Absence of Thyroid-Binding Immunoglobulins in Patients with Thyrotropin-Mediated Hyperthyroidism*

Hyperthyroid patients with elevated serum concentrations of TSH despite high circulating levels of T4 and/or T3 have recently been described. To establish further that these patients have a disorder distinct from Graves’disease, immunoglobulins that inhibit binding to human thyroid membranes (TBI) have been measured in the serum of 13 such patients (7 men and 6 women), 7 of whom had pituitary tumors. Serum TSH concentrations ranged from 1.7–160 /xU/ml while the patients were hyperthyroid. TBI were also measured in the serum of 21 normal individuals and 14 hyperthyroid patients with apparent Graves’ disease; serum TSH concentrations were less than 0.5 juU/ml in the hyperthyroid patients with Graves’disease. Si patients with Graves’disease had ophthalmopathy, and 2 had pretibial myxedema; no patient with inappropriate TSH secretion had ophthalmopathy or pretibia myxedema. TBI in the 21 normal individuals, normalized to 100%,ranged fro 82– 138%. Eleven of the 14 serum samples from patients with Graves' disease were positive for TBI (binding, <82%; range, 0-78%). Only 2 of 13 patients with inappropriate TSH secretion were positive for TBI The 1 patient with borderline positive TBI (binding, 76±) had negative thyroid-stimulating immunoglobulins, as measured b thyroidal cAMP stimulation. One patient had inappropriate TSH secretion coexisting with positive TBI (binding, 56±) and positive thyroid-stimulating immunoglobulins. These data provide evidence that TSH-mediated hyperthyroidism is a syndrome distinct from Graves’ disease.