Familial dysalbuminemic hyperthyroxinemia (FDAH) is an autosomal dominant condition characterized by the presence of a variant serum albumin with preferential affinity for thyroxine (T4) in clinically euthyroid individuals. Individuals have consistently elevated total T4 and elevated or normal free T4 values with normal TSH levels. FDAH is the most commonly inherited euthyroid hyperthyroxinemia in Caucasian populations with an estimated prevalence of 1 in 10,000 individuals. The condition does not cause disease since the concentration of free hormone is normal, but affected individuals may be at risk for unnecessary laboratory testing and possibly even inappropriate treatment (summary by Heufelder et al., 1995 and Kragh-Hansen et al., 2017).

A rare genetic disease with characteristics of childhood onset of multiple endocrine manifestations in combination with central and peripheral nervous system abnormalities. Reported signs and symptoms include postnatal growth retardation, moderate intellectual disability, hypogonadotropic hypogonadism, insulin-dependent diabetes mellitus, central hypothyroidism, demyelinating sensorimotor polyneuropathy, cerebellar and pyramidal signs. Progressive hearing loss and a hypoplastic pituitary gland have also been described. Brain imaging shows moderate white matter abnormalities.

Abnormal thyroid hormone metabolism-3 (THMA3) is characterized by euthyroid hyperthyroxinemia, with elevated free T4 and reverse T3 levels, and normal TSH (see 188540) and free T3 levels. Patients also show low plasma selenium levels and reduced levels of stress-related selenoproteins (Schoenmakers et al., 2016; Geslot et al., 2021). For a discussion of genetic heterogeneity of abnormal thyroid hormone metabolism, see THMA1 (609698).