Familial thyroid hormone resistance

Abstract

Three phenotypically normal family members were discovered to have elevated thyroid function (T4, free T4, T3, 123I uptake), but were clinically euthyroid. Further evaluation of pituitary and peripheral indices of thyroid hormone action was consistent with the diagnosis of peripheral resistance to thyroid hormone. Basal metabolic rate, serum cholesterol, pulse wave arrival time (QKd), and serum sex hormone binding globulin levels were all normal. Serum TSH was inappropriately elevated for the degree of thyroid hormone excess, while serum alpha subunit levels were normal. TSH responses to TRH (200 micrograms) were commensurate with the basal TSH levels, and decreases in TSH were observed after T3, dexamethasone, and bromocriptine administration. Analysis of thyroid hormone binding to an extract of mononuclear leukocyte nuclei disclosed no abnormalities. The reason for these patients' resistance to thyroid hormones remains to be elucidated. The proper diagnosis of this syndrome may be difficult. Assessment of pituitary TSH secretory dynamics and peripheral indices of thyroid hormone action should be performed in all hyperthyroxinemic patients who do not have obvious symptoms and signs of thyrotoxicosis.