Refetoff S, Weiss RE, Usala SJ.. The syndromes of resistance to thyroid hormone. Endocr Rev 14: 348-399

Department of Medicine, University of Chicago, Illinois 60637.
Endocrine Reviews (Impact Factor: 21.06). 07/1993; 14(3):348-99. DOI: 10.1210/edrv-14-3-348
Source: PubMed
8 Reads
  • Source
    • "Subclinical thyroid disease refers to the situation when increased (hypothyroidism) or decreased (hyperthyroidism) plasma TSH concentration is observed while free T4 and total T3 concentrations are in normal range [4]. Resistance to thyroid hormone (RTH) defines a syndrome in which tissues present reduced sensitivity to the action of TH [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Thyroid hormones (THs) are potent hormones modulating liver lipid homeostasis. The perturbation of lipid homeostasis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a very common liver disorder. It was reported that NAFLD patients were associated with higher incidence of hypothyroidism. However, whether abnormal thyroid function contributes to the pathogenesis of NAFLD remains unclear. Results We used in vivo models to investigate the influence of hypothyroidism and TH on hepatic lipid homeostasis. We did not observe hepatic triglyceride accumulation in the liver of hypothyroid mice, although the liver was enlarged. We then characterized the hepatic fatty acid composition with gas chromatography–mass spectrometry in mice under different thyroid states. We found that hypothyroidism decreased saturated fatty acid (SFA) content while TH treatment restored the level of SFA. In agreement with this finding, we observed that the expression of acetyl-CoA carboxylase 1 and fatty acid synthase, the rate-limit enzymes for de novo lipogenesis (DNL), decreased in hypothyroid mice while increased after TH treatment. We also found that the ratio of C18:1n-9/C18:0 and C16:1n-7/C16:0 was decreased by TH treatment, suggesting the activity of stearoyl-CoA desaturase-1 was suppressed. This finding indicated that TH is able to suppress triglyceride accumulation by reducing fatty acid desaturation. Additionally, we found that hepatic glycogen content was substantially influenced by TH status, which was associated with glycogen synthase expression. The increased glycogen storage might explain the enlarged liver we observed in hypothyroid mice. Conclusions Taken together, our study here suggested that hypothyroidism in mice might not lead to the development of NAFLD although the liver became enlarged. However, disturbed TH levels led to altered hepatic fatty acid composition and glycogen accumulation.
    Cell and Bioscience 07/2014; 4(1):38. DOI:10.1186/2045-3701-4-38 · 3.63 Impact Factor
  • Source
    • "Resistance to thyroid hormone (RTH) is a rare disorder characterized by reduced tissue response to free thyroxine (FT4) hormone. RTH is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,3′-l-triiodothyronine (T3), with persistent elevation of circulating free T3 (FT3) and FT4 levels, along with non-suppressed serum thyrotropin (TSH) [1,2]. Sporadic cases are common, but recessive cases are rare [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Resistance to thyroid hormone is a rare syndrome, where although the level of thyroid hormone is elevated, the level of thyroid stimulating hormone is not suppressed. The patient in our case report is, to the best of our knowledge, the first with this syndrome identified in Oman. In one Omani family, a 15-year-old girl of Arabian origin was pre-diagnosed with resistance to thyroid hormone. Blood sample was collected and DNA was isolated for molecular genetic testing. The results revealed a rare mutation A268G in the gene for thyroid hormone receptor beta.We believe that this mutation is the cause of the pathology in our patient. We report the presence of a rare mutation in the thyroid hormone receptor beta gene for the first time in the Omani population. Due to the rates of consanguinity being high among the Omani population, we are aiming to screen our patient's family members and provide genetic counseling.
    Journal of Medical Case Reports 01/2014; 8(1):12. DOI:10.1186/1752-1947-8-12
  • Source
    • "Impaired tyrosine sulfation of TSH receptor molecules by inactivation of TPST2 reduces responsiveness to TSH and causes the functional failure of the thyroid in grt mice [27]. Thyroid hormone (TH) functions in many critical aspects of brain development, including synaptic formation [22], neuronal migration [23], and glial myelination [24], and, consequently, TH deficiency causes mental retardation [25]. Interestingly hypothyroid rats display a decrease in the number of PV-positive interneurons [1], and this phenomenon is reversed by treatment with TH [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons.
    Neuroscience Letters 12/2013; 559. DOI:10.1016/j.neulet.2013.11.052 · 2.03 Impact Factor
Show more