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  • Title: Hyperthyroxinemia due to the coexistence of two raised affinity thyroxine-binding proteins (albumin and prealbumin) in one family.
    Author: Lalloz MR, Byfield PG, Goel KM, Loudon MM, Thomson JA, Himsworth RL.
    Journal: J Clin Endocrinol Metab; 1987 Feb; 64(2):346-52. PubMed ID: 3098776.
    Abstract:
    The T4-binding proteins of a euthyroid subject with persistent hyperthyroxinemia (T4, greater than 20 micrograms/dl) were present in normal concentrations. Abnormal transport of both T4 and rT3 was demonstrated by reverse flow paper electrophoresis; excess T4 was bound to albumin and prealbumin, while increased binding of rT3 was confined to prealbumin. The three T4-binding proteins in the serum of the subject were isolated by affinity chromatography and characterized. Equilibrium dialysis experiments demonstrated a 20-fold increase in affinity of the albumin for T4 (Ka, 5.1 X 10(6) M-1) and a 4-fold increase in affinity of prealbumin for T4 (Ka, 3.0 X 10(8) M-1); T4-binding globulin affinity was normal. Nine other members of the family were also studied. Two sisters of the propositus have both the abnormal albumin and the variant prealbumin, while a brother has normal T4-binding proteins. The mother has the abnormal albumin alone. The father, his sister, and one of his three brothers have the variant prealbumin only. Despite the presence of the variant prealbumin in some of the paternal relatives of the propositus, their total iodothyronine concentrations were within the normal ranges; the condition may, therefore, often go undetected. The characteristics of the albumin found in the affected members of this kindred are those we have defined for familial dysalbuminemic hyperthyroxinemia type I, which is inherited as an autosomal dominant trait. The pattern of inheritance of the variant prealbumin is also consistent with a dominant mode with strong penetrance. The presence of two separately inherited abnormal T4 transport proteins in the same family suggests that both conditions may be more common than has been thought.
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