A new TRβ mutation in resistance to thyroid hormone syndrome

Abstract

thyroid hormones (tH) exert their actions by binding nuclear receptors alpha (trα1) and beta (Trß1 and Trß2). resistance to thyroid hormone (rTh) is a clinical syndrome with various clinical manifestations, its hallmark being decreased tissue sensitivity to the action of thyroid hormones. we report the case of a family harbouring a novel Trß mutation. sequencing of the trβ gene revealed a single nucleotide substitution-c to G in codon 340: glutamine was replaced by glutamic acid. The clinical picture and biochemical and hormonal panel showed significant differences within the family, despite their sharing the same mutation. we also present the result of low-dose antithyroid treatment in one member of the family diagnosed with this rare condition.

Challenging diagnosis of resistance to thyroid hormone in a patient with pituitary adenoma

“…Other tests like α-subunit/TSH ratio, T3 suppression test and thyroid hormone reduction during long-acting somatostatin analogue can also be useful to the differential diagnosis between TSHoma and RTH-beta. There are also other few cases described of RTH and pituitary adenomas,5 some with positive immunoreactivity to TSH, suggesting the presence of TSHoma 8–11. Somatic mutations in the THRB gene have been identified in some TSHomas, suggesting that defective thyroid receptor may interfere with the negative feedback of TSH, and eventually subsequent pituitary tumour development 6.…”

Reduced pituitary size in subjects with mutations in the THRB gene and thyroid hormone resistance

“…Literature shows that up to 15% of healthy people may have a small, clinically inapparent pituitary adenoma 6 . Cases of RTH and incidental pituitary adenomas 23,24 , or pituitary hyperplasia (in contrast to a reduced pituitary size) 25,26 have been reported. Regression of pituitary enlargement following thyroxine therapy in a patient with RTHbeta can occur 27 .…”

Update on resistance to thyroid hormone syndromeβ

“…TR-α1 is widely distributed, particularly in the heart and muscle tissue, while TR-α2 is widely distributed but unable to bind hormones. TR-β1 is mainly distributed in the brain, liver and kidney, whereas TR-β2 is mainly expressed in the hypothalamus and pituitary gland [12,13].…”