Dysprealbuminemic hyperthyroxinemia in a patient with hyperthyroid graves disease

Rare mutant forms of circulating albumin and prealbumin [transthyretin (TTR)] have increased binding affinity for thyroxine (T ₄). Patients with these variant plasma proteins, as a result of inherited mutations or as a paraneoplastic phenomenon, typically present with increased serum total T ₄ and, by some assay methodologies, an increased free T ₄ as well. Although these individuals are, in fact, euthyroid, nonspecific symptoms may lead to inappropriate treatment for hyperthyroidism. We present a 34-year-old woman in whom a mutant form of TTR with increased T ₄ binding affinity and coexisting Graves disease was present. Subsequent ¹³¹I therapy led to development of postablative hypothyroidism, which was obscured by her higher serum free T ₄ concentration. Circulating thyroid-binding globulin (TBG), albumin, and TTR concentrations were all within their respective reference limits. A T ₄-binding protein panel confirmed that TTR-bound T ₄ was significantly increased, whereas TBG- and albumin-bound T ₄ was normal, indicating that this patient had euthyroid dysprealbuminemic hyperthyroxinemia, which had been masked by the initial presentation of hyperthyroidism. These findings indicate that hypothyroidism can be masked by coexisting euthyroid dysprealbuminemic hyperthyroxinemia.