Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects
TLDR
The present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man and raise the question of the extent to which the metabolic effect of T 4 is mediated through the peripheral generation of T3.Abstract:
Studies of the possibility that thyroxine (T4) is converted to 35,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-L-thyroxineT3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml) These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum When oral medication was enriched with (125)I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA(4)) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography The same results were obtained with a specially purified lot of radioactive T4 containing less than 01% T3 as a contaminant The identities of the (125)I-labeled T3 and TA(4) were verified by two-dimensional chromatography as well as by specific patterns of binding in serum The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA): in contrast the labeled TA(4) was bound by albumin and TBPA, but not by TBG To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administration, the sera of two additional patients were obtained 48 hr after 7-day courses of daily intravenous injections of a mixture of stable and (125)I-labeled T4 Both stable and labeled T3 were likewise found in these sera In contrast to earlier experiments in humans in which (131)I-labeled T3 was not definitively demonstrated in serum after a single intravenous injection of (131)I-labeled T4, the present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man These results raise once again the question of the extent to which the metabolic effect of T4 is mediated through the peripheral generation of T3read more
Citations
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Physiological and molecular basis of thyroid hormone action.
TL;DR: This review presents the major advances in knowledge of the molecular mechanisms of TH action and their implications for TH action in specific tissues, resistance to thyroid hormone syndrome, and genetically engineered mouse models.
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Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.
TL;DR: The goal of this review is to place the exciting advances that have occurred in understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context.
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Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association
Jeffrey R. Garber,Jeffrey R. Garber,Rhoda H. Cobin,Hossein Gharib,James V. Hennessey,Irwin Klein,Jeffrey I. Mechanick,Rachel Pessah-Pollack,Peter Singer,Kenneth A. Woeber +9 more
TL;DR: Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hyp Timothyroidism.
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Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement
Jacqueline Jonklaas,Antonio C. Bianco,Andrew J. Bauer,Kenneth D. Burman,Anne R. Cappola,Francesco S. Celi,David S. Cooper,Brian W. Kim,Robin P. Peeters,M. Sara Rosenthal,Anna M. Sawka +10 more
TL;DR: It is concluded that levothyroxine should remain the standard of care for treating hypothyroidism and no consistently strong evidence for the superiority of alternative preparations is found.
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Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling
Balázs Gereben,Ann Marie Zavacki,Scott Ribich,Brian W. Kim,Stephen A. Huang,Warner S. Simonides,Anikó Zeöld,Antonio C. Bianco,Antonio C. Bianco +8 more
TL;DR: It seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.
References
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Journal ArticleDOI
Determination of thyroxine utilizing the property of protein-binding.
TL;DR: A good correlation was obtained with the clinical status of patients studied, and the mean value expressed as thyroxine iodine for euthyroid individuals was 6.6±1.2, corresponding to a mean thyroxin level of 10.1 μg/100 ml.
Journal ArticleDOI
The identification of 3:5:3'-l-triiodothyronine in human plasma
Jack Gross,Rosalind Pitt-Rivers +1 more
Journal ArticleDOI
Simultaneous estimation of rates of thyroxine degradation and thyroid hormone synthesis.
TL;DR: A method has been devised for simultaneous estimation of the rates of degradation of thyroxine within the body and the rate of iodination of organic moieties within the thyroid gland.
Journal ArticleDOI
Determination of triiodothyronine concentration in human serum
TL;DR: From data and kinetic studies indicating a rapid turnover it may be inferred that T3 rather than T4 may be the more important hormone in health and in disease.
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