Graves’ Disease Associated with Elevated Serum Thyroxine-Binding Globulin Concentrations*

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Abstract
Eleven cases of Graves’ disease associated with levated levels of T4-binding globulin (TBG) were examined. The patients consisted of 10 women and 1 man, none of whom was pregnant or receiving estrogenic drugs. Their liver functiontests were normal, except for elevated values of alkaline phosphatase. In the euthyroid state after herapy, total T1 values 10.6 ± 0.8 μg /dl (mean ± SD)] were in the upper normal range (5.073–11.0 μg/dl) and total Ta values (210± 49 ng/dl) were above he normal range (110–200 ng/dl). On the other hand, values of T3uptake (20.4 ±2.1%) were decreased (normal range, 23–34%),and TBG values (40.1 ± 4.8 μg/ml) were more than 3 SD above the mean of normal subjects (19.2 ±4.8 jug/ml in men and 22.7 ± 4.4 μg/ml in women). The mean (±SD) results of the thyroid function tests in the patients before therapy were as follows: total Ty3 20.6 ±2.9 jug/ dl; total T3 406 ±91 ng/dl; T3 uptake, 32.5 ± 5.5%; T, to T4 ratio, 19.5 ± 4.3 ng/g (>20 in untreated cases of Graves’ disease); and TBG, 29.6 ± 2.8 /g/ml. In untreated thyrotoxic patients with Graves’ disease, the TBG concentration was inversely correlated with the T3 to T1 ratio (r = −0.54; P < 0.001). Therefore, levated TBG levels could be predicted from the low values of the T3 to T4 ratio before therapy in 6 of the 11 patients. Examination of the 7 families of 8 cases revealed familial TBG excess in 5 families. Findings in 3 of these families were compatible with X-linked inheritance of TBGexcess. Elevated TBG in Graves’ disease is not a rare phenomenon. It is important to recognize such cases in the early thyrotoxic stage of the disease to avoid overmedication. The possible relation of Graves’ disease to an elevated TBG level is discussed.(J Clin Endocrinol Metab51: 325, 1980)