Resistance to Thyroid Hormone: A Novel Mutation of the Thyroid Hormone Receptor β Gene in an Algerian Family

Abstract

Resistance to thyroid hormone (RTH) is an inherited disease transmitted in an autosomal dominant manner. The diagnosis is suspected when peripheral thyroid hormones are increased contrasting with normal or increased levels of thyroid stimulating hormone. Usually, people harboring the rare syndrome have few or no symptoms. However, in some patients signs of hyperthyroidism may be the revealing anomalies as in the following case: A 75 year-old woman was referred to our department for a benign adrenal incidentaloma. In her medical history she was treated for systemic hypertension and diabetes mellitus for 15 years. Clinical examination did not show any sign of adrenal secretion, but discovered rapid irregular cardiac rhythm with some hyperthyroidism features such as increased sweating and upper limbs and jaw tremor. Electrocardiogram showed atrial fibrillation. Hormonal assessment confirmed hyperthyroidism as FT4 levels were high (mean value: 30.2pmol/L (n= 9-23)), contrasting with non-suppressed TSH levels (13.8μU/mL (n = 0.2-4)). Cerebral magnetic resonance imaging was normal. Genetic testing revealed a new heterozygous mutation on exon 10 in the THRβ gene (c.1366T>G) compatible with RTH syndrome. Screening of her children showed the same hormonal profile in five out of ten. These results confirmed RTH and the familial character.

Association analysis of clinical phenotype and exon gene mutation locus in children with hyperthyroidism

“…Agretti P, et al (2012) [2] found a case of sporadic congenital non autoimmune hyperthyroidism caused by the mutation of the thyrotropin receptor gene p639s through genetic testing. Bellarbi D et al (2017) [3] found a new heterozygous mutation in exon 10 of the THRβ gene ((c.1366T>G)) in a patient through genetic testing, and found family features after screening her children. Rita B et al (2010) [4] through years of follow-up treatment and genetic testing of a case, sequencing of exon 10 of TSHR gene showed a new heterozygous germline I630L mutation.…”