Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 4 , Pages 529-546 , December 2006

Syndromes of hormone resistance in the hypothalamic–pituitary–thyroid axis

  • Paolo Beck-Peccoz, MD (Professor of Endocrinology, University of Milan)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +39 2 50320606; Fax: +39 2 50320605.

References 

  1. Collu R, Tang J, Castagnè J, et al. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. The Journal of Clinical Endocrinology and Metabolism. 1997;82:1361–1365
  2. Bonomi M, Proverbio MC, Weber G, et al. Hyperplastic pituitary gland, high serum glycoprotein hormone α-subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSHβ gene. The Journal of Clinical Endocrinology and Metabolism. 2001;86:1600–1604
  3. Persani L, Ferretti E, Borgato S, et al. Circulating TSH bioactivity in sporadic central hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 2000;85:3631–3635
  4. Ferretti E, Persani L, Jaffrain-Rea ML, et al. Evaluation of the adequacy of l-T4 replacement therapy in patients with central hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 1999;84:924–929
  5. Shimon I, Cohen O, Lubetsky A, et al. Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism. Thyroid. 2002;12:823–827
  6. Stanbury JB, Rocmans P, Buhler UK, et al. Congenital hypothyroidism with impaired thyroid response to thyrotropin. The New England Journal of Medicine. 1968;21:1132–1136
  7. Sunthornthepvarakul T, Gottschalk ME, Hayashi Y, et al. Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. The New England Journal of Medicine. 1995;332:155–160
  8. de Roux N, Misrahi M, Brauner R, et al. Four families with loss of function mutations of the thyrotropin receptor. The Journal of Clinical Endocrinology and Metabolism. 1996;81:4229–4235
  9. Clifton-Bligh RJ, Gregory JW, Ludgate M, et al. Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. The Journal of Clinical Endocrinology and Metabolism. 1997;82:1094–1100
  10. Abramowicz MJ, Duprez L, Parma J, et al. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. The Journal of Clinical Investigation. 1997;99:3018–3024
  11. Biebermann H, Schöneberg T, Krude H, et al. Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 1997;82:3471–3480
  12. Gagné N, Parma J, Deal C, et al. Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities?. The Journal of Clinical Endocrinology and Metabolism. 1998;83:1771–1775
  13. Tiosano D, Pannain S, Vassart G, et al. The hypothyroidism in an inbred kindred with congenital thyroid hormone and glucocorticoid deficiency is due to a mutation producing a truncated thyrotropin receptor. Thyroid. 1999;9:887–894
  14. Tonacchera M, Agretti P, Pinchera A, et al. Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene. The Journal of Clinical Endocrinology and Metabolism. 2000;85:1001–1008
  15. Russo D, Betterle C, Arturi F, et al. A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH. The Journal of Clinical Endocrinology and Metabolism. 2000;85:4238–4242
  16. Nagashima T, Murakami M, Onigata K, et al. Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. Thyroid. 2001;11:551–559
  17. Tonacchera M, Agretti P, De Marco G, et al. Thyroid resistance to TSH complicated by autoimmune thyroiditis. The Journal of Clinical Endocrinology and Metabolism. 2001;86:4543–4546
  18. Bretones P, Duprez L, Parma J, et al. A familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene. Thyroid. 2001;11:977–980
  19. Alberti L, Proverbio MC, Costagliola S, et al. Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 2002;87:2549–2555
  20. Calaciura F, Motta RM, Miscio G, et al. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia. The Journal of Clinical Endocrinology and Metabolism. 2002;87:3209–3214
  21. Jordan N, Williams N, Gregory JW, et al. The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population. The Journal of Clinical Endocrinology and Metabolism. 2003;88:1002–1003
  22. Park SM, Clifton-Bligh RJ, Betts P, et al. Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor. Clinical Endocrinology. 2004;60:220–227
  23. Tonacchera M, Perri A, De Marco G, et al. Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 2004;89:5787–5793
  24. Richter-Unruh A, Hauffa BP, Pfarr N, et al. Congenital primary hypothyroidism in a Turkish family caused by a homozygous nonsense mutation (R609X) in the thyrotropin receptor gene. Thyroid. 2004;14:971–974
  25. Camilot M, Teofoli F, Gandini A, et al. Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygous. Clinical Endocrinology. 2005;63:146–151
  26. Fricke-Otto S, Pfarr N, Muhlenberg R, et al. Mild congenital primary hypothyroidism in a Turkish family caused by a homozygous missense thyrotropin receptor (TSHR) gene mutation (A593V). Experimental and Clinical Endocrinology & Diabetes. 2005;113:582–585
  27. Tsunekawa K, Onigata K, Morimura T, et al. Identification and functional analysis of novel inactivating thyrotropin receptor mutations in patients with thyrotropin resistance. Thyroid. 2006;16:471–479
  28. Refetoff S. Resistance to thyrotropin. Journal of Endocrinological Investigation. 2003;26:770–779
  29. Calebiro D, de Filippis T, Lucchi S, et al. Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Human Molecular Genetics. 2005;14:2991–3002
  30. Xie J, Pannain S, Pohlenz J, et al. Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH. The Journal of Clinical Endocrinology and Metabolism. 1997;82:3933–3940
  31. Nogueira CR, Nguyen LQ, Coelho-Neto JR, et al. Structural analysis of the thyrotropin receptor in four patients with congenital hypothyroidism due to thyroid hypoplasia. Thyroid. 1999;9:523–529
  32. Grasberger H, Vaxillaire M, Pannain S, et al. Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3-26.1. Human Genetics. 2005;7:1–8
  33. Mantovani G, Ballarè E, Giammona E, et al. The Gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. The Journal of Clinical Endocrinology and Metabolism. 2002;87:4736–4740
  34. Kopp P. Perspective: genetic defects in the etiology of congenital hypothyroidism. Endocrinology. 2002;143:2019–2024
  35. Vigone MC, Fugazzola L, Zamproni I, et al. persistent mild hypothyroidism associated with novel sequence variants of the DUOX2 gene in two siblings. Human Mutation. 2005;26:395
  36. Usala SJ, Bale AE, Gesundheit N, et al. Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbAβ gene. Molecular endocrinology (Baltimore, Md.). 1988;2:1217–1220
  37. Refetoff S, Weiss R, Usala S. The syndromes of resistance to thyroid hormone. Endocrine Reviews. 1993;14:348–399
  38. Jameson J. Mechanism by which thyroid hormone receptor mutations cause clinical syndromes of resistance to thyroid hormone. Thyroid. 1994;4:485–492
  39. Brucker-Davis F, Scarulis MC, Grace MB, et al. Genetic and clinical features in 42 kindreds with resistance to thyroid hormone. Annals of Internal Medicine. 1995;123:572–583
  40. Adams M, Matthews C, Collingwood TN, et al. Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the hormone receptor β gene. The Journal of Clinical Investigation. 1994;94:506–515
  41. Beck-Peccoz P, Chatterjee VKK. The variable clinical phenotype in thyroid hormone resistance syndrome. Thyroid. 1994;4:225–232
  42. Dumitrescu AM, Liao XH, Best TB, et al. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. American Journal of Human Genetics. 2004;74:168–175
  43. Friesema EC, Grueters A, Biebermann H, et al. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004;364:1435–1437
  44. Brockmann K, Dumitrescu AM, Best TT, et al. X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. Journal of Neurology. 2005;252:663–666
  45. Schwartz CE, May MM, Carpenter NJ, et al. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. American Journal of Human Genetics. 2005;77:41–53
  46. Maranduba CM, Friesema EC, Kok F, et al. Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. Journal of Medical Genetics. 2006;43:457–460
  47. Biebermann H, Ambrugger P, Tarnow P, et al. Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8. European Journal of Endocrinology. 2005;153:359–366
  48. Holden KR, Zuniga OF, May MM, et al. X-linked MCT8 gene mutations: characterization of the pediatric neurologic phenotype. Journal of Child Neurology. 2005;20:852–857
  49. Herzovich V, Vaiani E, Marino R, et al. Unexpected peripheral markers of thyroid function in a patient with a novel mutation of the MCT8 thyroid hormone transporter gene. Hormone Research. 2006;67:1–6
  50. Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nature Genetics. 2005;37:1247–1252
  51. Berry MJ. Insights into the hierarchy of selenium incorporation. Nature Genetics. 2005;37:1162–1163
  52. Gurnell M, Beck-Peccoz P, Chatterjee VKK. Resistance to thyroid hormone. In:  DeGroot LJ,  Jameson JL editor. Endocrinology. 5th edn.. Philadelphia: Elsevier Saunders; 2006;p. 2227–2237
  53. Takeda K, Sakurai A, DeGroot LJ, et al. Recessive inheritance of thyroid hormone resistance caused by complete deletion of the protein-coding region of the thyroid hormone receptor-β gene. The Journal of Clinical Endocrinology and Metabolism. 1992;74:49–55
  54. Yen PM, Chin WW. Molecular mechanism of dominant negative activity by nuclear hormone receptors. Molecular endocrinology (Baltimore, Md.). 1994;8:1450–1454
  55. Weiss RE, Xu J, Ning G, et al. Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. EMBO Journal. 1999;18:1900–1904
  56. Friesema EC, Ganguly S, Abdalla A, et al. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. The Journal of Biological Chemistry. 2003;278:40128–40135
  57. Schneider MJ, Fiering SN, Pallud , et al. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Molecular endocrinology (Baltimore, Md.). 2001;15:2137–2148
  58. Beck-Peccoz P, Mannavola D. Syndromes of resistance to thyroid hormone: clinical aspects. In:  Beck-Peccoz P editors. Syndromes of Hormone Resistance on the Hypothalamic-Pituitary-Thyroid Axis. Boston: Kluwer Academic Publishers; 2004;p. 69–88
  59. Geffner ME, Su F, Ross NS, et al. An argine to histidine mutation in codon 311of the c-erbA β gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype. The Journal of Clinical Investigation. 1993;91:538–546
  60. Beck-Peccoz P, Brucker-Davis F, Persani L, et al. Thyrotropin-secreting pituitary tumors. Endocrine Reviews. 1996;17:610–638
  61. Beck-Peccoz P, Piscitelli G, Cattaneo M, et al. Successful treatment of hyperthyroidism due to nonneoplastic pituitary TSH hypersecretion with 3, 5,3′-triiodothyroacetic acid (TRIAC). Journal of Endocrinological Investigation. 1983;6:217–223
  62. Hamon P, Bovier-Lapierre M, Robert M, et al. Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-Thyroxine therapy. The Journal of Clinical Endocrinology and Metabolism. 1988;67:1089–1093
  63. Crinò A, Borrelli P, Salvatori R, et al. Anti-iodothyronine autoantibodies in a girl with hyperthyroidism due to pituitary resistance to thyroid hormones. Journal of Endocrinological Investigation. 1992;15:113–120
  64. Takeda T, Suzuki S, Liu RT, et al. Triiodothyroacetic acid has unique potential for therapy of resistance to thyroid hormone. The Journal of Clinical Endocrinology and Metabolism. 1995;80:2033–2040

PII: S1521-690X(06)00085-6

doi: 10.1016/j.beem.2006.11.001

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 4 , Pages 529-546 , December 2006

Article Tools

* Image Usage & Resolution