A four generation study of familial dysalbuminemic hyperthyroxinemia: diagnosis in the presence of an acquired excess of thyroxine-binding globulin.

We have studied the largest kindred with familial dysalbuminemic hyperthyroxinemia (FDH) thus far reported, comprising thirty-three blood relations in four generations and three of their spouses. Our objective was to complement previous evidence concerning the precise mode of inheritance of FDH and to detect any other features of the disorder that had not yet been noted. Among the thirty three, there were thirteen patients with FDH, eight males and five females, in all of whom the abnormality appeared to be fully expressed. Within the kindred, no affected female has borne a female child, but transmission from female to male, male to male, and male to female has been observed. Among the offspring of individuals with FDH, the overall observed frequency of FDH in three filial generations was 12/22, or 54.5 per cent, yielding a computed penetrance ratio of 1.09. Four of the patients with FDH had been investigated for hyperthyroidism, and two of them had mistakenly been treated. Of particular interest were two women with FDH who were receiving oral contraceptives and whose serum thyroxine-binding globulin (TBG) concentrations were increased. The results of their thyroid function tests differed from those of patients with FDH whose TBG concentrations were normal and mainly suggested the presence of only a high TBG state. The diagnosis of FDH in these two patients was obscured, and probably would not have been made were it not for the present investigation, which led to the electrophoretic demonstration of increased binding of T4 by serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS)