Deficiência na Globulina de Ligação de Tiroxina: uma Revisão de Literatura
DOI:
https://doi.org/10.17921/1415-6938.2018v22n2p104-111Resumo
O hipotireoidismo congênito é classificado como a falta de hormônios tireoidianos após o nascimento, e que quando não tratado inicialmente,
contribui para o atraso acentuado do desenvolvimento e retardo mental. A ingestão adequada de iodo é necessária para a produção de hormônios tireoidianos. Visto que sua deficiência pode levar ao hipotireoidismo congênito em neonato, uma condição caracterizada, geralmente, por deficiência intelectual e nanismo, podendo ainda afetar a audição. O presente estudo teve como objetivo realizar uma revisão de literatura acerca da Hipotebegenemia e seus agravos relacionados à saúde. Hipotebegenemia doença genética, ligada ao cromossomo X e que acomete, principalmente, meninos. Ocorre por uma deficiência na proteína transportadora dos hormônios tireodianos - TBG. Para isto, realizaram-se buscas bibliográficas em bases eletrônicas, tais como: Bireme, Lilacs, SciELO, Pubmed e Periódicos Capes. Conclui-se que o hipotireoidismo subclínico na infância parece ser reversível na maioria dos casos. Contudo, os riscos de progressão desta condição não devem ser afastados, uma vez que as manifestações clínicas irão depender de determinadas condições, tal como as formas autoimunes.
Palavras chaves: Hipotireoidismo. Tireoglobulina Ligadora. Doença Genética.
Abstract
Congenital hypothyroidism is classified as the lack of thyroid hormones after birth, and when not treated initially, it contributes to marked
developmental delay and mental retardation. The ingestion of iodide it is necessary for the thyroid hormones production. Its deficiency can lead
to congenital hypothyroidism in the neonate, a condition usually characterized by intellectual deficiency and dwarfism, and may even affect hearing. The objective of the present study was to carry out a review of the literature on Hypothembemia and its health related diseases. It is a Hipotebegenemia genetic disease, linked to the X chromosome and affects mainly boys. It occurs due to a deficiency in thyroid hormone carrier protein - TBG. For this, bibliographic searches were carried out in electronic databases, such as: Bireme, Lilacs, SciELO, Pubmed and Periodicals CAPES. It is concluded that subclinical hypothyroidism in childhood seems to be reversible in most cases. However, the risks of progress by category are not required, since that the clinical manifestations will depend on conditions, such as autoimmune forms.
Keywords: Hypothyroidism. Binding Thyroglobulin. Genetic Disease.
Referências
BERNAL, J. Thyroid hormone receptors in brain development
and function. Nat. Clin. Practice Endocrinol. Metabolism., v.3,
n.3, p.249-259, 2007.
BIONDI, B.; COOPER, D.S. The clinical significance of
subclinical thyroid dysfunction. Endocrine Reviews, v.29, n.1,
p.76-131, 2008. doi: 10.1210/er.2006-0043
BROWN, R. S. Disorders of the thyroid gland in infancy, childhood
and adolescence. Dis. Thyroid, p.63-83, 2017. Disponível em:
https://www.ncbi.nlm.nih.gov/books/NBK279032/
BROWN, R.S. Autoimmune thyroiditis in Childhood. J. Clin.
Res. Pediatr. Endocrinol., v.5, n., p.45-49, 2013.
CALEBIRO, D. et al. Frequent TSH receptor genetic alterations
with variable signaling impairment in a large series of children
with nonautoimmune isolated hyperthyrotropinemia. J. Clin.
Endocrinol. Metabol., v. 97, n. 1, p.156-160, 2012.
CANARIS, G. J. et al. The colorado thyroid disease prevalence
study. Arch. Int. Med., v.160, n.4, p. 526-534, 2000.
CASSIO, A. et al. Current loss-of-function mutations in the
thyrotropin receptor gene: when to investigate, clinical effects,
and treatment. J. Clin. Res. Pediatr. Endocrinol., v.5, p.29-39,
doi: 10.4274/Jcrpe.864
CASTANET, M. et al. Nineteen years of national screening
for congenital hypothyroidism: Familial cases with thyroid
dysgenesis suggest the involvement of genetic factors. J. Clin.
Endocrinol. Metabol., v. 86, n.5, p.2009-2014, 2001.
CERBONE, M. et al. Linear growth and intellectual outcome in
children with long-term idiopathic subclinical hypothyroidism.
Eur. J. Endocrinol., v.164, n.4, p.591-597, 2011.
CERBONE, M. et al. Cardiovascular risk factors in children with
long-standing untreated idiopathic subclinical hypothyroidism.
J. Clin. Endocrinol. Metabol., v.99, n.8, p.2697-2703, 2014. doi:
1210/jc.2014-1761.
CHAKER, L. et al. Subclinical hypothyroidism and the risk of
stroke events and fatal stroke: An individual participant data
analysis. J. Clin. Endocrinol. Metabol., v.100, n.6, p.2181-2191,
doi: 10.1210/jc.2015-1438.
CHASE, H. P. et al. Thyroid Hormone Replacement and Growth
of Children with Subclinical Hypothyroidism and Diabetes.
Diabetic Med., v.7, n.4, p.299-303, 1990.
DELADOËY, J. et al. Is the incidence of congenital hypothyroidism
really increasing? A 20-year retrospective population-based study
in Québec. J. Clin. Endocrinol. Metabol., v.96, n.8, p.2422-2429,
doi: 10.1210/jc.2011-1073
DELANGE, F. Neonatal screening for congenital hypothyroidism:
results and perspectives. Hormone Res., v.48, n.2, p.51-61, 1997.
DELANGE, F. Screening for Congenital Hypothyroidism Used
as an Indicator of the Degree of Iodine Deficiency and of its
Control. Thyroid, v.8, n.12, p.1185-1192, 1998.
DUNTAS, L. H.; WARTOFSKY, L. Cardiovascular risk and
subclinical hypothyroidism: focus on lipids and new emerging
risk factors. What is the evidence? Thyroid, v.17, n.11, p.1075-
, 2007.
FERRARA, A.M. et al. A novel mechanism of inherited TBG
deficiency: mutation in a liver-specific enhancer. J. Clin.
Endocrinol. Metabol., v.100, n.1, p.E173-E181, 2015. doi:
1210/jc.2014-3490.
FÜHRER, D.; BOCKISCH, A.; SCHMID, K. W. Euthyroid goiter
with and without nodules-diagnosis and treatment. Deutsches
Ärzteblatt Int., v.109, n.29/30, p.506-515, 2012.
GIBSON, P. A et al. Longitudinal study of thyroid function in
Down’s syndrome in the first two decades. Arch. Dis. Childhood,
v.90, n.6, p.574-578, 2005.
GOPALAKRISHNAN, S. et al. Goitrous Autoimmune thyroiditis
in a pediatric population: a longitudinal study. Pediatrics, v. 122,
n. 3, p. e670–e674, 2008.
HARRIS, K. B.; PASS, K. A. Increase in congenital
hypothyroidism in New York State and in the United States.
Molecular Genetics Metabol., v.91, n.3, p.268-277, 2007.
HEGEDÜS, L.; BONNEMA, S. J.; BENNEDBÆK, F. N.
Management of simple nodular goiter: Current status and future
perspectives. Endocrine Rev., 24, n.1, p.102-132, 2003.
HORN, S.; HEUER, H. Thyroid hormone action during brain
development: More questions than answers. Mol. Cellular
Endocrinol., v.315, n.2, p.19-26, 2010.
ISHIGURO, H. et al. Long-term follow-up of thyroid function
in patients who received bone marrow transplantation during
childhood and adolescence. J. Clin. Endocrinol. Metabolism.,
v.89, n. p.5981-5986, 2004.
KARMISHOLT, J.; ANDERSEN, S.; LAURBERG, P. Variation
in thyroid function in subclinical hypothyroidism: Importance of
clinical follow-up and therapy. Euro. J. Endocrinol., 164, n. 3,
p.317-323, 2011.
KING, K.; O’GORMAN, C.; GALLAGHER, S. Thyroid
dysfunction in children with Down syndrome: a literature review.
Irish J. Med. Sci., 183, n.1, p.1-6, 2014.
LANCET, T. et al. Subclinical thyroid disease Already a Print
Subscriber ? Lancet, v.379, n.9821, p.2012-2013, 2012.
LÉGER, J. et al. Thyroid developmental anomalies in first degree
relatives of children with congenital hypothyroidism. J. Clin.
Endocrinol. Metabol., v.87, n.2, p.575-580, 2002.
LEONARDI, D. et al. Longitudinal study of thyroid function in
children with mild hyperthyrotropinemia at neonatal screening
Rev. Cienc. Gerenc., v. 22, n. 2, p. 104-111, 2018 110
BARBOSA,K.L.; ARAÚJO,C.L.F.L.
for congenital hypothyroidism. J. Clin. Endocrinol. Metabol.,
v.93, n.7, p.2679-2685, 2008.
LÖF, C. et al. Detection of Novel Gene Variants Associated with
Congenital Hypothyroidism in a Finnish Patient Cohort. J. Am.
Thyroid Assoc., v.26, n.9, p.1215-1224, 2016.
MANNAVOLA, D. et al. TGB deficiency: Description of two
novel mutations associated with complete TBG deficiency and
review of the literature. J. Mol. Med., 84, n.10, p.864-871, 2006.
MANTOVANI, G.; SPADA, A.; ELLI, F. M.
Pseudohypoparathyroidism and Gsα–cAMP-linked disorders:
current view and open issues. Nat. Rev. Endocrinol., v.12, n.6,
p.347-356, 2016. doi: 10.1038/nrendo.2016.52.
MARATOU, E. et al. Studies of insulin resistance in patients with
clinical and subclinical hypothyroidism. Euro. J. Endocrinol.,
v.160, n.5, p.785-790, 2009.
MARWAHA, R.K. et al. Dyslipidemia in subclinical
hypothyroidism in an Indian population. Clin. Biochemistr., v.44,
n.14/15, p.1214-1217, 2011.
MOELLER, L.C. et al. Two novel mutations in the gene are
associated with complete deficiency of thyroxine-binding
globulin. Euro. Thyroid J., v.4, n.1, p.108-112, 2015. doi:
1159/000381093.
MONZANI, A. et al. Endocrine disorders in childhood and
adolescence. Natural history of subclinical hypothyroidism in
children and adolescents and potential effects of replacement
therapy: a review. Euro. J. Endocrinol., v.168, n.1, p.1-11, 2013.
MORI, Y. et al. Replacement of leu227 by pro in thyroxinebinding
globulin (TBG) is associated with complete tbg
deficiency in three of eight families with this inherited defect. J.
Clin. Endocrinol. Metabol., v.70, n.3, p.804-809, 1990.
NANCHEN, D. et al. Subclinical thyroid dysfunction and the risk
of heart failure in older persons at high cardiovascular risk. J.
Clin. Endocrinol. Metabol., v.97, n.3, p.852-861, 2012.
PAI, H.C.; GONG, S.T. Subclinical thyroid disease. J. Int. Med.
Taiwan, v.24, n.6, p.469-476, 2013.
PAOLI-VALERI, M. et al. Atherogenic lipid profile in children
with subclinical hypothyroidism. Anal. Pediatr., v.62, n.2, p.1281-
, 2005.
PEARCE, S.H.S. et al. 2013 ETA Guideline: Management of
Subclinical Hypothyroidism. Euro. Thyroid J., v.2, n.4, p.215-
, 2013.
PEREZ-LOBATO, R. et al. Thyroid status and its association
with cognitive functioning in healthy boys at 10 years of age.
Euro. J. Endocrinol., v.172, n.2, p.129-139, 2015.
PERSANI, L. et al. Genetics and phenomics of hypothyroidism
due to TSH resistance. Mol. Cellular Endocrinol., 322, n.2, p.72-
, 2010.
PERSANI, L. Central hypothyroidism: Pathogenic, diagnostic
and therapeutic challenges. J. Clin. Endocrinol. Metabol., v.97,
n.9, p.3068-3078, 2012.
RABBIOSI, S. et al. Congenital hypothyroidism with eutopic
thyroid gland: analysis of clinical and biochemical features at
diagnosis and after re-evaluation. J. Clin. Endocrinol. Metabol.,
v.98, n.4, p.1395-1402, 2013.
RADETTI, G. et al. The natural history of euthyroid Hashimoto’s
thyroiditis in children. J. Pediatr., v.149, n.6, p.827-832, 2006.
RADETTI, G. et al. The natural history of the normal/mild
elevated TSH serum levels in children and adolescents with
Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a
-year follow-up. Clin. Endocrinol., v.76, n.3, p.394-398, 2012.
RAPA, A. et al. Subclinical hypothyroidism in children and
adolescents: a wide range of clinical, biochemical, and genetic
factors involved. J. Clin. Endocrinol. Metabol., v.94, n.7, p.2414-
, 2009.
REDDY, P.A. et al. High prevalence of associated birth defects in
congenital hypothyroidism. Int. J. Pediatr. Endocrinol., v.2010,
p.1-5, 2010.
REFETOFF, S. Inherited thyroxine-binding globulin
abnormalities in man. Endocrine Reviews, v.10, n.3, p.275-293,
REFETOFF, S. et al. Thyroxine-binding globulin: Organization
of the gene and variants. Hormone Res. Pediatr., v.45, n.3/5,
p.128-138, 1996.
REFETOFF, S. Abnormal thyroid hormone transport. Last
Update, 2015. Disponivel em: https://www.ncbi.nlm.nih.gov/
books/NBK285563/
ROSENE, M. L. et al. Inhibition of the type 2 iodothyronine
deiodinase underlies the elevated plasma TSH associated with
amiodarone treatment. Endocrinol. v.151, n.12, p.5961-5970,
SALERNO, M. et al. Subclinical hypothyroidism in childhood:
current knowledge and open issues. Nat. Rev. Endocrinol., v.12,
n.12, p.34-46, 2016.
SANDERS, P. et al. Crystal structure of the TSH receptor
(TSHR) bound to a blocking-type TSHR autoantibody. J. Mol.
Endocrinol., v.46, n.2, p.81-99, 2011.
SOHEILIPOUR, F. et al. First report of inherited thyroxinebinding
globulin deficiency in Iran caused by a known de novo
mutation in SERPINA7. Mol. Genetics Metabol. Reports, v.8,
p.13-16, 2016.
STIERAND, K.; RAREY, M. Drawing the PDB: Protein-ligand
complexes in two dimensions. ACS Med. Chem. Letters, v.1, n.9,
p.540-545, 2010.
TENENBAUM-RAKOVER, Y. et al. Long-term outcome of
loss-of-function mutations in thyrotropin receptor gene. Thyroid,
v.25, n. , p.292-299, 2015. doi: 10.1089/thy.2014.0311
TRUMPFF, C. et al. Mild iodine deficiency in pregnancy in
Europe and its consequences for cognitive and psychomotor
development of children: a review. J. Trace Elements Med. Biol.,
v.27, n.3, p.174-183, 2013.
TRUMPFF, C. et al. Neonatal thyroid-stimulating hormone
concentration and psychomotor development at preschool age.
Arch. Dis. Childhood, v.101, n.12, p.1100-1106, 2016. doi:
1136/archdischild-2015-310006.
VAN VLIET, G.; DELADOËY, J. Interpreting Minor variations in
thyroid function or echostructure. Treating patients, not numbers
or images. Pediatr. Clin. North Am., v.62, n.4, p.929-942, 2015.
doi: 10.1016/j.pcl.2015.04.008.
WITTE, T. et al. Association between serum thyroid-stimulating
hormone levels and serum lipids in children and adolescents: a
population-based study of german youth. J. Clin. Endocrinol.
Metabol., v.100, n.5, p.2090-2097, 2015. doi: 10.1210/jc.2014-
WU, T. et al. Subclinical thyroid disorders and cognitive
performance among adolescents in the United States. BMC
Pediatrics, v.6, n.1, p.12, 2006.
ZHANG, J. et al. Serum thyrotropin is positively correlated with
the metabolic syndrome components of obesity and dyslipidemia
in Chinese adolescents. Int. J. Endocrinol., v.2014, p.1-7,
Deficiência na Globulina de Ligação de Tiroxina: uma Revisão de Literatura
Rev. Cienc. Gerenc., v. 22, n. 2, p. 104-111, 2018
doi: 10.1155/2014/289503.
ZIMMERMANN, M. B. et al. Increasing the iodine concentration
in the Swiss iodized salt program markedly improved iodine
status in pregnant women and children: A 5-y prospective national
study. Am. J. Clin. Nutr., v.82, n.2, p.388-392, 2005.
ZIMMERMANN, M.B. Iodine deficiency in pregnancy and the
effects of maternal iodine supplementation on the offspring: a
review. Am. J. Clin. Nutr., v.89, n.2, p.668-672, 2009a.
ZIMMERMANN, M. B. Iodine deficiency. Endocr Rev, v.30, n.4,
p.376-408, 2009b.
