Buscar en
Endocrinología y Nutrición
Toda la web
Inicio Endocrinología y Nutrición Fisiopatología del hipotiroidismo congénito primario
Información de la revista
Vol. 52. Núm. 8.
Páginas 431-445 (Octubre 2005)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 52. Núm. 8.
Páginas 431-445 (Octubre 2005)
Revisiones
Acceso a texto completo
Fisiopatología del hipotiroidismo congénito primario
Physiopathology of primary congenital hypothyroidism
Visitas
...
E. Vicens-Calvet??
Autor para correspondencia
evicens@vodafone.es

Correspondencia: Dr. E. Vicens-Calvet. Unidad de Endocrinología. Hospital Materno-Infantil Vall d’Hebron. Pg. Vall d’Hebron, 119-129. 08035 Barcelona. España.
, M. Clemente, A. Carreño
Unidad de Endocrinología. Hospital Materno-Infantil. Vall d’Hebron. Barcelona. España
Información del artículo

El pronóstico del hipotiroidismo congénito ha cambiado radicalmente desde la instauración en la mayoría de países de las unidades de cribado precoz y seguimiento de esta endocrinopatía. Sin embargo, sus factores etiológicos aún son poco conocidos.

En el hipotiroidismo congénito transitorio, las causas principales son, durante el parto, la sobrecarga yodada que puede experimentar el feto por pincelaciones antisépticas con povidona yodada y la vía materna, y en el período de recién nacido (fenómeno de Wolf-Chaikoff), la inmadurez del sistema hipotálamo-hipofisario que condiciona una deficiencia de funcionalismo del tiroides del prematuro, más aun si se trata de un prematuro patológico, y una relativa deficiencia de yodo en las fórmulas de la leche.

En el hipotiroidismo congénito definitivo las principales etiologías son las mutaciones que ocurren en los factores de transcripción y en el complejo enzimático preciso para la formación de hormonas tiroideas (dishormonogénesis).

Hoy se conocen una serie de factores de transcripción: FOXE I (TITF 2), NK X2.1 (TITF 1), PAX 8 y Shh (en ratones) cuyas mutaciones son causa de las disgenesias tiroideas, aunque expliquen sólo un pequeño porcentaje de ellas.

Dentro de las dishormonogénesis están bien estudiadas las mutaciones de la mayoría de los trastornos enzimáticos que ocurren tanto en el borde basocelular como en el apical del tirocito, y que ocasionan un hipotiroidismo congénito con glándula normosituada.

El hipotiroidismo congénito definitivo ha pasado de ser considerado como una simple embriopatía o malformación a una entidad de gran interés en los estudios de biología molecular para conocer el entramado de genes que son precisos para el normal funcionamiento de la glándula.

Palabras clave:
Hipotiroidismo congénito
Potiroidismo congénito transitorio
Hipotiroidismo congénito definitivo
Dishormonogénesis

In most countries the prognosis of congenital hypothyroidism (CH) has changed dramatically since the introduction of units for the early screening and follow-up of this endocrine disorder.

However, the etiological factors involved have not yet been well characterized.

In transitory CH the main causes are iodine overload in the fetus due to antiseptic brushing with povidone-iodine, maternal transfer during delivery and in the neonatal period (the Wolf-Chaikoff effect), immaturity of the hypothalamus-pituitary system leading to thyroid function deficiency in premature infants, especially if abnormalities are present, and a relative deficiency of iodine in formula milk.

In definitive CH the main etiological factors are mutations in transcription factors and in the enzyme complex required for the formation of thyroid hormones (dyshormonogenesis). Currently, a series of transcription factors are known – FOXE I (TITF 2), NK X2.1 (TITF 1), PAX 8 and Shh (in mice) – whose mutations give rise to thyroid dysgenesis, although these mutations explain only a small percentage of them. Within dyshormonogenesis, mutations of most of the enzyme disorders that occur both in the basal and apical borders of thyroid cells and that cause CH in normally located glands are well known.

Definitive CH is no longer considered a simple embryo disorder or malformation and is currently of great interest in molecular biology to determine the network of genes required for normal thyroid function.

Key words:
Congenital hypothyroidism
Transitory congenital hypothyroidism
Definitive congenital hypothyroidism
Dyshormonogenesis
El Texto completo está disponible en PDF
Bibliografía
[1.]
E. Vicens-Calvet, M. Bargadá.
Cribado, diagnóstico definitivo y seguimiento del hipotiroidismo congénito.
Endocrinol Nutr, 49 (2002), pp. 84-87
[2.]
J.C. Moreno.
Fundamentos moleculares del hipotiroidismo congénito.
An Pediatr, 60 (2004), pp. 36-41
[3.]
J. Wolf, I.L. Chaikoff, R.C. Goldberg, J.R. Meier.
The temporary nature of the inhibitory action of excess iodide on organic iodine synthesis in the normal thyroid.
Endocrinology, 45 (1949), pp. 504-513
[4.]
P.H.K. Eng, G.R. Cardona, S.-H. Fang, M. Previti, S. Alex, N. Carrasco, et al.
Escape from the acute Wolff.-Chaikoff effects is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid protein.
Endocrinology, 140 (1999), pp. 3404-3410
[5.]
C. Spitzweg, J.C. Morris.
The sodium iodide symporter: its pathophysiological and therapeutic implications.
Clin Endocrinol (Oxf), 57 (2002), pp. 559-574
[6.]
O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, et al.
The sodium/iodide symporter (NIS): characterization, regulation and medical significance.
Endocrine Rev, 24 (2003), pp. 48-77
[7.]
J. Pohlenz, L. Duprez, R.E. Weiss, G. Vassart, S. Refetoff, S. Costagliola.
Failure of membrane targeting causes the functional defect of two mutant sodium iodide sympoter.
J Clin Endocrinol Metab, 85 (2000), pp. 2366-2369
[8.]
J.P. Chabrolle, A. Rossier.
Goiter an hypothyroidism in the newborn after cutaneous absortion of iodine.
Arch Dis Child, 53 (1978), pp. 495-498
[9.]
E. Vicens-Calvet, M.A. Albisu.
Iatrogènia per povidona iodada.
Pediatria Catalana, 58 (1998), pp. 312-314
[10.]
C.M. Gordon, H. David, D.H. Rowitch, M.L. Mitchell, I.S. Kohane.
Topical iodine and neonatal hypothyroidism.
Arch Pediatr Adolesc Med, 149 (1995), pp. 1339
[11.]
J. Arena, I. Eguileor, J. Emparanza.
Repercusión sobre la función tiroidea del RN a término de la aplicación de povidona iodada en el muñón umbilical.
An Esp Pediatr, 23 (1985), pp. 562-568
[12.]
J. Arena Ansotegui, J.I. Emparanza Knörr, M.J. San Millan Vege, A. Garrido Chercoles, I. Eguileor Gurtubai.
Sobrecarga yodada al recién nacido por utilizar PVP-iodada para la preparación perineal materna en el parto vaginal.
An Esp Pediatr, 30 (1989), pp. 23-26
[13.]
P. Chun, W. Chen, K.W. Wu.
Povidone-iodine in umbilical cord care interferes with neonatal screening for hypothyroidism.
Eur J Pediatrics, 153 (1994), pp. 756-758
[14.]
J.P. Chamoine, M. Boulvain, P. Bourdoux, A. Pardou, H.V. Van Thi, A.M. Ermans, et al.
Increased recall rate at screening for congenital hypothyroidism in breast fed infants born to iodine overload mothers.
Arch Dis Child, 63 (1988), pp. 1207-1210
[15.]
G. Bodegard, K. Fyrö, A. Larssom.
Psycological reactions in 102 families with a newborn who has falsely positive screening test for congenital hypothyroidism.
Acta Paediatr Scand, (1983), pp. 1-21
[16.]
R.D. Mainwaring, J.J. Lamberti, G.F. Billman, J.C. Nelson.
Suppression of the pituitary thyroid axis after cardiopulmonary bypass in the neonate.
Ann Thorac Surg, 58 (1994), pp. 1078-1082
[17.]
T.V. Brogan, S.L. Bratton, A.M. Lynn.
Thyroid function in infants following cardiac surgery: comparative effects of iodinated and noniodinated topical antiseptics.
Crit Care Med, 25 (1997), pp. 1583-1587
[18.]
M. Bettendorf, K.G. Schmidt, U. Tiefenbacher, J. Grulich-Henn, U.E. Heinrich, D.K. Shönberg.
Transient secondary hypothyroidism in children after cardiac surgery.
Pediatr Res, 41 (1997), pp. 375-379
[19.]
N. Linder, B. Sela, B. German, N. Davidovitch, J. Kuint, J. Hegesh, et al.
Iodine an hypothyroidism in neonates with congenital hearth disease.
Arch Dis Child Fetal Neonatal Ed, 77 (1997), pp. F239-F240
[20.]
M. Bettendorf, K.G. Schmidt, J. Grulich-Henn, H.E. Ulmer, U.E. Heinrich.
Tri-odothyronine treatment in children after cardiac surgery: a double-blind. randomised placebo-controlled study.
[21.]
M.J. Cero Martín, A. Fernández Ruiz, L. García-Guereta, F. Benito Bartolomé, M.D. Rubio Vidal, S. Ares Segura, et al.
Alteraciones en la función tiroidea en niños con cardiopatía congénita tras la realización del cateterismo con contrastes yodados.
Rev Esp Cardiol, 53 (2000), pp. 517-524
[22.]
Document de Consens sobre utilització d’antiseptics en l’etapa perinatològica. Barcelona: Publicacions de la Direcció General de Salut Pública. Generalitat de Catalunya; 1998.
[23.]
E. Vicens-Calvet, N. Potau, E. Carreras, J. Bellart, M.A. Albisu, A. Carrascosa.
Diagnosis and treatment in utero of goiter with hypothyroidism caused by iodide overload.
J Pediatr, 133 (1998), pp. 147-148
[24.]
Ruiz-Cuevas P. Estudio de la función hipotálamo-hipofisariotiroidea en recién nacidos prematuros de 30-36 semanas de gestación [tesis doctoral]. Barcelona: Universidad Autónoma de Barcelona; 2003.
[25.]
Clemente M. Estudio de la función hipotálamo-hipofisario-tiroidea en 117 recién nacidos pretérmino de menos de 30 semanas de edad gestacional [tesis doctoral]. Barcelona: Universidad Autónoma de Barcelona; 2003.
[26.]
N. Linder, N. Davidovitch, B. Reichman, J. Kuint, D. Lubin, J. Meyerovitch, et al.
Topical iodine-containing antiseptics and subclinical hypothyroidism in preterm infants.
J Pediatr, 131 (1997), pp. 434-439
[27.]
G. Weber, M.C. Vigone, A. Rapa, G. Bona, G. Chiumello.
Neonatal transient hypothyroidism: aetiological study.
Arch Dis Child Fetal Neonatal Ed, 79 (1998), pp. F70-F72
[28.]
D.A. Fisher.
The hypothyroxinemia of prematurity [editorial].
J Clin Endocrinol Metab, 82 (1997), pp. 1701-1703
[29.]
Recommendations on iodine nutrition for mothers and infants in Europe. En: Delange F, Dunn JT, Glinoer D, editors. Iodine deficiency disorders in Europe: a continuing concern. New York: Plenum Press; 1993 p. 471-8.
[30.]
S. Ares, F. Héctor, J.Q. Escobar-Morreale, S. Durán, M.J. Presas, R. Herruzo, et al.
Neonatal hypothyroxinemia: effects of iodine intake and premature birth.
J Clin Endocrinol Metab, 82 (1997), pp. 1704-1712
[31.]
S. Ares, G. Morreale de Escobar, J. Quero.
Lactancia artificial y deficiencia de yodo en el niño premature.
An Esp Ped, (1999), pp. 47-51
[32.]
J. Rogahn, S. Ryan, J. Wells, B. Fraser, C. Squire, N. Wild, et al.
Randomised trial of iodine intake and thyroid status in preterm infants.
Arch Dis Child Fetal Neonatal Ed, 83 (2000), pp. F86-F90
[33.]
J.M. Mandel, R.J. Hermos, C.A. Larson, A.B. Prigozhin, D.A. Rojas, M.L. Mitchell.
Atypical hypothyroidism and the very low birthweight infant.
Thyroid, 10 (2000), pp. 693-695
[34.]
M.H. Connors, D.M. Styne.
Transient neonatal “athyreosis” resulting from thyrotropin-binding inhibitory immunoglobulins.
Pediatrics, 78 (1986), pp. 287-290
[35.]
F. Calaciura, G. Miscio, A. Coco, D. Leonardi, C. Cisternino, C. Regalbuto, et al.
Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach.
Thyroid, 12 (2002), pp. 945-951
[36.]
H. Krude, H. Biebermann, D. Schnabel, P. Ambrugger, A. Grüters.
Molecular pathogenesis of nenatal hypothyroidism.
Horm Res, 53 (2000), pp. 12-18
[37.]
A. Grütters, H. Biebermann, H. Krude.
Neonatal thyroid disorders.
Horm Res, (2003), pp. 24-29
[38.]
J.J.M. De Viljder.
Primary congenital hypothyroidism: defects in iodine pathways.
Eur J Endocrinol, 149 (2003), pp. 247-256
[39.]
H. Fagman, M. Grande, A. Gritli-Linde, M. Nilsson.
Genetic deletion of sonic hedgehog causes hemigenesis and ectopic development of the thyroid in mouse.
Am J Pathol, 164 (2004), pp. 1865-1872
[40.]
P. Schrumpf, N. Haufs, G. Schwabe, S. Mundios, A. Grüters, H. Krude.
Disturbed co-development of thyroid gland and cervical arteries as a new model for thyroid dysgenesis [resumen].
Horm Res, 62 (2004), pp. 7
[41.]
R.J. Clifton-Bligh, J.M. Wentworth, P. Heinz, M.S. Crisp, R. John, J.H. Lazarus, et al.
Mutations of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia.
Nature Gen, 18 (1998), pp. 399-401
[42.]
P.E. Macchia, P. Lapi, H. Krude, M.T. Pirro, C. Missero, L. Chiovato, et al.
PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis.
Nature Gen, 19 (1998), pp. 83-85
[43.]
T. Congdon, L.Q. Nguyen, C.R. Nogueira, R.L. Habiby, G. Modeiros-Neto, P. Kopp.
A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: Evidence for phenotypic variability in mother and child.
J Clin Endocrinol Metab, 86 (2001), pp. 3962-3967
[44.]
G. Damante.
Thyroid defects due to PAX8 gene mutations.
Eur J Endocrinol, 139 (1998), pp. 563-566
[45.]
P. Lapi, P.E. Macchia, L. Chiovato, E. Biffali, L. Moschini, D. Larizza, et al.
Mutations encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis.
Thyroid, 7 (1997), pp. 383-387
[46.]
M.G. Perna, D. Civitareale, V. De Filippis, M. Sacco, C. Cisternino, V. Tassi.
Absence of mutations in the gene encoding thyroid transcription factor (TTF-1) in patients with thyroid disgenesis.
Thyroid, 7 (1997), pp. 377-381
[47.]
K. Devriendt, C. Vanhole, G. Matthils, F. De Zegher.
Deletion of thyroid transcription factor-1 in an infant with neonatal thyroid dysfunction and respiratory failure.
N Engl J Med, 338 (1998), pp. 1317-1318
[48.]
S. Guazzi, M. Price, M. De Felice, G. Damante, M.G. Mattei, R. Di Lauro.
Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays novel DNA binding specificity.
EMBO J, 9 (1990), pp. 3631-3639
[49.]
S. Kimura, Y. Hara, T. Pineau, P. Fernández-Salguero, C.H. Fox, J.M. Ward, et al.
The t/erp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain and pituitary.
Gens Dev, 10 (1996), pp. 60-69
[50.]
A. Hishinuma, T. Kuribayashi, Y. Kanno, K. Onigata, K. Nagashima, T. Ieiri.
Sequence analysis of thyroid transcription factor-1 gene reveals absence of mutations in patients with thyroid dysgenesis but presence of polymorphisms in the 5’ flanking region and intron.
Endocr J, 45 (1998), pp. 563-567
[51.]
J.G. Seidman, C. Seidman.
Transcription factor haploinsufficiency: when half a loaf is not enough.
J Clin Invest, 109 (2002), pp. 451-455
[52.]
C. Li, J. Cai, Q. Pan, P. Minoo.
Two functionally distinct forms of NKX2.1 protein are expressed in the pulmonary epithelium.
Biochem Biophys Res Comun, 270 (2002), pp. 462-468
[53.]
N. Iwatani, H. Mabe, K. Devrient, M. Kodama, T. Müke.
Deletion of NKX2.1 encoding thyroid transcription factor-1 un two siblings with hypothyroidism and respiratory failure.
J Pediatr, 137 (2000), pp. 272-276
[54.]
H. Krude, B. Schütz, H. Biebermann, A. Von Moers, D. Schnabel, H. Neitzel, et al.
Choreoathetosis, hypothyroidism and pulmonary alterations due to human NKX2.1 haploinsufficiency.
J Clin Invest, 109 (2002), pp. 475-480
[55.]
H. Krude, H. Biebermen, H. Jung, T. Lafferty, P. Bergmann, A. Grüters.
NKX2-1/TTF-1 mutations beyond the thyroid: the extended phenotype, evidence for dominant transmission and new cases.
Horm Res, 58 (2002), pp. 12-13
[56.]
J. Pohlenz, A. Dumitrescu, D. Zundel, U. Martiné, W. Schönberger, E. Koo, et al.
Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice.
J Clin Invest, 109 (2002), pp. 469-473
[57.]
E. Vicens-Calvet, G. Pérez de Narclaes, N. Potau, J.R. Bilbao, A. Carrascosa, P. Martul, et al.
Two sisters with choreoathetosis and hypothyroidism due to human NKX2.1 haploinsuficiency [resumen].
Horm Res, 60 (2003), pp. 110
[58.]
A.F. Haerer, R.D. Currier, J.F. Jackson.
Hereditary non-progressive chorea of early onset.
Neurology, 16 (1966), pp. 307-310
[59.]
G.J. Breedveld, J.W.F. Van Dongen, C. Danesino, A. Guala, A.K. Percy, L.S. Dure, et al.
Mutations in TITF-1 are associated with benign hereditary chorea.
Hum Mol Genet, 11 (2002), pp. 971-979
[60.]
B.BA. De Vries, W.F.M. Arts, G.J. Breedveld, J.J.M. Hoogeboom, M.F. Niermeijer, P. Heutink.
Benign hereditary chorea of early onset maps to chromosome 14q.
Am J Human Genet, 66 (2000), pp. 136-142
[61.]
R. Pasckhe, M. Ludgate.
The thyrotropin receptor in thyroid diseases.
N Engl J Med, 337 (1997), pp. 1675-1681
[62.]
M.J. Abramowics, L. Duprez, J. Parma, G. Vassart, C. Heinrichs.
Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hipoplasia of the thyroid gland.
J Clin Invest, 99 (1997), pp. 3018-3024
[63.]
N. Gagné, J. Parma, C. Deal, G. Vassart, G. Van Vliet.
Apparent congenital athyreosis contrasting with norml plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities.
J Clin Endocrinol Metab, 83 (1998), pp. 1771-1775
[64.]
A. Jordan, N. Williams, J.W. Gregory, C. Evans, M. Owen, M. Ludgate.
The W546X mutation of the thyrotropin receptor gene: Potential major contributor to thyroid dysfunction in a Caucasian population.
J Clin Endocrinol Metab, 88 (2003), pp. 1002-1005
[65.]
E. Mayayo, P. Santisteban, E. Vicens-Calvet.
Patología tiroidea fetal y neonatal.
Tratado de endocrinología pediátrica y de la adolescencia, 2.ª ed., pp. 647-700
[66.]
G. Dai, O. Levy, N. Carrasco.
Cloning and characterization oh the thyroid iodide transporter.
Nature, 379 (1996), pp. 458-459
[67.]
H. Fujiwara, K. Tatsumi, K. Miki, T. Harada, K. Miyai, S. Takai, et al.
Congenital hypothyroidism caused by a mutation in the Na+/I- symporter.
Nature Genet, 16 (1997), pp. 124-125
[68.]
S.M. Kaminsky, O. Levy, C. Salvador, G. Dai, N. Carrasco.
Na+/I symporter activity is present in membrane vesicles from thyrotpropin- deprivated non -I --transporting cultured thyroid cells.
Proc Natl Acad Sci USA, 91 (1994), pp. 3789-3793
[69.]
A. Matsuda, S. Kosugi.
A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect.
J Clin Endocrinol Metab, 82 (1997), pp. 3966-3971
[70.]
T. Kogai, T. Endo, T. Saito, A. Miyazaki, A. Kowaguchi, T. Onaya.
Regulation by thyroid-stimulating hormone of sodium/iodid? symporter gene expression and protein levels in FRTL cells.
Endocrinology, 138 (1997), pp. 2227-2232
[71.]
K. Ryu, Q. Tong, S. Jhiang.
Promoter characterization of the human Na+/I symporter.
J Clin Endocrinol Metab, 83 (1998), pp. 3247-3251
[72.]
P.H.K. Eng, G.R. Cardona, M. Previti, W.W. Chin, L.E. Braverman.
Regulation of the sodium iodide symporter by iodide in FRTL-5 cells.
Eur J Endocrinol, 144 (2001), pp. 139-144
[73.]
S. Kosugi, H. Okamoto, A. Tamada, F. Sánchez-Franco.
A novel peculiar mutation in the sodium/iodide symporter gene in Spanish siblings with iodide transport defect.
J Clin Endocrinol Metab, 87 (2002), pp. 3830-3836
[74.]
A.M. Rodríguez, B. Peron, L. Lacroix, B. Caillou, G. Leblanc, M. Schulumberger, et al.
Identification and characterization of a putative human iodide transport located at the apical membrane of thyrocites.
J Clin Endocrinol Metab, 87 (2002), pp. 3500-3503
[75.]
B. Bakker, H. Bikker, T. Vulsma, J.S.E. De Randamie, M. Wiedijk, J.J.M. DeVijlder.
Two decades of screening of congenital hypothyroidism in the Nederlands: TPO gene mutations in total iodide organification defects (an update).
J Clin Endocrinol Metab, 85 (2000), pp. 3708-3712
[76.]
M.J. Abramowicz, H.M. Targovnik, V. Varela, P. Cochaux, L. Krawiec, M.A. Pisarev, et al.
Identification of a mutation in the coding sequence of the human thyroid peroxidase gene causing congenital goiter.
J Clin Invest, 90 (1992), pp. 1200-1204
[77.]
C.L.S. Santos, H. Bikkert, K.G.M. Rego, A. Nascimento, M. Tambascia, J.J.M. De Vijlder, et al.
A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect.
Clin Endocrinol (Oxf), 51 (1999), pp. 165-172
[78.]
J.J.M. De Viljder, T. Vulsma.
Hereditary metabolic disorders causing hypothyroidism.
The thyroid: a fundamental and clinical text, 8th ed., pp. 733-742
[79.]
J.C. Moreno, H. Bikker, M.J.E. Kempers, P. Van Trotsenburg, F. Baas, J.J.M. Vijlder, et al.
Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism.
N Engl J Med, 347 (2002), pp. 95-1002
[80.]
L. Fugazzola, D. Mannavola, N. Cerutti, M. Maghine, F. Pagella, P. Bianchi, et al.
Molecular analysis of the Pendred's syndrome gen and magnetic resonance imaging studies of the inner ear are essential for the diagnosis of true Pendred's syndrome.
J Clin Endocrinol Metab, 85 (2000), pp. 2469-2475
[81.]
A.M. Yong, S.S. Goh, Y. Zhao, P.H.K. Eng, L.K.H. Koh, D.H.C. Khoo.
Two Chinese families with Pendred's syndrome-radiological imaging of the ear and molecular analysis of the Pendrin gen.
J Clin Endocrinol Metab, 86 (2001), pp. 3907-3911
[82.]
O. González-Trevino, O.K. Arseven, C.J. Ceballos, V.I. Vives, R.C. Ramírez, V.V. Gómez, et al.
Clinical and molecular analysis of three Mexican families with Pendred's syndrome.
Eur J Endocrinol, 144 (2001), pp. 585-593
[83.]
A. Grüters, R. Finke, H. Krude, H. Meinhold.
Etiological grouping of permanent congenital hypothyroidism with thyroid gland in situ.
Horm Res, 41 (1994), pp. 3-9
[84.]
T. Ieiri, P. Cochauux, H.M. Targovnik, M. Suzuki, S. Shimoda, J. Perret, et al.
A 3’ splice site mutation in the thyroglobulin gene responsible for congenital goiter with hypothyroidism.
J Clin Invest, 88 (1991), pp. 1901-1905
[85.]
H.M. Targovnik, V. Varela, G.D. Frechtel, G.E. Cerrote, S.E. Copelli, F.V. Propato, et al.
Molecular genetics of hereditary thyroid diseases due to a defect in the thyroglobulin or thyroperxidases synthesis.
Braz J Med Biol Res, 27 (1994), pp. 2745-2757
[86.]
H.M. Targovnik, G. Madeiros-Neto, V. Varela, P. Cochaux, B.L. Wajchenberg, G. Vassart.
A nonsense mutation causes human hereditary congenital goiter with preferential production of a 171-nucleotide-deleted thyroglobulin ribonucleic acid messenger.
J Clin Endocrinol Metab, 77 (1993), pp. 210-215
[87.]
S.A.R. Van de Graaf, C. Ris-Talpers, G.J.M. Veeboer, M. Cammenga, C. Santos, H.M. Targovnik, J.M. Vijlder, et al.
A premature stopcodon in thyroglobulin messenger RNA results in familial goiter and moderate hypothyroidism.
J Clin Endocrinol Metab, 84 (1998), pp. 2537-2542
[88.]
P. Caron, C.M. Moya, D. Malet, V.J. Gutnisky, V. Chabarde, C.M. Rivolta, et al.
Compound heterozygous mutations in the thyroglobulin gene (1143delC and 6725G→A [R2223H]) resulting in fetal goitrous hypothyroidism.
J Clin Endocrinol Metab, 88 (2003), pp. 3546-3553
[89.]
A. Acebron, P. Aza-Blanc, D.L. Rossi, L. Lamas, P. Santisteban.
Congenital human thyroglobulin defect due to low expression of the thyroid-specific transcriptor factor TTF-1.
J Clin Invest, 96 (1995), pp. 781-785
[90.]
G. Madeiros-Neto, P.S. Kim, S.E. Yoo, J. Vono, H.M. Targovnik, R. Camargo, et al.
Congenital hypothyroid goiter with deficient thyroglobulin. Identification of an endoplasmic reticulum storage disease with induction of molecular chaperones.
J Clin Invest, 98 (1996), pp. 2838-2844
[91.]
J. Corral, C. Martín, R. Pérez, I. Sánchez, M.T. Mories, J.L. San Millán, et al.
Thyroglobulin gene point mutation associated with non-endemic simple goiter.
Lancet, 341 (1993), pp. 462-464
[92.]
C. Pérez-Centeno, R. González-Sarmiento, M.T. Mories, J. Corral, J.M. Miralles-García.
Thyroglobulin exon 10 gene point mutation in a patient with endemic goiter.
Thyroid, 6 (1996), pp. 423-427
[93.]
R. González-Sarmiento, J. Corral, M.T. Mories, J.J. Corrales, E. Miguel- Velado, J.M. Miralles-García.
Monoalelic deletion in the 5’ region of the thyroglobulin gene as a cause of sporadic nonendemic simple goiter.
Thyroid, 11 (2001), pp. 789-793
[94.]
H.J. Hirsch, S. Shilo, I.M. Spitz.
Evolution of hypothyroidism in familial goiter due to deiodinase deficiency? report of a family and review of the literature.
Post Med J, 62 (1986), pp. 477-480
[95.]
F. Ismail-Beigi, M. Rahimoifar.
A variant of iodotyrosine-desahalogenase deficiency.
Clin Endocrinol Metab, 44 (1997), pp. 499-506
[96.]
N. Kleinhaus, J. Faber, L. Kahana, J. Schneer, M. Scheinfeld.
Euthyroid hyperthyroxinemia due to generalized.5’-deiodinase defect.
Clin Endocrinol Metab, 66 (1988), pp. 684-688
[97.]
J.C. Moreno, R. Keijser, D. Gestel, L. Gijhuis-Pederson, J.J.M. Vijdler, C. Ris-Stapers.
Cloning and characterization of the human thyroid dehaloganase [resumen].
Horm Res, 60 (2003), pp. 2
[98.]
S. Gnidehou, B. Caillou, M. Talbot, R. Ohayon, J. Kaniewski, M.S. Noel-Hudson, et al.
Iodotyrosine dehalogenase (DEHAL1) is a transmembrane protein involved in the recycling of iodide close the thyroglobulin iodination site.
FASEB J, 18 (2004), pp. 1574-1576
Copyright © 2005. Sociedad Española de Endocrinología y Nutrición
Opciones de artículo
Herramientas
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos