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Friday, 29 November 2013

Thyroid Disease : Thyroid hormone resistance syndrome – The Causes and Risk Factors

Thyroid disease is defined as a condition of malfunction of thyroid. Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones. Hypothyroidism is a condition in which the thyroid gland is under active and produces very little thyroid hormones. Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
Thyroid hormone resistance syndrome
Thyroid hormone resistance syndrome is defined as a condition of which affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues(a).
B. The Causes and Risk Factors
B.1. Causes
Genetic mutation
Thyroid hormone resistance occurs when a genetic mutation in the thyroid hormone receptor leads to reduced hormone binding affinity; the concentration of free thyroid hormone in the circulation is inversely correlated with the hormone binding affinity of the mutant receptor(6), such as mutation in the THRbeta gene, A317T(7) and E333D(8). According to the study of Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination by the University of Chicago, Mutations in MCT8 and SECISBP2 have also been associated with this condition(9) and a patient with the unusual coincidence of two rare congenital disorders, lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH), resulting in impaired thyroid hormone production and action, respectively(10). Thyroid hormone resistance syndrome affect approximately 1 in 40,000 live births and of of which over 100 different mutations have been identified.
B.2. Risk factors
1. Dominant inheritance
Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone. To date, all individuals expressing the RTH phenotype have been found to harbor mutations in the thyroid hormone receptor beta (TR beta) gene that impair T3-mediated function(11). Others reported a baby at age 70 days, an R243W mutation in thyroid hormone receptor β was detected in our patient; while absent in his mother, the mutation was present in his father, who never showed any symptoms(12).
2. Graves’ disease
Resistance to thyroid hormone is a syndrome caused by thyroid hormone receptor β mutations, which are usually inherited in an autosomal-dominant pattern. There is a report of a resistance to thyroid hormone in a neonate presenting with hyperthyroid symptoms born to a mother with Graves’ disease and treated with methimazole and iodine(12).
3. Minor alterations at the DNA level
Mutations in the thyroid hormone receptor (TR) beta gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRbeta gene, all others have been demonstrated to have minor alterations at the DNA level, according to the study by the Stoke Mandeville Hospital(13).
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Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/8475937
(7) http://www.ncbi.nlm.nih.gov/pubmed/19227423
(8) http://www.ncbi.nlm.nih.gov/pubmed/17177139
(9) http://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract
(10) http://www.ncbi.nlm.nih.gov/pubmed/16053391
(11) http://www.ncbi.nlm.nih.gov/pubmed/8954015
(12) http://www.ncbi.nlm.nih.gov/pubmed/22905724
(13) http://www.ncbi.nlm.nih.gov/pubmed/17132274