80% ( ϳ 23 g, or 12.7 g/day/m 2 ) is generated in extrathyroidal tissues by 5 -deiodination of T4 [1] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [1]
The molar ratio of T4 to T3 in thyroidal secretion is about 5.7:1 in rats and about 14:1 in humans.
“The molar ratio of T4 to T3 in thyroidal secretion is ϳ 5.7: 1 in rats and ϳ 14: 1 in humans [1] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [1]
Most studies fail to mimic the ratio of T4 to T3 secretion by the human thyroid gland under physiological conditions, which is close to 13:1 by weight.
“The wide variation in T4 to T3 dose ratio within and between RCTs constitutes a potential bias because most studies fail to mimic the ratio of T4 to T3 secretion by the human thyroid gland under physiological conditions, which is close to 13: 1 by weight [1] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [1]
The wide variation in T4 to T3 dose ratio within and between RCTs constitutes a potential bias.
“The wide variation in T4 to T3 dose ratio within and between RCTs constitutes a potential bias because most studies fail to mimic the ratio of T4 to T3 secretion by the human thyroid gland under physiological conditions, which is close to 13: 1 by weight [1] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [1]
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“I prefer this dose ratio, which is closest to the physiological T4 to T3 secretion ratio of 16:1 by the thyroid gland itself [81].”
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- Authors
- Pilo, A., Iervasi, G., Vitek, F., Ferdeghini, M., Cazzuola, F., & Bianchi, R.
- Affiliations
- University of Pisa (IT)
- ORCID
- Iervasi, G.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 1990-04-01
- Volume
- 258
- Issue
- 4
- Pages
- E715-E726
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W1930142341
- Cited by
- 185
- References
- 26
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 8 · 2019: 13 · 2018: 8 · 2017: 6 · 2016: 11 · 2015: 8 · 2014: 13 · 2013: 4 · 2012: 9
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- triiodothyronine, thyroxine, T4 to T3 conversion, plasma disappearance curve, thyroid hormone kinetics
- MeSH terms
- Adult, Female, Humans, Kinetics, Male, Mathematics, Middle Aged, Models, Biological, Organ Specificity, Reference Values, Thyroid Function Tests, Thyroid Gland, Thyroxine, Triiodothyronine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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