Type 1 iodothyronine deiodinase in human physiology and disease

Maia, Ana Luiza; Goemann, Iuri Martin; Meyer, Erika L. Souza; Wajner, Simone Magagnin

doi:10.1530/joe-10-0481

Cited by 193 publications

(136 citation statements)

References 175 publications

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“…This could possibly stem from the stimulation by TSH of both type 1 (D 1 ) and type 2 (D 2 ) deiodinases mediated by a signalling process using cAMP (35,36,37,38,39). Interestingly, the correlation was strongest in untreated subjects and impaired in T 4 -treated patients, suggesting a role of TSH-modulated deiodination within the thyroid gland itself.…”

Section: Discussionmentioning

confidence: 99%

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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Objective: In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T 4 ) therapy. Design and methods: We have examined the interrelationships between free triiodothyronine (FT 3 ), free T 4 (FT 4 ) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T 4 and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis. Results: Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT 3 and FT 4 between untreated patients and L-T 4 groups. Total deiodinase activity (G D ) was positively correlated with TSH in untreated subjects. However, G D was significantly altered and the correlation was lost under increasing L-T 4 doses. Ninety-five per cent confidence intervals for FT 3 and FT 4 , when assessed in defined TSH concentration bands, differed significantly for L-T 4 -treated compared with untreated patients. Higher doses were often needed to restore FT 3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2. Conclusion: The data reveal disjoints between FT 4 -TSH feedback and T 3 production that persist even when sufficient T 4 apparently restores euthyroidism. T 4 treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

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Section: Discussionmentioning

confidence: 99%

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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“…This active T3 binds to THR (thyroid hormone receptor) in nucleus of cell where it activates gene leading to production of specific protein. 3 T3 also bind on cell membrane to integrin avβ3, stimulate sodium hydrogen antiportar, cell growth and angiogenesis. common cause.…”

Section: Introductionmentioning

confidence: 99%

Serum BUN and creatinine estimation in patients of overt hypothyroidism: a case control study

Kumari

Kumar²,

Keshari

et al. 2017

Int J Res Med Sci

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Background: Hypothyroidism or underactive thyroid or low thyroid is a common endocrine disorder characterized by low serum T3 (triiodothyronine), T4 (thyroxine) and raised TSH (thyroid stimulating hormone). Thyroid hormones are involved in renal development and hemodynamic, kidney structure and GFR (glomerular filtration rate). Aim of this study was to see the alteration of basic renal markers in patients of hypothyroidism.Methods: A total of seventy subjects were included in the study. Thirty-five were patients of hypothyroidism and thirty-five were age and sex matched normal controls. Serum T3, T4, TSH, creatinine and BUN (blood urea nitrogen) were estimated in both groups.Results: Serum T3, T4 were significantly decreased and TSH was significantly raised among cases as compared to controls. Mean value of serum creatinine and BUN were within normal range in both the groups but these values were significantly raised among cases as compared to controls with p value 0.02 and 0.003 respectively. Also, there was positive correlation of TSH with BUN and creatinine among cases.

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“…These Thematic reviews on deiodinases contain an overview of recent data about the intricate regulation of deiodinase activity in the control of plasma and intracellular TH action, including what happens when the actions of deiodinases are altered and how this occurs in different clinical settings (Dentice & Salvatore 2011, Maia 2011, Williams & Bassett 2011. Despite progress in our improved understanding of the structure and function of the deiodinases, much more remains to be discovered.…”

mentioning

confidence: 99%

Deiodinases: keeping the thyroid hormone supply in balance

Salvatore¹

2011

Journal of Endocrinology

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Thyroid hormones (TH) are iodinated compounds that are required for the normal growth, development and function of nearly all vertebrate tissues. They do this by modulating the expression of many genes that are tightly regulated in a specific tissue-and time-dependent fashion. The primary mechanism of TH action involves the binding of 3,5,3 0 -triiodothyronine (T 3 ) to its nuclear receptors in the context of regulatory TH response elements in target genes.In humans, the thyroid produces the pro-hormone thyroxine (T 4 ), and only about 20% of the active hormone, T 3 . T 4 is largely inactive until it is deiodinated to T 3 by the type 1 (D1) or 2 (D2) deiodinase. This reaction produces about 80% of the T 3 present in the circulation in healthy subjects. A third deiodinase, D3, exerts an opposing function, i.e. it catalyzes inner ring deiodination, thereby inactivating T 4 and T 3 . Given these functions, D3 is considered the major physiological inactivator and terminator of TH action at peripheral level.Why should we care about deiodinases and why they are so important? The role of deiodinases in TH homeostasis has become increasingly evident in the last 20 years, consequent to the cloning of the three members of the deiodinase family and generation of specific knock-out animals (Gereben et al. 2008, St Germain et al. 2009). Here, I present my perspective on the most important insights in this rapidly moving field.First, deiodinases are critical regulators of plasma T 3 concentrations. This is observed daily in thyroidectomized patients in whom L-T 4 therapy suffices to guarantee normal plasma T 3 levels. At a plasma level, deiodinases provide an important homeostatic mechanism, acting as the first line of defense when thyroid function is deranged or the supply of iodine is inadequate in order to maintain plasma T 4 or, at a minimum, plasma T 3 constant. It is not by chance that during hypothyroidism or iodine deficiency, the T 3 -producing enzyme D2 is upregulated, while levels of the inactivating enzyme D3 is decreased. An opposite regulation occurs during hyperthyroidism, due to the remarkable feature that T 4 itself is the most potent post-transcriptional inactivator of D2, while T 3 rapidly induces the D3 enzyme at transcriptional level. Thus, the actions of deiodinases are integrated in a homeostatic mechanism designed to maintain tissue T 3 content as normal as possible even in the face of altered serum hormone supplies.Second, deiodinases control TH action in a precise spatiotemporal fashion, according to the needs of selected tissues and cells. The T 4 concentration is generally quite stable in human plasma; even more stable is the T 3 concentration. During fetal development, when low plasma T 3 is necessary for the proper development and growth of fetal tissues, D3 is highly expressed in the placenta, the endometrium and in many embryonic tissues, with the consequence that free T 3 is almost ten-fold lower in fetal versus maternal plasma, while reverse T 3 is markedly increased.Deiodinases are also tigh...

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Type 1 iodothyronine deiodinase in human physiology and disease

Cited by 193 publications

References 175 publications

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Serum BUN and creatinine estimation in patients of overt hypothyroidism: a case control study

Deiodinases: keeping the thyroid hormone supply in balance

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