Genetics and clinical significance of thyroxine binding globulin deficiency, an analysis of seven families.

Seven families, ascertained through probands with undetectable levels of thyroxine binding globulin (TBG) were studied from clinical and genetic points of view. The blood levels of TBG, thyroxine binding prealbumin (TBPA), thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were determined in altogether 128 family members. The concentration of free thyroxine (FT4) was calculated from the concentrations of T4, TBG and TBPA. Only men (n = 15) were found to have total TBG deficiency. Their TSH levels were within normal range and they did not show any clinical symptoms of thyroid dysfunction. The mothers and daughters of the affected men had significantly lower TBG levels than control women. Segregation analysis performed on 46 nuclear families showed significant evidence for an X-linked additive mode of transmission and an additional multifactorial component with heritability 0.47.