S Refetoff

Summary

Affiliation: University of Chicago
Country: USA

Publications

  1. ncbi A mouse model of resistance to thyroid hormone produced by somatic gene transfer of a mutant thyroid hormone receptor
    Y Hayashi
    Department of Medicine, University of Chicago, Illinois 60637, USA
    Mol Endocrinol 10:100-6. 1996
  2. ncbi The syndrome of resistance to thyroid stimulating hormone
    Samuel Refetoff
    Department of Medicine, the Committees on Genetics and Molecular Medicine, J P Kennedy Jr Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637, USA
    J Chin Med Assoc 66:441-52. 2003
  3. ncbi A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone
    Joaquin Lado-Abeal
    University of Chicago, MC 3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 90:1760-7. 2005
  4. doi A novel monocarboxylate transporter 8 gene mutation as a cause of severe neonatal hypotonia and developmental delay
    Anastasios Papadimitriou
    Pediatric Endocrinology Unit, Third Department of Pediatrics, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Haidari, Athens 124 62, Greece
    Pediatrics 121:e199-202. 2008
  5. pmc Changes in thyroid status during perinatal development of MCT8-deficient male mice
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Endocrinology 154:2533-41. 2013
  6. pmc Coexistence of THRB and TBG gene mutations in a Turkish family
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    J Clin Endocrinol Metab 98:E1148-51. 2013
  7. pmc Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency
    Charles F Verge
    Department of Endocrinology, Sydney Children s Hospital, Randwick, NSW 2031, Australia
    J Clin Endocrinol Metab 97:4515-23. 2012
  8. pmc Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 97:1328-36. 2012
  9. ncbi Resistance to thyrotropin
    S Refetoff
    Department of Medicine, J P Kennedy Jr Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637, USA
    J Endocrinol Invest 26:770-9. 2003
  10. ncbi Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination
    Samuel Refetoff
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Best Pract Res Clin Endocrinol Metab 21:277-305. 2007

Research Grants

  1. THYROID PHYSIOLOGY STUDIES OF INHERITED DISORDERS
    Samuel Refetoff; Fiscal Year: 2005

Detail Information

Publications113 found, 100 shown here

  1. ncbi A mouse model of resistance to thyroid hormone produced by somatic gene transfer of a mutant thyroid hormone receptor
    Y Hayashi
    Department of Medicine, University of Chicago, Illinois 60637, USA
    Mol Endocrinol 10:100-6. 1996
    ..Transient somatic transfer of mutant TR genes provides a model for the study of RTH. It allows evaluation of the effect of genetic factors interacting with mutant TRs that modify the phenotype of RTH, without animal back-crossing...
  2. ncbi The syndrome of resistance to thyroid stimulating hormone
    Samuel Refetoff
    Department of Medicine, the Committees on Genetics and Molecular Medicine, J P Kennedy Jr Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637, USA
    J Chin Med Assoc 66:441-52. 2003
    ..A larger proportion of families express the phenotype of resistance to TSH in the absence of a TSHr defect. In many the inheritance is dominant and the genetic cause has not been yet determined...
  3. ncbi A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone
    Joaquin Lado-Abeal
    University of Chicago, MC 3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 90:1760-7. 2005
    ..Because the occurrence by chance is extremely unlikely, it is postulated that the presence of three guanines in the sequence created by the mutant nucleotide of the proposita results in a mutagenic site prone to de novo mutation...
  4. doi A novel monocarboxylate transporter 8 gene mutation as a cause of severe neonatal hypotonia and developmental delay
    Anastasios Papadimitriou
    Pediatric Endocrinology Unit, Third Department of Pediatrics, University of Athens School of Medicine, Attikon University Hospital, Rimini 1, Haidari, Athens 124 62, Greece
    Pediatrics 121:e199-202. 2008
    ..This case highlights the importance of determining thyroid hormone levels, especially triiodothyronine, in infants with severe neonatal hypotonia...
  5. pmc Changes in thyroid status during perinatal development of MCT8-deficient male mice
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Endocrinology 154:2533-41. 2013
    ..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...
  6. pmc Coexistence of THRB and TBG gene mutations in a Turkish family
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    J Clin Endocrinol Metab 98:E1148-51. 2013
    ..Our objective is to describe a family with the coexistence of resistance to thyroid hormone and thyroxine-binding globulin complete deficiency...
  7. pmc Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency
    Charles F Verge
    Department of Endocrinology, Sydney Children s Hospital, Randwick, NSW 2031, Australia
    J Clin Endocrinol Metab 97:4515-23. 2012
    ..In Mct8-deficient mice, the thyroid hormone analog, diiodothyropropionic acid (DITPA), does not require MCT8 to enter tissues and could be an effective alternative to thyroid hormone treatment in humans...
  8. pmc Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature
    Alfonso Massimiliano Ferrara
    Department of Medicine, The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 97:1328-36. 2012
    ..The most common cause of resistance to thyroid hormone (RTH) is heterozygous thyroid hormone receptor β (THRB) gene mutations. Homozygous mutations in the THRB gene are a rare event...
  9. ncbi Resistance to thyrotropin
    S Refetoff
    Department of Medicine, J P Kennedy Jr Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637, USA
    J Endocrinol Invest 26:770-9. 2003
    ..A larger proportion of families express the phenotype of resistance to TSH in the absence of a TSHr defect. In many the inheritance is dominant and the genetic cause has not been yet determined...
  10. ncbi Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination
    Samuel Refetoff
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Best Pract Res Clin Endocrinol Metab 21:277-305. 2007
    ....
  11. pmc Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site
    J Pohlenz
    Department of Medicine, Jr, Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637 1470, USA
    J Clin Invest 101:1028-35. 1998
    ..Thus, although the proposita is a compound heterozygote, because of the very low expression (< 2.5%) of one mutant allele, she is functionally hemizygous for an NIS without detectable bioactivity...
  12. pmc Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor alpha
    P E Macchia
    Department of Medicine, University of Chicago, MC 3090, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 98:349-54. 2001
    ..This is an in vivo demonstration that a TR deficiency can enhance sensitivity to TH. This effect is likely due to the abrogation of the constitutive "silencing" effect of TRalpha2 in tissues expressing the TRbeta isoforms...
  13. ncbi Sleep deprivation in the rat: IX. Recovery
    C A Everson
    Department of Psychiatry, University of Chicago, Illinois 60637
    Sleep 12:60-7. 1989
    ..Rebounds of high amplitude non-rapid eye movement (NREM) sleep occurred only in some rats and were smaller and less immediate...
  14. ncbi Thyroid function and effect of aging in combined hetero/homozygous mice deficient in thyroid hormone receptors alpha and beta genes
    R E Weiss
    Department of Medicine, Universty of Chicago, Chicago, Illinois 60637, USA
    J Endocrinol 172:177-85. 2002
    ....
  15. ncbi Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor beta-deficient mice
    R E Weiss
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Endocrinology 139:4945-52. 1998
    ..In contrast, except for HR and EE, the full manifestation of TH-mediated action required the presence of TR beta...
  16. ncbi Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant albumin (R218P) shows an apparent discrepancy between serum concentration and affinity for thyroxine
    S Pannain
    Department of Medicine, University of Chicago, Illinois 60637 1470, USA
    J Clin Endocrinol Metab 85:2786-92. 2000
    ....
  17. ncbi Resistance to thyroid hormone in subjects from two unrelated families is associated with a point mutation in the thyroid hormone receptor beta gene resulting in the replacement of the normal proline 453 with serine
    S Refetoff
    Department of Medicine, University of Chicago, Illinois 60637
    Thyroid 4:249-54. 1994
    ..Genetic studies indicate that the same mutation occurred independently in each of the two families...
  18. pmc Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone
    R E Weiss
    Department of Medicine, Jr Mental Retardation Research Center, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    EMBO J 18:1900-4. 1999
    ..It supports the hypothesis that a putative defect in the SRC-1 gene or another co-factor could be the cause of RTH in humans without mutations in the TR genes...
  19. ncbi A new family with hyperthyroxinemia caused by transthyretin Val109 misdiagnosed as thyrotoxicosis and resistance to thyroid hormone--a clinical research center study
    S Refetoff
    Department of Medicine, University of Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 81:3335-40. 1996
    ..These results are in agreement with the observations based on the crystallographic structure of TTR-Thr109 indicating that the extra atoms in Val as in Thr, which are absent in the Ala of the wild type TTR, widen the ligand binding site...
  20. ncbi A new point mutation (C446R) in the thyroid hormone receptor-beta gene of a family with resistance to thyroid hormone
    R E Weiss
    Department of Medicine, University of Chicago, Illinois 60637
    J Clin Endocrinol Metab 78:1253-6. 1994
    ..05). T3 at a concentration up to 100 nmol/L failed to enhance the transactivation of a reporter gene, and the mutant receptor inhibited the T3-mediated transcriptional activation of the wild-type TR beta...
  21. ncbi Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation
    Y Hayashi
    Department of Medicine, University of Chicago, Illinois 60637 1470
    Mol Endocrinol 7:1049-60. 1993
    ....
  22. ncbi Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping
    S Pannain
    Department of Medicine, University of Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 84:1061-71. 1999
    ..These results demonstrate the power of the DNA pooling strategy in the localization of a defective gene and the pitfalls of linkage analysis when 2 relatively rare mutations coexist in an inbred population...
  23. ncbi Thyrotropin regulation by thyroid hormone in thyroid hormone receptor beta-deficient mice
    R E Weiss
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Endocrinology 138:3624-9. 1997
    ..However, although TR alpha alone can mediate thyroid hormone induced TSH suppression, TR beta enhances the sensitivity of TSH down-regulation and may be essential for the complete suppression of TSH...
  24. ncbi Complete thyroxine-binding globulin (TBG) deficiency produced by a mutation in acceptor splice site causing frameshift and early termination of translation (TBG-Kankakee)
    G A Carvalho
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 83:3604-8. 1998
    ..This results in the insertion of a G in exon 2 and causes a frameshift and a premature stop at codon 195. This early termination of translation predicts a truncated TBG lacking 201 amino acids...
  25. ncbi Sleep deprivation in the rat: XIX. Effects of thyroxine administration
    B M Bergmann
    Department of Psychiatry, University of Chicago, Illinois 60637-1891, USA
    Sleep 18:317-24. 1995
    ..Thus, there is some doubt whether a general pathological catabolic process is the cause of death. It is also possible that a specific morbid process normally reversed by sleep was accelerated by T4 administration...
  26. ncbi Dominant inheritance of resistance to thyroid hormone not linked to defects in the thyroid hormone receptor alpha or beta genes may be due to a defective cofactor
    R E Weiss
    Department of Medicine, University of Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 81:4196-203. 1996
    ..An abnormal cofactor with a specific function in the regulation of thyroid hormone action is probably involved in the expression of the RTH phenotype in this family...
  27. ncbi Sleep deprivation in the rat: XI. The effect of guanethidine-induced sympathetic blockade on the sleep deprivation syndrome
    J J Pilcher
    Department of Psychiatry, University of Chicago, Illinois 60637
    Sleep 13:218-31. 1990
    ..Evidently, NE-mediated sympathetic activation was not critical to any of these effects, although a role for catecholamines cannot be ruled out...
  28. pmc Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families
    R E Weiss
    Department of Medicine, University of Chicago, Illinois 60637 1470
    J Clin Invest 91:2408-15. 1993
    ..Differences in clinical and laboratory findings in unrelated families harboring the same TR beta mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action...
  29. pmc In vivo interaction of steroid receptor coactivator (SRC)-1 and the activation function-2 domain of the thyroid hormone receptor (TR) beta in TRbeta E457A knock-in and SRC-1 knockout mice
    Manuela Alonso
    Department of Medicine, Committees on Genetics, The University of Chicago, Chicago, Illinois 60637, USA
    Endocrinology 150:3927-34. 2009
    ..This report demonstrates the dual interaction of NCoA in vivo: the TH-independent up-regulation possibly through another domain and TH-dependent down-regulation through the AF-2 domain...
  30. ncbi Resistance to thyroid hormone caused by a new mutation (V336M) in the thyroid hormone receptor beta gene
    J Pohlenz
    Department of Medicine, University of Chicago, Illinois, USA
    Thyroid 9:1001-4. 1999
    ....
  31. pmc Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion
    Caterina Di Cosmo
    Department of Medicine, University of Chicago, Chicago, Illinois, USA
    J Clin Invest 120:3377-88. 2010
    ..To our knowledge, this study is the first to demonstrate that Mct8 is involved in the secretion of TH from the thyroid gland and contributes, in part, to the low serum T4 level observed in MCT8-deficient patients...
  32. ncbi Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice
    Alexandra M Dumitrescu
    Department of Medicine, University of Chicago, MC 3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    Endocrinology 147:4036-43. 2006
    ..We conclude that cell-specific differences in intracellular TH content due to differences in contribution of the various TH transporters are responsible for the unusual clinical presentation of this defect, in contrast to TH deficiency...
  33. ncbi Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene
    J Pohlenz
    Department of Medicine, University of Chicago, Illinois 60637 1470, USA
    Biochem Biophys Res Commun 240:488-91. 1997
    ..While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterozygote (C272X) is sufficient to maintain active thyroidal I- uptake and function...
  34. ncbi Normal cellular uptake of thyroxine from serum of patients with familial dysalbuminemic hyperthyroxinemia or elevated thyroxine-binding globulin
    D H Sarne
    Department of Medicine, University of Chicago, Illinois 60637
    J Clin Endocrinol Metab 67:1166-70. 1988
    ..8 +/- 4.3 vs. 34.0 +/- 8.6 fmol/plate, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)..
  35. ncbi Complete deficiency of thyroxine-binding globulin (TBG-CD Buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene
    G A Carvalho
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Thyroid 8:161-5. 1998
    ..The latter is believed to be responsible for the TBG-CD either because the aberrant protein is not secreted or because of reduced abundance of its mRNA...
  36. ncbi Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor--a clinical research center study
    I M Rosenthal
    Department of Pediatrics, University of Chicago, Illinois 60637 1470, USA
    J Clin Endocrinol Metab 81:3802-6. 1996
    ..The results are compatible with relatively low constitutive activity associated with this structural abnormality of LHR...
  37. ncbi Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance to thyroid hormone
    Sunee Mamanasiri
    University of Chicago, MC 3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 91:3471-7. 2006
    ..In 23% of the families, TRbeta gene mutations occur de novo. Of the 141 families with RTH investigated by us, 21 (15%) had no TRbeta gene mutations detectable by sequencing from genomic DNA (gDNA) or cDNA (non-TR RTH)...
  38. ncbi Resistance to thyroid hormone in a patient with thyroid dysgenesis
    Helmut Grasberger
    Department of Medicine, University of Chicago, Chicago, Illinois, USA
    Thyroid 15:730-3. 2005
    ..To our knowledge, this represents the first report of congenital hypothyroidism secondary to thyroid dysgenesis complicated by coincidental RTH...
  39. ncbi A novel splice variant involving the 5' untranslated region of thyroid hormone receptor beta1 (TRbeta1)
    D Mannavola
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Endocrinol Invest 27:318-22. 2004
    ..Furthermore, the expression level in fibroblasts from patients with resistance to thyroid hormone with or without TRbeta gene mutations was not different to that in fibroblasts from normal controls...
  40. ncbi An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families
    T Sunthornthepvarakul
    Department of Medicine, University of Chicago, IL 60637
    Biochem Biophys Res Commun 202:781-7. 1994
    ..In every individual with FDH, the mutation was associated with the Sac I+ polymorphism in the albumin gene, strongly suggesting a founder effect...
  41. ncbi Three novel mutations causing complete T(4)-binding globulin deficiency
    S Reutrakul
    Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    J Clin Endocrinol Metab 86:5039-44. 2001
    ..This explains the lack of T(4)-binding globulin in the hemizygous affected subjects...
  42. ncbi Dominant role of thyrotropin-releasing hormone in the hypothalamic-pituitary-thyroid axis
    Amisra A Nikrodhanond
    Department of Medicine and the Committee on Molecular Metabolism and Nutrition, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 281:5000-7. 2006
    ..Thus, TRH is absolutely required for both TSH and TH synthesis but is not necessary for thyrotroph cell development...
  43. ncbi A novel thyroid hormone receptor-beta mutation that fails to bind nuclear receptor corepressor in a patient as an apparent cause of severe, predominantly pituitary resistance to thyroid hormone
    Sharon Y Wu
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Mail Code 3090, Chicago, Illinois 60645, USA
    J Clin Endocrinol Metab 91:1887-95. 2006
    ..Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone (TH)...
  44. pmc A thyroid hormone analog with reduced dependence on the monocarboxylate transporter 8 for tissue transport
    Caterina Di Cosmo
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Endocrinology 150:4450-8. 2009
    ..The potential clinical utility of this analog to patients with MCT8 mutations requires further studies...
  45. ncbi Mutations in SECISBP2 result in abnormal thyroid hormone metabolism
    Alexandra M Dumitrescu
    Department of Human Genetics, University of Chicago, MC 3090, 5841 S Maryland Ave, Chicago, Illinois 60637, USA
    Nat Genet 37:1247-52. 2005
    ..Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype...
  46. ncbi Effects of maternal levels of thyroid hormone (TH) on the hypothalamus-pituitary-thyroid set point: studies in TH receptor beta knockout mice
    Manuela Alonso
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Endocrinology 148:5305-12. 2007
    ..Thus, TH exposure in utero has an effect on the regulatory set point of the hypothalamus-pituitary-thyroid axis, which can be seen early in life and persists into adulthood...
  47. ncbi Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene (P453T)
    Sharon Y Wu
    Department of Medicine, The University of Chicago, Chicago, Illinois 60645, USA
    J Lab Clin Med 146:85-94. 2005
    ..We demonstrate that RTH patients can be evaluated either on or off thyroid hormone and still be distinguished from hypothyroid subjects without RTH...
  48. ncbi Hypothyroidism in thyroid transcription factor 1 haploinsufficiency is caused by reduced expression of the thyroid-stimulating hormone receptor
    Lars C Moeller
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Endocrinol 17:2295-302. 2003
    ..However, administration of a larger amount of TSH obliterates the response differences by saturating a reduced amount of receptor...
  49. ncbi RXR receptor agonist suppression of thyroid function: central effects in the absence of thyroid hormone receptor
    Paolo E Macchia
    Department of Medicine, Committee on Genetics and the J P Kennedy Jr Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637 1470, USA
    Am J Physiol Endocrinol Metab 283:E326-31. 2002
    ..The results suggest that a high-affinity RXR agonist with antihyperglycemic activity can cause central hypothyroidism independently of TR beta, the main mediator of hormone-induced TSH suppression...
  50. ncbi Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene
    T Sunthornthepvarakui
    Department of Medicine, University of Chicago, IL 60637
    N Engl J Med 332:155-60. 1995
  51. pmc Approach to the patient with resistance to thyroid hormone and pregnancy
    Roy E Weiss
    Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 3090, Chicago, IL 606037, USA
    J Clin Endocrinol Metab 95:3094-102. 2010
    ..If the TRbeta mutation is known in the mother, the fetus can be rapidly genotyped from DNA from amniocentesis for the same mutation, and then management decisions could be made regarding thyroid or antithyroid hormone treatment...
  52. pmc Autoimmunity in patients with resistance to thyroid hormone
    Marla S Barkoff
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    J Clin Endocrinol Metab 95:3189-93. 2010
    ..It was recently proposed that chronic TSH stimulation in RTH may induce an autoimmune response, thereby increasing the chance of their coexistence...
  53. pmc The syndrome of inherited partial SBP2 deficiency in humans
    Alexandra M Dumitrescu
    Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA
    Antioxid Redox Signal 12:905-20. 2010
    ..In this review we discuss the clinical presentation of SBP2 mutations, their effect on protein function, consequence for selenoproteins, and the clinical course of subjects with SBP2 defects...
  54. pmc Negative regulation by thyroid hormone receptor requires an intact coactivator-binding surface
    Tania M Ortiga-Carvalho
    Department of Medicine and Committee on Molecular Metabolism and Nutrition, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA
    J Clin Invest 115:2517-23. 2005
    ..Therefore, the AF-2 domain of TR-beta is required for positive and, paradoxically, for negative regulation by TH in vivo...
  55. pmc Clinical and molecular characterization of a novel selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X)
    Caterina Di Cosmo
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, U SA
    J Clin Endocrinol Metab 94:4003-9. 2009
    ..Although acquired abnormalities of thyroid hormone metabolism are common, inherited defects in humans involving the synthesis of selenoproteins, including iodothyronine deiodinases, have been described in only one recent publication...
  56. pmc Identification of a functional polymorphism of the human type 5 17beta-hydroxysteroid dehydrogenase gene associated with polycystic ovary syndrome
    Kenan Qin
    Department of Pediatrics, Section of Pediatric Endocrinology, The University of Chicago, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 91:270-6. 2006
    ..Type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5) appears to be the major testosterone-forming 17beta-HSD isoenzyme in females...
  57. ncbi Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent
    Helmut Grasberger
    Department of Medicine, University of Chicago, Illinois 60637, USA
    J Biol Chem 281:18269-72. 2006
    ..The identification of DUOXA genes has important implications for studies of the molecular mechanisms controlling DUOX expression and the molecular genetics of congenital hypothyroidism...
  58. ncbi Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: evidence for haploinsufficiency
    Roy E Weiss
    Department of Medicine, University of Chicago, Chicago, Illinois 60037, USA
    Endocrinology 143:1554-7. 2002
    ..This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2...
  59. ncbi Missense mutations of dual oxidase 2 (DUOX2) implicated in congenital hypothyroidism have impaired trafficking in cells reconstituted with DUOX2 maturation factor
    Helmut Grasberger
    Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    Mol Endocrinol 21:1408-21. 2007
    ..Rather, DUOXA2 allows rapid ER exit of folded DUOX2 or enhanced degradation of mutant DUOX2 proteins not competent for ER exit. DUOXA2 may thus be part of a secondary quality control system specific for DUOX2...
  60. ncbi A familial thyrotropin (TSH) receptor mutation provides in vivo evidence that the inositol phosphates/Ca2+ cascade mediates TSH action on thyroid hormone synthesis
    Helmut Grasberger
    Departments of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 92:2816-20. 2007
    ..Biallelic TSHR loss-of-function mutations cause resistance to TSH, clinically characterized by hyperthyrotropinemia, and normal or reduced thyroid gland volume, thyroid hormone output, and iodine uptake...
  61. ncbi Pituitary-thyroid setpoint and thyrotropin receptor expression in consomic rats
    Lars C Moeller
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Endocrinology 148:4727-33. 2007
    ..These strains of rat provide a model to study the cis- and trans-acting factors underlying the difference in TSHR expression...
  62. ncbi Multiple endocrine neoplasia 2A syndrome presenting as peripartum cardiomyopathy due to catecholamine excess
    Jaime Kim
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Eur J Endocrinol 151:771-7. 2004
    ..In summary, we report a case of multiple endocrine neoplasia 2A presenting as peripartum cardiomyopathy and cardiovascular collapse. Pheochromocytoma should be considered as a potential cause of peripartum cardiomyopathy...
  63. pmc Thyroid hormone receptor α and regulation of type 3 deiodinase
    Olga Barca-Mayo
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Endocrinol 25:575-83. 2011
    ..We conclude that the absence of TRα results in decreased clearance of TH by D3 and contributes to the TH hypersensitivity...
  64. ncbi Complete thyroxine-binding globulin (TBG) deficiency in two families without mutations in coding or promoter regions of the TBG genes: in vitro demonstration of exon skipping
    Sirimon Reutrakul
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 87:1045-51. 2002
    ..The cause of TBG deficiency in this family remains unknown...
  65. ncbi Sleep deprivation in the rat: V. Energy use and mediation
    B M Bergmann
    Department of Psychiatry, University of Chicago, Illinois 60637
    Sleep 12:31-41. 1989
    ..Results appear to rule out the first as a mediator. Evidence for the other two was equivocal...
  66. pmc Inherited defects of thyroid hormone metabolism
    A M Dumitrescu
    Department of Medicine, University of Chicago Medical Center, Chicago, IL, 60637, USA
    Ann Endocrinol (Paris) 72:95-8. 2011
    ..Here we summarize the clinical presentation of SBP2 mutations, their effect on SBP2 function and downstream consequences for selenoprotein synthesis and function...
  67. ncbi Repulsive separation of the cytoplasmic ends of transmembrane helices 3 and 6 is linked to receptor activation in a novel thyrotropin receptor mutant (M626I)
    Usanee Ringkananont
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Endocrinol 20:893-903. 2006
    ..Thus, repulsive separation of the juxtacytoplasmic TM6 and TM3 in the M626I model conclusively demonstrates a direct link between the opening of this cytoplasmic face of the receptor structure and G protein coupling...
  68. ncbi Novel biological and clinical aspects of thyroid hormone metabolism
    Alexandra M Dumitrescu
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Endocr Dev 10:127-39. 2007
    ..Opposite thyroid test abnormalities are found in mutations of the TH transporter MCT8, and appear to be caused by the resulting increases in D2 and D1 activities...
  69. pmc Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta
    A Sakurai
    Thyroid Study Unit, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 86:8977-81. 1989
    ..Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule...
  70. ncbi Resistance to thyroid hormone with and without receptor gene mutations
    S Refetoff
    Department of Medicine, the Committee on genetics, The University of Chicago, Chicago, Illinois, USA
    Ann Endocrinol (Paris) 64:23-5. 2003
  71. ncbi The effect of short-term treatment with recombinant human thyroid-stimulating hormones on leydig cell function in men
    Joaquin Lado-Abeal
    Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, USA
    Thyroid 13:649-52. 2003
    ..In conclusion, short-term elevations in serum TSH levels in the range reported in hypothyroid boys with precocious puberty did not increase serum testosterone levels in adult men...
  72. pmc Thyroid hormone action in the absence of thyroid hormone receptor DNA-binding in vivo
    Nobuyuki Shibusawa
    Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC1027, Chicago, Illinois 60637, USA
    J Clin Invest 112:588-97. 2003
    ..Inner ear development, although not completely normal, can occur in the absence of TR DNA-binding, suggesting that an alternative and perhaps novel thyroid hormone-signaling pathway may mediate these effects...
  73. ncbi Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity
    Helmut Grasberger
    The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Mol Endocrinol 19:1779-91. 2005
    ....
  74. ncbi Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci
    Helmut Grasberger
    Department of Medicine, The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 90:4025-34. 2005
    ..OBJECTIVE, SETTING, AND PARTICIPANTS: Toward the identification of novel RTSH genes, we studied five large, unrelated families comprising 102 individuals, 56 of whom were affected...
  75. ncbi Thyroid hormone responsive genes in cultured human fibroblasts
    Lars C Moeller
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 90:936-43. 2005
    ..This first systematic study of TH-mediated gene expression in normal human cells identifies several new TH-responsive genes and demonstrates that skin fibroblasts are suitable for the study of TH action in health and disease...
  76. ncbi Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3-26.1
    Helmut Grasberger
    Department of Medicine, The University of Chicago, 5841 S Maryland Avenue, MC3090, Chicago, IL, 60637, USA
    Hum Genet 118:348-55. 2005
    ..Fine mapping of key recombinants in the largest family localized the causative gene within a 3 cM/2.9 Mb interval. Thus, we report the first locus for congenital nongoitrous hypothyroidism identified by a genome wide screening approach...
  77. pmc A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene
    Alexandra M Dumitrescu
    Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA
    Am J Hum Genet 74:168-75. 2004
    ..Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter...
  78. ncbi Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks
    M R Waltz
    Department of Medicine, University of Chicago, IL 60637
    J Endocrinol Invest 13:343-9. 1990
    ..Whether the TBG-S phenotype observed in populations from the Pacific Islands is caused by the same mutation remains to be determined...
  79. pmc Distinct roles of deiodinases on the phenotype of Mct8 defect: a comparison of eight different mouse genotypes
    Xiao Hui Liao
    Department of Medicine, The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
    Endocrinology 152:1180-91. 2011
    ....
  80. ncbi Complete thyroxine-binding globulin (TBG) deficiency caused by a single nucleotide deletion in the TBG gene
    P Li
    Departments of Medicine and Pediatrics, University of Chicago, IL 60637
    Metabolism 40:1231-4. 1991
    ..The mutant allele correlated with the results of TBG analysis in serum. This defect was not present in affected subjects of any of seven unrelated families with complete TBG deficiency tested...
  81. pmc The coexistence of a novel inactivating mutant thyrotropin receptor allele with two thyroid peroxidase mutations: a genotype-phenotype correlation
    Chutintorn Sriphrapradang
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Clin Endocrinol Metab 96:E1001-6. 2011
    ..TSH receptor (TSHR) and thyroid peroxidase (TPO) gene mutations occur independently. This is the first report of their coexistence in the same individuals...
  82. ncbi Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance
    Sirimon Reutrakul
    The J P Kennedy Jr Mental Retardation Research Center, University of Chicago, Illinois 60637, USA
    Thyroid 14:311-9. 2004
    ..In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects...
  83. pmc Comparison of thyroidectomized calf serum and stripped serum for the study of thyroid hormone action in human skin fibroblasts in vitro
    Lars C Moeller
    Department of Medicine, University of Chicago, Chicago, Illinois 60645, USA
    Thyroid 19:639-44. 2009
    ..We therefore compared the use of TH-depleted medium, either by resin treatment (stripped-CS) or by the use of CS from a thyroidectomized calf (TxCS) for gene expression studies...
  84. ncbi Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes
    Lars C Moeller
    The University of Chicago, MC3090, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Mol Endocrinol 19:2955-63. 2005
    ....
  85. ncbi Resistance to thyroid hormone: one of several defects causing reduced sensitivity to thyroid hormone
    Samuel Refetoff
    Nat Clin Pract Endocrinol Metab 4:1. 2008
  86. pmc Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism
    Ilaria Zamproni
    Laboratory of Pediatric Endocrinology, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
    J Clin Endocrinol Metab 93:605-10. 2008
    ..DUOX2 deficiency produces congenital hypothyroidism (CH) in humans and mice. We recently cloned a novel gene, the product of which (dual oxidase maturation factor 2; DUOXA2) is required to express DUOX2 enzymatic activity...
  87. ncbi Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxidase (TPO) gene in Israelis
    Yardena Tenenbaum-Rakover
    Paediatric Endocrine Unit, Ha Emek Medical Centre, Afula, Israel
    Clin Endocrinol (Oxf) 66:695-702. 2007
    ..The objectives of this study were to characterize the molecular basis of IOD in an Israeli Arab-Muslim population and to analyse the clinical, neurological and imaging data of patients with TPO mutations followed for up to 29 years...
  88. pmc Pendred syndrome in two Galician families: insights into clinical phenotypes through cellular, genetic, and molecular studies
    Fernando Palos
    Unidade de Enfermedades Tiroideas e Metabolicas, Department of Medicine, University of Santiago de Compostela, C San Francisco sn, Santiago de Compostela 15705, Spain
    J Clin Endocrinol Metab 93:267-77. 2008
    ..In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter...
  89. pmc A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism
    J H Duncan Bassett
    Molecular Endocrinology Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London, United Kingdom
    Mol Endocrinol 22:501-12. 2008
    ..Furthermore, TSH did not affect the differentiation or function of osteoblasts or osteoclasts in vitro. These data indicate the hypothalamic-pituitary-thyroid axis regulates skeletal development via the actions of T(3)...
  90. ncbi Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis
    Arturo Hernandez
    Dartmouth Medical School, Lebanon, NH 03756, USA
    Endocrinology 148:5680-7. 2007
    ..In conclusion, the absence of D3 activity results in impaired clearance of T(3) and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid...
  91. ncbi A new case of resistance to thyroid hormone caused by a de novo P453T mutation in the thyroid hormone receptor gene in an Israeli child
    Avraham Ishay
    Thyroid 13:409-12. 2003
  92. ncbi Delineation of the discontinuous-conformational epitope of a monoclonal antibody displaying full in vitro and in vivo thyrotropin activity
    Sabine Costagliola
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, ULB, 808 Lennik Street, B 1070 Brussels, Belgium
    Mol Endocrinol 18:3020-34. 2004
    ..Delineation of the conformational epitopes of these stimulating antibodies opens the way to the identification of the molecular mechanisms implicated in the activation of the TSHr...
  93. ncbi Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect
    Guntram Borck
    Children s Hospital of the Johannes Gutenberg University, Mainz, Germany
    J Clin Endocrinol Metab 89:4136-41. 2004
    ....
  94. pmc Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release
    Simonetta Lisi
    Department of Endocrinology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
    Proc Natl Acad Sci U S A 100:14858-63. 2003
    ..Our study points to a major role of megalin in thyroid homeostasis with possible implications in thyroid diseases...
  95. ncbi Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide
    Anja Fingerhut
    Department of Medicine, University of Essen, 45122 Essen, Germany
    J Clin Endocrinol Metab 89:2477-83. 2004
    ..This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency...
  96. ncbi Regression of a large goiter in a patient with resistance to thyroid hormone by every other day treatment with triiodothyronine
    João Anselmo
    Unit of Endocrinology, Hospital Divino Espirito Santo, Ponta Delgada, Portugal
    Thyroid 14:71-4. 2004
    ..The required dose of 250 microg suppressing TSH to values below 0.1 mU/L was derived by titration. Supraphysiological doses of L-T3 can be given safely as long-term treatment of goiter in patients RTH...
  97. ncbi Analysis of the PAX8 gene in congenital hypothyroidism caused by different forms of thyroid dysgenesis in a father and daughter
    Abdullah Bereket
    Department of Pediatrics, Division of Pediatric Endocrinology, Marmara University, Istanbul, Turkey
    J Pediatr Endocrinol Metab 17:1021-9. 2004
    ..The involvement of the candidate gene, PAX8, as the cause of thyroid dysgenesis in this family was partially excluded by linkage analysis, and the possibility of a de novo mutation excluded by sequencing...
  98. ncbi Unique regulation of thyroid hormone metabolism during fasting in the house musk shrew (Suncus murinus, Insectivora: Soricidae)
    Yoko Takeuchi
    Department of Teratology and Genetics, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464 8601, Japan
    Gen Comp Endocrinol 146:236-41. 2006
    ..The increased T3/T4 ratio together with increased D2 activity in BAT and cerebral cortex with fasting suggest that D2 rather than D1 is responsible for the maintenance of T3 levels in the house musk shrew...
  99. ncbi Type 1 iodothyronine deiodinase in the house musk shrew (Suncus murinus, Insectivora: Soricidae): cloning and characterization of complementary DNA, unique tissue distribution and regulation by T(3)
    Margarita Rogatcheva
    Department of Teratology and Genetics, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Japan
    Gen Comp Endocrinol 127:48-58. 2002
    ..These results suggest that D2 contributes to the production and maintenance of T(3) levels in the house musk shrew...
  100. ncbi Steroid receptor coactivator-1 deficiency causes variable alterations in the modulation of T(3)-regulated transcription of genes in vivo
    Yoko Takeuchi
    Research Institute of Environmental Medicine, Nagoya University, Nagoya 464 8601, Japan
    Endocrinology 143:1346-52. 2002
    ..SRC-1 appears to be involved not only in transcriptional activation by liganded TRs, but also in the suppression by liganded or unliganded TRs. Some of the effects of SRC-1 may be TR isoform specific...

Research Grants1

  1. THYROID PHYSIOLOGY STUDIES OF INHERITED DISORDERS
    Samuel Refetoff; Fiscal Year: 2005
    ..The possibility for a gain-of-function mutation in the H202 generating-THOX gene will be explored, based on its selection for iodide retention in the heterozygous state that could cause gland destruction in homozygotes. ..