Familial euthyroidal hyperthyroxinemia is a 'nondisease' sometimes due to an anomaly of albumin, termed 'dysalbuminemic' (see 103600), or of transthyretin, termed 'dystransthyretinemic' or 'dysprealbuminemic.' Dysthyretinemic euthyroidal hyperthyroxinemia is secondary to an increased affinity for thyroxine (T4) by transthyretin ... Familial euthyroidal hyperthyroxinemia is a 'nondisease' sometimes due to an anomaly of albumin, termed 'dysalbuminemic' (see 103600), or of transthyretin, termed 'dystransthyretinemic' or 'dysprealbuminemic.' Dysthyretinemic euthyroidal hyperthyroxinemia is secondary to an increased affinity for thyroxine (T4) by transthyretin (summary by Moses et al., 1990).
Maxon et al. (1982) described familial elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. They interpreted this as representing an elevated threshold for the amount of free thyroxine substrate required to ... Maxon et al. (1982) described familial elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. They interpreted this as representing an elevated threshold for the amount of free thyroxine substrate required to maintain adequate T3 production from the peripheral monodeiodination of T4. Family studies supported autosomal dominant inheritance; male-to-male transmission was noted. Other forms of peripheral resistance to thyroid hormone with euthyroidism and hyperthyroxinemia appear to have a defect in the nuclear receptor for thyroid hormone (see 274300). Variation in thyroxine-binding prealbumin (transthyretin) has been observed as the basis of rare familial euthyroid hyperthyroxinemia (Moses et al., 1982). Lalloz et al. (1987) reported an extraordinary family in which 2 separately inherited abnormal T4 transport proteins were found. The proband, a girl aged 15 years at the time of investigation (the authors referred to her as the propositus), had both variant prealbumin and variant albumin, as did her 2 sisters. The mother had only the abnormal albumin and the father had only the variant prealbumin. By methods combining immunodetection with isoelectric focusing, Whitehouse et al. (1985) found few variants in thyroxine-binding prealbumin.
In the family studied by Moses et al. (1982), Moses et al. (1990) detected heterozygosity for a missense mutation in exon 4 of the TTR gene (176300.0015). Refetoff et al. (1996) (see 176300.0038) and others reported similar findings. ... In the family studied by Moses et al. (1982), Moses et al. (1990) detected heterozygosity for a missense mutation in exon 4 of the TTR gene (176300.0015). Refetoff et al. (1996) (see 176300.0038) and others reported similar findings.