scholarly journals High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

2015 ◽  
Vol 4 (Suppl. 1) ◽  
pp. 87-91 ◽  
Author(s):  
Eva K. Wirth ◽  
Eddy Rijntjes ◽  
Franziska Meyer ◽  
Josef Köhrle ◽  
Ulrich Schweizer
Keyword(s):  
Thyroid Hormone ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Psychomotor Retardation ◽  
Monocarboxylate Transporter ◽  
Type I ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Mct8 Deficiency ◽  
Deficient Mice

Background: The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods: We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

scholarly journals Tissue Thyroid Hormone Levels in Critical Illness

2005 ◽  
Vol 90 (12) ◽  
pp. 6498-6507 ◽  
Author(s):  
Robin P. Peeters ◽  
Serge van der Geyten ◽  
Pieter J. Wouters ◽  
Veerle M. Darras ◽  
Hans van Toor ◽  
...  
Keyword(s):  
Critical Illness ◽  
Thyroid Hormone ◽  
Hormone Treatment ◽  
Monocarboxylate Transporter ◽  
Total Serum ◽  
Tissue Specific ◽  
Hormone Levels ◽  
Serum T3 ◽  
Serum Thyroid Hormone ◽  
Thyroid Hormone Levels

Context: Pronounced alterations in serum thyroid hormone levels occur during critical illness. T3 decreases and rT3 increases, the magnitudes of which are related to the severity of disease. It is unclear whether these changes are associated with decreased tissue T3 concentrations and, thus, reduced thyroid hormone bioactivity. Patients and Study Questions: We therefore investigated, in 79 patients who died after intensive care and who did or did not receive thyroid hormone treatment, whether total serum thyroid hormone levels correspond to tissue levels in liver and muscle. Furthermore, we investigated the relationship between tissue thyroid hormone levels, deiodinase activities, and monocarboxylate transporter 8 expression. Results: Tissue iodothyronine levels were positively correlated with serum levels, indicating that the decrease in serum T3 during illness is associated with decreased levels of tissue T3. Higher serum T3 levels in patients who received thyroid hormone treatment were accompanied by higher levels of liver and muscle T3, with evidence for tissue-specific regulation. Tissue rT3 and the T3/rT3 ratio were correlated with tissue deiodinase activities. Monocarboxylate transporter 8 expression was not related to the ratio of the serum over tissue concentration of the different iodothyronines. Conclusion: Our results suggest that, in addition to changes in the hypothalamus-pituitary-thyroid axis, tissue-specific mechanisms are involved in the reduced supply of bioactive thyroid hormone in critical illness.

scholarly journals Iodothyronine deiodinases and the control of plasma and tissue thyroid hormone levels in hyperthyroid tilapia (Oreochromis niloticus)

2005 ◽  
Vol 184 (3) ◽  
pp. 467-479 ◽  
Author(s):  
S Van der Geyten ◽  
N Byamungu ◽  
G E Reyns ◽  
E R Kühn ◽  
V M Darras
Keyword(s):  
Thyroid Hormone ◽  
Oreochromis Niloticus ◽  
Degradation Mechanism ◽  
Current Data ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Thyroid status is one of the most potent regulators of peripheral thyroid hormone metabolism in vertebrates. Despite this, the few papers that have been published concerning the role of thyroid hormones in the regulation of thyroid function in fish often offer conflicting data. We therefore set out to investigate the effects of tetraiodothyronine (thyroxine) (T4) or tri-iodothyronine (T3) supplementation (48 p.p.m.) via the food on plasma and tissue thyroid hormone levels as well as iodothyronine deiodinase (D) activities in the Nile tilapia (Oreochromis niloticus). T4 supplementation did not induce a hyperthyroid state and subsequently had no effects on the thyroid hormone parameters measured, with the liver as the sole notable exception. In T4-fed tilapias, the hepatic T4 levels increased substantially, and this was accompanied by an increase in in vitro type I deiodinase (D1) activity. Although the lack of effect of T4 supplementation could be partially explained by an inefficient uptake of T4 from the gut, our current data suggest that also the increased conversion of T4 into reverse (r)T3 by the D1 present in the liver plays an important role in this respect. In addition, T3 supplementation increased plasma T3 and decreased plasma T4 concentrations. T3 levels were also increased in the liver, brain, kidney, gill and white muscle, but without affecting local T4 concentrations. However, this increase in T3 availability remained without effect on D1 activity in liver and kidney. This observation, together with the 6-n-propylthiouracyl (PTU) insensitivity of the D1 enzyme in fish, sets the D1 in teleost fish clearly apart from its mammalian and avian counterparts. The changes in hepatic deiodinases confirm the role of the liver as an important T3-regulating tissue. However, the very short plasma half-life of exogenously administered T3 implies the existence of an efficient T3 clearing/degradation mechanism other than deiodination.

scholarly journals Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 802-809 ◽  
Author(s):  
Marija Trajkovic-Arsic ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
Edith C. H. Friesema ◽  
Bernhard Schlott ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Psychomotor Retardation ◽  
High Serum ◽  
Monocarboxylate Transporter ◽  
Iodothyronine Deiodinase ◽  
Serum T4 ◽  
Mct8 Deficiency ◽  
Low Serum

Patients carrying inactivating mutations in the gene encoding the thyroid hormone transporting monocarboxylate transporter (MCT)-8 suffer from a severe form of psychomotor retardation and exhibit abnormal serum thyroid hormone levels. The thyroidal phenotype characterized by high-serum T3 and low-serum T4 levels is also found in mice mutants deficient in MCT8 although the cause of these abnormalities is still unknown. Here we describe the consequences of MCT8 deficiency for renal thyroid hormone transport, metabolism, and function by studying MCT8 null mice and wild-type littermates. Whereas serum and urinary parameters do not indicate a strongly altered renal function, a pronounced induction of iodothyronine deiodinase type 1 expression together with increased renal T3 and T4 content point to a general hyperthyroid state of the kidneys in the absence of MCT8. Surprisingly, accumulation of peripherally injected T4 and T3 into the kidneys was found to be enhanced in the absence of MCT8, indicating that MCT8 deficiency either directly interferes with the renal efflux of thyroid hormones or activates indirectly other renal thyroid hormone transporters that preferentially mediate the renal uptake of thyroid hormones. Our findings indicate that the enhanced uptake and accumulation of T4 in the kidneys of MCT8 null mice together with the increased renal conversion of T4 into T3 by increased renal deiodinase type 1 activities contributes to the generation of the low-serum T4 and the increase in circulating T3 levels, a hallmark of MCT8 deficiency.

scholarly journals Low TSH levels are not associated with osteoporosis in childhood

2007 ◽  
Vol 157 (2) ◽  
pp. 221-223 ◽  
Author(s):  
Anastasios Papadimitriou ◽  
Dimitrios T Papadimitriou ◽  
Anna Papadopoulou ◽  
Polyxeni Nicolaidou ◽  
Andreas Fretzayas
Keyword(s):  
Thyroid Hormone ◽  
Calcium Phosphate ◽  
Bone Metabolism ◽  
Serum Calcium ◽  
Type I ◽  
Normal Range ◽  
Hormone Levels ◽  
Amino Terminal ◽  
Thyroid Hormone Levels ◽  
Tsh Levels

Introduction: A recent study on TSH receptor (TSHR) null mice suggested that skeletal loss occurring in hyperthyroidism is caused by the low TSH rather than high thyroid hormone levels. The aim of this study was to examine whether low TSH results in osteoporosis in the human. Subjects and methods: We determined bone mineral density (BMD) and markers of bone metabolism in two male siblings aged 9.8 and 6.8 years with isolated TSH deficiency, due to a mutation of the TSH β-subunit gene. BMD was measured in the lumbar spine (L1–L4) by dual-energy X-ray absorptiometry. Laboratory investigation included the determination of serum calcium, phosphate, 25-hydroxy-vitamin D, parathyroid hormone concentrations, and urine calcium (Ca)/creatinine (Cr) ratio. Osteoblast activity was measured by serum bone alkaline phosphatase and osteocalcin levels, and osteoclast activity by urine cross-linked amino-terminal, carboxy-terminal telopeptides of type I collagen and deoxypyridinoline concentrations. Results: BMD of both patients was within the normal range for age and sex; z-scores were −0.55 and −0.23 for patients 1 and 2 respectively. Serum calcium, phosphate, urine Ca/Cr ratio, and specific markers of bone metabolism were also within normal range. Conclusion: In childhood, chronic extremely low TSH levels, in the face of normal thyroid hormone levels, are not related to bone loss.

scholarly journals Oligodendroglial Lineage Cells in Thyroid Hormone-Deprived Conditions

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Min Joung Kim ◽  
Steven Petratos
Keyword(s):  
Thyroid Hormone ◽  
Psychomotor Retardation ◽  
Monocarboxylate Transporter ◽  
Therapeutic Effects ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Extracellular Transport ◽  
Synaptic Dynamics ◽  
Mct8 Deficiency

Oligodendrocytes are supporting glial cells that ensure the metabolism and homeostasis of neurons with specific synaptic axoglial interactions in the central nervous system. These require key myelinating glial trophic signals important for growth and metabolism. Thyroid hormone (TH) is one such trophic signal that regulates oligodendrocyte maturation, myelination, and oligodendroglial synaptic dynamics via either genomic or nongenomic pathways. The intracellular and extracellular transport of TH is facilitated by a specific transmembrane transporter known as the monocarboxylate transporter 8 (MCT8). Dysfunction of the MCT8 due to mutation, inhibition, or downregulation during brain development leads to inherited hypomyelination, which manifests as psychomotor retardation in the X-linked inherited Allan-Herndon-Dudley syndrome (AHDS). In particular, oligodendroglial-specific MCT8 deficiency may restrict the intracellular T3 availability, culminating in deficient metabolic communication between the oligodendrocytes and the neurons they ensheath, potentially promulgating neurodegenerative adult diseases such as multiple sclerosis (MS). Based on the therapeutic effects exhibited by TH in various preclinical studies, particularly related to its remyelinating potential, TH has now entered the initial stages of a clinical trial to test the therapeutic efficacy in relapsing-remitting MS patients (NCT02506751). However, TH analogs, such as DITPA or Triac, may well serve as future therapeutic options to rescue mature oligodendrocytes and/or promote oligodendrocyte precursor cell differentiation in an environment of MCT8 deficiency within the CNS. This review outlines the therapeutic strategies to overcome the differentiation blockade of oligodendrocyte precursors and maintain mature axoglial interactions in TH-deprived conditions.

scholarly journals Evaluation of Thyroid Hormones Levels in Libyan Patients with Chronic Renal Failure Before and AFTER Maintenance Hemodialysis

2021 ◽  
Vol 3 (2) ◽  
pp. 01-03
Author(s):  
Aisha Muhammed
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Thyroid Hormone ◽  
Serum Levels ◽  
Normal Range ◽  
Hormone Levels ◽  
Kidney Dialysis ◽  
Before And After ◽  
Thyroid Hormone Levels

Data from recent studies revealed that kidney diseases might affect the thyroid function in various ways. A variety of alterations in thyroid hormone levels and metabolism have also been reported in patients with chronic renal failure (CRF) in some studied population. In addition, it was reported that serum levels of both T3 and T4 might altered immediately after a hemodialysis (HD) treatment than before. Therefore, this study was aimed to investigate the level of triiodothyronine (T3) and thyroxine (T4) in CRF Libyan patients before and after HD. This study was carried out on 46 CRF patients (30 male and 16 female) with a mean age of 47.46 ±15.75 years. These patients were treated at the hemodialysis unit of Educational Central Zelitin Hospital, Zelitin, Libya. None of these patients apparently have any thyroid problems and no history of drug intake that may affect thyroid function. Blood samples were taken from each patient to measure serum levels of T3 and T4, before and after HD. In addition, the effect of several variables include age, gender, body mass index (BMI), presence of both hypertension and, diabetes mellitus and duration of kidney dialysis on serum levels of T3and T4 before and after HD were also studied. After HD, there was a statistically significant increase in the serum levels of T3, T4. The age, gender, BMI, duration of kidney dialysis and the presence of hypertension and diabetes mellitus did not have any significant effect on the serum level of T3 and T4 before and after HD. However, the serum levels of T3 and T4 were still in the normal range in these examined patients either before or after HD. From these findings, it can be concluded that these CRF patients may be in a euthyroid state, because the serum levels of T3 and T4 were in the normal range. In addition, HD was seem to improve the T3 and T4 thyroid hormone concentrations, suggesting that HD might activate the secretion of thyroid glandand catabolism. The other variables did not play any role in thyroid hormone levels in these patients either before or after HD. It is highly recommended that large scale evaluation of thyroid hormone levels in Libyan CRF patients is performed more patients, especially elderly patients.

scholarly journals Changes in Thyroid Status During Perinatal Development of MCT8-Deficient Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (7) ◽  
pp. 2533-2541 ◽  
Author(s):  
Alfonso Massimiliano Ferrara ◽  
Xiao-Hui Liao ◽  
Pilar Gil-Ibáñez ◽  
Teresa Marcinkowski ◽  
Juan Bernal ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Gene Mutations ◽  
Perinatal Period ◽  
Deficiency Syndrome ◽  
Psychomotor Retardation ◽  
Relative Increase ◽  
Monocarboxylate Transporter ◽  
Adult Mice ◽  
Mct8 Deficiency ◽  
Deficient Mice

Abstract Patients with the monocarboxylate transporter 8 (MCT8) deficiency syndrome present with a severe psychomotor retardation and abnormal serum thyroid hormone (TH) levels, consisting of high T3 and low T4 and rT3. Mice deficient in Mct8 replicate the thyroid phenotype of patients with the MCT8 gene mutations. We analyzed the serum TH levels and action in the cerebral cortex and in the liver during the perinatal period of mice deficient in Mct8 to assess how the thyroid abnormalities of Mct8 deficiency develop and to study the thyroidal status of specific tissues. During perinatal life, the thyroid phenotype of Mct8-deficient mice is different from that of adult mice. They manifest hyperthyroxinemia at embryonic day 18 and postnatal day 0. This perinatal hyperthyroxinemia is accompanied by manifestations of TH excess as evidenced by a relative increase in the expression of genes positively regulated by T3 in both the cerebral cortex and liver. An increased tissue accumulation of T4 and T3 and the expression of TH alternative transporters, including Lat1, Lat2, Oatp1c1, and Oatp3a1 in the cortex and Lat2 and Oatp1b2 in the liver, suggested that Mct8 deficiency either directly interferes with tissue efflux of TH or indirectly activates other transporters to increase TH uptake. This report is the first to identify that the ontogenesis of TH abnormalities in Mct8-deficient mice manifests with TH excess in the perinatal period.

Hypermetabolism in Gaucher disease type I is not associated with altered thyroid hormone levels

2007 ◽  
Vol 30 (6) ◽  
pp. 985-985 ◽  
Author(s):  
M. Langeveld ◽  
E. Endert ◽  
W. M. Wiersinga ◽  
J. M. F. G. Aerts ◽  
C. E. M. Hollak
Keyword(s):  
Thyroid Hormone ◽  
Gaucher Disease ◽  
Disease Type ◽  
Type I ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Altered Thyroid
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