NORMALLY, the bulk of total serum thyroxine (T4), approximately 80 per cent, is bound to T4-binding globulin, a glycoprotein synthesized in the liver. An elevation in the serum concentration of this protein that is genetic in origin and unrelated to stimulators such as estrogens was initially recognized in 1959 to cause hyperthyroxinemia. At least 12 kindreds with this disorder have since been described in the literature.123456 Although autosomal dominant inheritance was originally suggested, subsequent studies have demonstrated an X-linked mode of inheritance.23456 On routine laboratory testing, this harmless genetic abnormality is suggested by an increased level. © 1983, Massachusetts Medical Society. All rights reserved.