Introduction: Resistance to thyroid hormones (RTH) is a genetic disorder caused in 85% of cases by mutations in thyroid hormone receptor beta gene (TRβ). The current information about it in Spanish population is scarce, limited to case reports or short series of patients. Thus, we aimed to describe the clinical, biochemical and genetic features of Mediterranean patients with RTH referred to our institution (one of the referral centres in Spain) for genetic testing during the last 15 years.
Material and methods: One hundred and sixty-six blood samples of Mediterranean patients (164 Spanish and 2 Greek patients) were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9 and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals.
Results: In all, mutations were identified in 49 patients (28 probands and 21 relatives). 64.6% were women, and mean age at diagnosis among probands was 33.2±20.5 years. The following clinical features were recorded: goitre in 50%, hyperkinetic behaviour in 32%, and tachycardia in 29%. Up to 19% of the probands had suffered some type of ablative therapy (radioiodine or thyroidectomy) before diagnosis. As for biochemical features, mean TSH was 10.2±21.5 mUI/l (NV 0.44 mUI/l), and mean fT4 was 2.75±0.9 ng/dl (NV 0.82 ng/dl). We found seven new mutations not previously described: p.Ile276del, p.Arg320Ser, p.Phe451Leu, p.Pro452Arg, p.Leu456fsx9, p.Glu457Gly and p.Phe459Leu. The most frequent mutation in our population was p.Arg243Gln, present in three families. Surprisingly, none of our patients harboured the mutation p.Arg338Trp, which is the most common in the published series.
Conclusions: Clinical and biochemical features of our sample of Mediterranean population with RTH are similar to those previously described in the medical literature. However, genetic findings differ, with the identification of seven new mutations in TRβ gene.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology