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The Iodotyrosine Deiodinase Defect
Published in Geraldo Medeiros-Neto, John Bruton Stanbury, Inherited Disorders of the Thyroid System, 2019
Geraldo Medeiros-Neto, John Bruton Stanbury
Subjects in this class of thyroid disorder share a defect in their capacity to deiodinate MIT and DIT. The deiodinase has been identified and characterized in liver, kidney, and other organs, in addition to the thyroid. Patients who have the defect lack deiodinase activity not only in the thyroid, but elsewhere as well, as disclosed by the finding that they do not deiodinate substrate when it is given parenterally. They do not deiodinate when on full replacement medication with thyroxine, so that the defect is not attributable to lowered deiodinase activity attendant upon hypothyroidism.
Metabolic Therapies for Muscle Injury
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
Ana V. Cintrón, Kenneth Cintron
Thyroid hormone (TH) plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells [15]. Thyroid hormone signaling is required for skeletal muscle development, contractile function and muscle regeneration. Current studies suggest that the dynamic control of thyroid hormone activity through the regulation of deiodinase expression can be harnessed to optimize myogenesis in patients with muscle diseases or injury [16].
Physiology of the Thyroid and Parathyroid Glands
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
At the tissue level, the biological activity of thyroid hormone is regulated by deiodinases (DIO). DIO-1 and DIO-2 are responsible for the generation of T3 from T4, whereas DIO 3-is the major inactivating enzyme, leading to an increase of reverse T3 (rT3).25 The ratio between T3 and rT3 (T3/rT3-ratio) is a sensitive indicator of peripheral thyroid hormone metabolism. The ratio is positively influenced by DIO-1 and DIO-2 and negatively by DIO-3. The T3/rT3-ratio is relatively independent of both thyroidal T4 production and thyroid hormone-binding protein variation in serum.25
Effect of sodium selenite on synaptic plasticity and neurogenesis impaired by hypothyroidism
Published in International Journal of Neuroscience, 2022
Ercan Babur, Özlem Canöz, Burak Tan, Cem Süer, Nurcan Dursun
Ptu is a thiourea derivative drug used in the treatment of hyperthyroidism. Its effect is shown by inhibition of thyroid peroxidase and 5-deiodinase and DIT-MIT binding. In our study, when free T4 levels were compared between groups, a statistically significant decrease was observed in the Ptu group compared to the control group. Se treatment did not affect fT4 thyroid hormone levels although fT3 levels increased by %60 in the Se treated rats. Chaonoine, et al demonstrated after short term thyroidectomy, serum T4 concentrations fell in both the Se-supplemented and Se-deficient rats [29]. Also, altered Se intake had no effect on the fall of serum T3. Esposito and colleagues showed that Se treatment for Hashimoto patients increased fT3 levels while decreasing fT4 levels. This effect of Se supplementation seems to be due to the increase of DIO 1 enzyme activity catalyzing the conversion of T4, T3 rather than the effect of selenium on thyroid hormone synthesis. Type 2 deiodinase enzyme is an important factor in adapting to changes in thyroid hormone levels in the central nervous system. When the thyroid hormone level decreases, such as hypothyroidism, DIO2 enzyme activity increases and attempts to maintenance thyroid hormone levels in the brain cells.
Thyroid dysfunction and survival in cancer patients treated with immune checkpoint inhibitors: analyses from a large single tertiary cancer center database
Published in Acta Oncologica, 2021
Ruth Percik, Yair Liel, Damien Urban, Jair Bar, Eytan Ben-Ami, Muhammad Abu Tailakh
Despite rare reports on severe thyrotoxicosis and even ‘thyroid storm’ in CPIs-treated patients [32], the typical presentation of CPI-induced TD is exceptionally clinically indolent. The mild clinical presentation of the thyrotoxic phase can be explained by concurrent alterations in thyroid hormone metabolism and peripheral response to thyroid hormones during the CPI-induced intense immune reaction, characteristic of the ‘euthyroid-sick syndrome’, which often accompanies inflammatory and no-inflammatory conditions [33]. Alterations in thyroid hormones and activity due to ‘euthyroid-sick syndrome’ include decreased expression of the thyroid hormone cell transporters MCT8 and MCT10, responsible for T4 uptake by peripheral tissues. Alterations in deiodinase expression result in reduced production of T3, simultaneous increased production of the biologically inactive metabolite, reverse-T3, and possibly a decrease in thyroid hormone receptors expression and their nuclear binding to DNA resulting in ‘tissue hypothyroidism’ [33]. Due to its mild clinical presentation, unless there are clinical awareness and specific laboratory surveillance, the early phase of thyroiditis can be easily missed. Levothyroxine should be initiated for patients with hypothyroidism and immunotherapy should not be interrupted. Finally, whereas most other drug-induced thyroid abnormalities result in the recovery of normal thyroid function, with only 5–20% of cases resulting in permanent hypothyroidism [19], most patients with CPI-induced TD progress to overt hypothyroidism requiring permanent treatment with a full replacement dose of thyroxine [17].
Getting the levothyroxine (LT4) dose right for adults with hypothyroidism: opportunities and challenges in the use of modern LT4 preparations
Published in Current Medical Research and Opinion, 2022
Ulrike Gottwald-Hostalek, Salman Razvi
This review has focused mainly on how the potential impact of the changing pharmaceutical regulatory environment has influenced the precise application of optimized LT4-based therapy for hypothyroidism. A number of other barriers to achieving this goal exist that are encountered commonly in routine endocrinological practice, and are discussed here briefly. For example, a minority (10–15%) of patients continue to report symptoms suggestive of hypothyroidism, despite successful return of TSH to within its reference range after titrated LT4 therapy7,44,45. In most (but not all) cases, careful clinical evaluation reveals another explanation for these symptoms, without increasing the LT4 dose46. A number of drugs, food products, and endogenous substances are known to interfere with the TSH test and may lead to aberrant results. More speculatively, it has been proposed that each patient has their own “set point” for thyroid hormone homeostasis, implying that the ideal TSH level for that individual may lie outside the range of “normal” values determined in the reference population used to validate the TSH test47,48. Peripheral deiodinases activate and deactivate thyroid hormones, and possible roles for polymorphisms in these enzymes, or iatrogenic or age-related changes in their activity, in determining an individual’s thyroid hormone status is a current active area of research49. Identifying and correcting issues such as these, where present, will provide clarity in interpreting the results of TSH tests, and facilitate achievement of the individual patient’s optimum LT4 dosage.