Follow-up to: when supplementing T4 & T3 for hashimotos, is it a concern that tsh is very low?
Question explored with the scientific record
when the patient is unable to convert t4 to t3 efficiently?
The short version: the evidence retrieved does not answer your question about impaired T4-to-T3 conversion in Hashimoto’s. The gap itself is the finding.
The retrieved studies are mostly about iron deficiency in rats [3], hemodialysis patients [1], and chicken embryos [4]. None of them test Hashimoto’s patients with documented poor T4-to-T3 conversion. The iron-deficiency rat study [3] is the closest mechanistic signal: iron-deficient rats had lower T3 at 4°C, and T4 supplementation failed to prevent hypothermia while T3 supplementation succeeded. That tells you iron status matters for deiodinase activity, but it does not tell you whether a Hashimoto’s patient with normal iron stores and impaired conversion benefits from adding T3.
The human studies on deiodinase regulation [9, 14] show that adrenergic signaling and inflammation (LPS) can upregulate or downregulate the enzymes that convert T4 to T3. That is relevant background, but no study in this set measures conversion efficiency in Hashimoto’s patients or compares T4-only to T4+T3 outcomes in that subgroup.
| What was studied | Population | Does it answer the question? |
|---|---|---|
| Iron deficiency impairs T4→T3 conversion [3] | Rats | No – different physiology, different cause |
| Hemodialysis lowers T3 [1] | Dialysis patients | No – different mechanism |
| LPS induces hypothalamic D2 [14] | Rats | No – mechanism only, no clinical outcome |
| Adrenergic synergy on D2 [9] | Rat brown adipocytes | No – cell culture, not patients |
My call: the evidence does not support or refute the hypothesis that impaired T4-to-T3 conversion in Hashimoto’s justifies combination T4+T3 therapy. The question has not been studied in the right population. Confidence: low, because the gap is large and the mechanistic studies are in non-human systems with different disease contexts.
Sources examined 17
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Transvenous Embolization of the Internal Spermatic Veins for the Treatment of Varicocele Scroti
The study characterizes the effect of chronic hemodialysis on thyroid function by evaluating the pituitary-thyroid axis in 28 patients before and after dialysis, revealing decreased T4, T3, and free T4 with unclear clinical significance and possible mechanisms involving reduced …
DOI: 10.1016/s0022-5347(17)53379-0 -
Iron, Thermoregulation, and Metabolic Rate
This article reviews how iron deficiency and iron deficiency anemia affect thermoregulation and metabolic rate in humans and rats, detailing increased sympathetic activity and altered thyroid hormone metabolism under cold exposure, with mixed findings on resting metabolic rate a…
DOI: 10.1080/10408399908500491 -
Hypothermia in iron deficiency due to altered triiodothyronine metabolism
Iron deficiency impairs conversion of thyroxine to triiodothyronine, reducing oxygen consumption and causing hypothermia in cold-exposed rats.
DOI: 10.1152/ajpregu.1980.239.5.r377 -
Thyroid hormone response to thyrotrophin releasing hormone(TRH) in the sex-linked dwarf chicken.
This study investigates the effects of thyrotrophin releasing hormone (TRH) on plasma levels of thyroid hormones in sex-linked dwarf chickens compared to normal chickens, revealing significant differences in hormone responses.
DOI: 10.1507/endocrj1954.33.675 -
Treatment of hyperthyroidism with a combination of methimazole and cholestyramine.
A randomized clinical trial evaluating whether adding cholestyramine to standard methimazole and propranolol therapy accelerates and enhances normalization of thyroid hormone levels in newly diagnosed hyperthyroid Graves' disease, showing greater and faster reductions with the c…
DOI: 10.1210/jcem.81.9.8784067 -
Thyroid hormone deiodinases in purified primary glial cell cultures
This study investigates the presence and regulation of iodothyronine deiodinase activity in purified primary glial cell cultures, specifically astrocytes and oligodendrocytes, derived from neonatal rat cerebri.
DOI: 10.1016/0006-8993(86)90852-8 -
Changes in Liver Iodothyronine 5′-Deiodinase Activity During Pregnancy and Lactation in the Rat
This study investigates the changes in liver iodothyronine 5'-deiodinase activity and circulating thyroid hormone levels during pregnancy and lactation in rats, revealing distinct patterns of thyroid hormone metabolism in these physiological states.
DOI: 10.1055/s-2007-1011868 -
Microcystin-LR Alters the Gene Transcription and Activities of Iodothyronine Deiodinases in the Hepatic Cells of Grass Carp ( Ctenopharyngodon Idella )
This study investigates the effects of microcystin-LR on the gene transcription and activities of iodothyronine deiodinases in the hepatic cells of grass carp, revealing significant alterations in enzyme activities without affecting cell viability.
DOI: 10.1002/jbt.21699 -
α 1 - and β-Adrenergic Agents Cause Synergistic Stimulation of the Iodothyronine Deiodinase in Rat Brown Adipocytes*
The study shows that alpha- and beta-adrenergic signaling synergistically stimulates type II iodothyronine deiodinase activity in rat brown adipocytes, with thyroid status modulating the magnitude of this synergy and implicating calcium and cAMP signaling in a mechanism that may…
DOI: 10.1210/endo-125-5-2502 -
Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction
In spontaneously hypertensive rats with experimentally induced myocardial infarction, a 4-week moderate-intensity treadmill program partially reversed MI-induced cardiac dysfunction and oxidative stress, associated with increased thioredoxin reductase, decreased type 3 iodothyro…
DOI: 10.1371/journal.pone.0222334 -
Differential expression of iodothyronine deiodinases in chicken tissues during the last week of embryonic development
This study investigates the expression and activity of iodothyronine deiodinases (D1, D2, D3) in various chicken tissues during the last week of embryonic development and the first two days post-hatch, revealing that D3 is the most widely expressed deiodinase, crucial for regula…
DOI: 10.1016/s0016-6480(02)00065-5 -
Inhibition of iodothyronine deiodinase by phenolphthalein dyes
This study investigates the structure-activity relationship of phenolphthalein derivatives as inhibitors of iodothyronine 5'-deiodinase, revealing that bromophenol blue is a potent competitive inhibitor.
DOI: 10.1016/0014-5793(82)80310-4 -
Human Breast Cancer Tissue Expresses High Level of Type 1 5′-Deiodinase
This study demonstrates that human breast cancer tissue frequently expresses high levels of type 1 iodothyronine deiodinase (D1) activity and DIO1 mRNA compared with non-cancerous breast tissue, with activity correlating with mRNA and showing distribution across tumor grades and…
DOI: 10.1089/thy.2006.0012 -
Lipopolysaccharide Induces Type 2 Iodothyronine Deiodinase in the Mediobasal Hypothalamus: Implications for the Nonthyroidal Illness Syndrome
This study investigates the regulation of type 2 iodothyronine deiodinase (D2) in the mediobasal hypothalamus by immune activation through lipopolysaccharide (LPS) administration, revealing a peak in D2 activity at 12 hours post-treatment and its implications for the nonthyroida…
DOI: 10.1210/en.2003-1439 -
Dynamic Nongenomic Actions of Thyroid Hormone in the Developing Rat Brain
This study investigates the dynamic nongenomic actions of thyroid hormone on actin polymerization and type II iodothyronine 5'-deiodinase activity in the developing rat brain, revealing that both T4 and rT3 can rapidly influence these processes, which are crucial for neuronal mi…
DOI: 10.1210/en.2005-1272 -
Northern analysis of type II iodothyronine deiodinase mRNA in rat harderian gland
This study investigates the expression of type II iodothyronine deiodinase mRNA in the rat Harderian gland and its regulation by isoproterenol, revealing that hypothyroid conditions and adrenergic stimulation significantly increase both mRNA levels and enzyme activity.
DOI: 10.1016/s0024-3205(98)00471-8 -
Short communication: Quantitative comparison of iodothyronine deiodinase I and II mRNA expression in ovine tissues
A short communication that quantifies DIO1 and DIO2 mRNA transcription across nine ovine tissues using RT-qPCR to map tissue-specific thyroid hormone activation and its relation to selenium status.
DOI: 10.1016/j.rvsc.2013.07.010