Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor beta gene (THRB) and exon 7 of the albumin gene (ALB). We found 56THRBvariants (i.e., 38% of the 303 index cases, called RTH beta group). Among the samples screened for FDH variants, 18% had the variant R218H inALB(FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTH beta group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTH beta patients. Clinically, patients with FDH had fewer symptoms than patients with RTH beta. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay.